Venous News 13 – January 2020

January 2020 | Issue 13

CAVA: Catheter-directed thrombolysis does not change post-thrombotic risk for iliofemoral deep vein thrombosis patients Additional ultrasound-accelerated catheter-directed thrombolysis (CDT) does not change the risk of post-thrombotic syndrome in patients with acute iliofemoral deep vein thrombosis (DVT) at one-year follow up, compared with standard therapy alone, according to findings of the CAVA trial published in November 2019 in Lancet Haematology. However, preliminary results of a post-hoc subgroup analysis suggest that if recanalisation is successful, post-thrombotic syndrome is less severe and quality of life scores are higher one year after an acute iliofemoral DVT.

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xamined in presentations by both Pascale Notten and Cees Wittens (Maastricht, The Netherlands)—winners of the best abstract session at the International Union of Phlebology chapter meeting (UIP; 25–27 August, Krakow, Poland)—results of the CAVA trial also showed a high rate of thrombotic events, mostly due to in-stent thrombosis.

Notten et al write: “Between May 2010, and September 2017, 184 patients were randomly assigned to either additional ultrasound-accelerated CDT (n=91) or standard treatment alone (n=93). Exclusion because of screening failure or early withdrawal of informed consent resulted in 77 patients in the intervention group and 75 in the standard treatment group starting allocated treatment.

“Median follow-up was 12 months (IQR 6–12).

Twelve-month post-thrombotic syndrome occurred in 22 (29%) patients allocated to additional treatment versus 26 (35%) patients receiving standard treatment alone (odds ratio 0.75 [95% CI 0.38–1.50]; p=0.42).

Major bleeding occurred in four (5%) patients in the intervention group, with associated neuropraxia or the peroneal nerve in one patient, and no events in the standard treatment group. No serious adverse events occurred. None of the four deaths (one [1%] in the intervention group vs. three [4%] in the standard treatment group) were treatment related.”

Moreover, as reported in Lancet Haematology, a total of 24 thrombotic events occurred in 20 patients.

Eighteen per cent (n=14) of patients from the intervention group developed 17 events, versus seven events in 8% (n=6) of patients from the control group (p=0.06). Of the 17 thrombotic events which were seen in the intervention group, more than 70% (12 out of 17) were due to in-stent thrombosis.

Speaking to Venous News about the findings of the CAVA trial, Notten says: “When comparing our results to the two previous large trials (CaVenT and ATTRACT), our outcomes regarding the development of post-thrombotic syndrome are similar to the ATTRACT trial and show no statistically significant difference between treatment groups as opposed to the CaVenT trial.

“With the CAVA trial, discussion regarding the role of additional catheter-directed thrombolysis in the treatment of acute iliofemoral DVT persists. Further

Pascale Notten (left) and Cees Wittens (right)

Further research, including optimising patient selection, interventional techniques, and peri-interventional treatment regimens, is essential.” research, including optimising patient selection, interventional techniques, and peri-interventional treatment regimens is essential.”

Can successful thrombolysis prevent post-thrombotic syndrome?

A subgroup analysis of the results, presented by Wittens at UIP, aimed to assess the success rate of additional ultrasound-accelerated CDT in restoring patency (to 90% or more), and its relation to the development of post-thrombotic syndrome at one year.

Wittens explained: “As the degree of residual vein occlusion correlates with the risk of post-thrombotic syndrome, it has been said that the preventative impact Continued on page 2

Raghu Kolluri:

Profile

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Dan Carradice:

The silent crisis of venous leg ulcers

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Study establishes association between reflux of lateral subdermic plexus and restless leg syndrome Reflux of the lateral subdermic plexus could be closely related to the symptoms of restless leg syndrome and nighttime cramping, according to a review conducted on prospective symptom tracking and patient outcomes at The Vein Institute in Rochester, New York, USA. Patients suffering from conditions such as restless leg syndrome frequently present with symptoms of chronic venous insufficiency, but no specific pattern or association has been identified until now.

SPEAKING AT THE 2019 Vascular Interventional Advances conference (VIVA; 4–7 November, Las Vegas, USA), Swar Shah (Rochester General Hospital and The Vein Institute, New York, USA) explained the paradigm of restless leg syndrome to those in attendance: “Many of these patients will present with more than the classic truncal symptoms, but the restless legs will typically present with a chronic inability to find comfortable positions when sleeping at night, and night-time cramping comes with this.”

As Shah reported during his presentation, prospective symptom tracking on the standardised patient intake form began at The Vein Institute in January 2015, under the supervision of Raj Pyne (Rochester General Hospital and The Vein Institute, New York, USA). Pyne noticed that many of the patients with symptoms of these conditions demonstrated a similar distribution of varicosities or spider vein clusters (or both) with a common pattern along the lateral lower thigh, knee and calf emerging.

“This corresponds to the lateral subdermic plexus, which is a small grouping of tributary veins that drain into the Vein of Albanese and then to the deep venous system,” Shah said, highlighting the association. “Many patients who started to undergo treatment of these veins—mainly in association Continued on page 2

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January 2020 | Issue 13

Catheter-directed thrombolysis

CAVA: Catheter-directed thrombolysis does not change post-thrombotic risk for iliofemoral deep vein thrombosis patients Continued from page 1

of ultrasound-accelerated CDT might depend on its ability to achieve successful recanalisation.”

According to the preliminary analysis, recanalisation was considered successful in 53% of patients (41 out of 77) who received additional ultrasound-accelerated CDT, while a total of 75 patients in the CAVA trial received standard treatment only. Overall, postthrombotic syndrome developed in 22% of patients (n=9) from the successful thrombolysis subgroup, and 35% (n=26) of the patients from the control group (p=0.15).

Comparing the successful thrombolysis subgroup to those who underwent unsuccessful thrombolysis— post-thrombotic syndrome developed in 13 out of 36 patients (37%)—no significant difference in proportion of post-thrombotic syndrome was seen (p=0.17).

However, the severity was significantly lower in those successfully treated. Generic and disease-specific quality of life questionnaires also differed significantly between groups, favouring those who were successfully treated.

Based on the findings of the subgroup analysis, said Wittens, successful thrombolysis does result in benefits such as a lower severity of symptoms and improved quality of life for patients when considering multiple aspects. Commenting on these results, Wittens added: “The subgroup analysis shows that proper quality control of an intervention is essential to evaluate an intended treatment. Unfortunately, this trial shows that only 53% of the patients received a successful intervention.”

He concluded: “Since the preliminary subgroup analysis showed a significant improvement in clinical scores and quality of life in those successfully recanalised, the overall conclusion of the various trials should not be that early thrombus removal is not effective in achieving better clinical outcomes and that this treatment should be abandoned; it tells us that early thrombus removal actually has the capacity to limit long-term post-thrombotic morbidity, if only we are able to improve the process of patient selection and develop better interventional treatments.”

Read a commentary on CAVA from the editorsin-chief of Venous News on page 3.

Study establishes association between reflux of lateral subdermic plexus and restless leg syndrome Continued from page 1

with other typical varicose veins or coincidentally for cosmetic spider veins—experienced a significant improvement in their restless leg syndrome and nighttime cramping symptoms,” he revealed.

A proposed aetiology for restless legs was also presented by the speaker, who discussed a hypothesis for why these symptoms occur. The normal thigh component of the lateral subdermic plexus drains inferiorly towards the knee to the deep veins, while the calf component drains superiorly towards the knee. Without the aid of gravity— when patients are laying supine—Shah explained that there is impaired flow from the lateral subdermic plexus to the deep veins which, along with reflux, can Swar Shah lead to venous stasis.

“Our theory is that it is this venous stasis which causes the restless leg syndrome to develop, and we think that it may be related to iliotibial band irritation, although this theory is not borne out in the literature,” Shah commented.

In order to explore this theory further, prospective symptom tracking and patient outcomes were evaluated; this focused on patient-reported symptoms of restless legs, patient-reported symptoms of nighttime cramping and venous reflux with augmentation in the lateral subdermic plexus on venous ultrasound lasting more than 500 milliseconds.

“The spectral Doppler ultrasound findings would show a dilated lateral system (4mm with four seconds of reflux is pretty typical) and, by comparison, we would often see patients with either large varicose veins or no large varicose veins in the more standard vessels we evaluate, such as the great saphenous vein,” said Shah, who added that “in more than one patient, the great saphenous vein was non-dilated and nonrefluxing, yet there were still symptoms of restless leg syndrome”.

As a result, patients who underwent treatment with ultrasound-guided foam sclerotherapy (USGFS) were also tracked, including clinical success (defined as technical success, short-term symptom relief by 90 days, and long-term symptoms relief at one year) and any major or minor complications.

In total, 510 patients were identified between January 2015 and December 2017; 322 of these

persons (63.1%) had an abnormal lateral system based on the investigators’ criteria, while the remaining 188 patients (36.9%) had either a normal lateral system, or the system was not identified.

Focusing on the results, Shah said: “As we go to correlate the ultrasound findings with their symptoms, we start to see some patterns emerge. In patients with restless leg syndrome, 83% will have a positive ultrasound, and with patients suffering from night-time cramping symptoms, 89% will have a positive ultrasound. When you combine these results together, as restless leg syndrome and the cramping symptoms, a positive ultrasound will be present in 91% of patients with symptoms,

Our theory is that it is this venous stasis which causes the restless leg syndrome to develop, and we think that it may be related to iliotibial band irritation.” while 98% of patients without will have a negative ultrasound.”

The technical success rate was 94%. For patients who underwent USGFS, 93% (224 out of 241) reported symptom resolution at 90-day follow-up, indicating clinical success. At one year, this number was virtually unchanged at 92%, underlining that this can be “a very durable and likely permanent treatment option”.

Based on the findings of this study, Shah concluded: “We view our study as a starting point, and we would like to see a standardised, multicentre evaluation take place in the future. If this does prove to be a cause of restless leg syndrome, as we think it might be, then it would open up a new avenue for potential treatment options. Not only would it be safe and effective, but it would also be cost-effective.”

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Issue 13 | January 2020

Catheter-directed thrombolysis

Where does the CAVA trial leave early thrombus removal for iliofemoral DVT? Manj Gohel Stephen Black Comment & Analysis Results from the Dutch CAVA trial were published recently in Lancet Haematology and, at first glance, this is another trial that failed to demonstrate any meaningful benefit for early thrombus removal in patients with acute iliofemoral deep vein thrombosis (DVT).

IN CAVA, 184 participants with iliofemoral DVT were randomised to ultrasound-accelerated catheter-directed thrombolysis (CDT) or standard care alone. One-year rates of post-thrombotic syndrome (PTS) were 29% and 35% in the intervention and standard care groups respectively, a non-significant difference.

The researchers should be commended for their efforts in trying to answer a question of enormous clinical relevance and for their perseverance in completing a trial that took over seven years to recruit. However, there are important methodological flaws to raise. Twentytwo participants (12%) withdrew consent within two days of randomisation, 30% of thrombolysis interventions were stopped early, and only 45% (35/77)

of participants starting thrombolysis underwent venous stenting, with only half of patients considered to have had successfully delivered therapy. Follow-up was limited to one year and the sample size was relatively small, meaning that CAVA was underpowered to detect anything other than a large difference.

The generalisability of CAVA will be questioned, as with ATTRACT and CaVenT. Patients enrolled into these studies only constitute a small minority of the overall population presenting with iliofemoral DVT, illustrated by the fact that less than 2.5% of the screened population in ATTRACT were randomised. Inevitably, many patients with severe symptoms will not have been included due to the lack of clinician (and/

or patient) equipoise. Perhaps the bigger question relates to the technical success.

In all three randomised controlled trials (RCTs), rates of technical success and venous stenting were relatively low, which could explain poor outcomes in the intervention arms of these trials.

Conversely, the technical outcomes in these multicentre studies could be seen as more reflective of practice, rather than selected centres of excellence.

The relationship between technical success of early thrombus removal (and durable deep venous patency) and clinical outcomes does warrant further investigation, and debate on the open vein hypothesis continues as a result.

Even with the reduced rate of postthrombotic syndrome after CDT in the CaVenT trial, and the reduced rate of moderate-severe PTS in the iliofemoral DVT subgroup in the ATTRACT trial, these benefits were underwhelming and did not match the advantages perceived by the many enthusiastic advocates of these interventions. The results of the CAVA trial compound this situation.

The apparent discord between published evidence and the experience of large swathes of the clinical community creates significant challenges, particularly as the next iterations of international guidelines are likely to reflect results from published randomised trials, and are therefore unlikely to recommend widespread early thrombus removal, which is common practice in many centres.

Despite another large RCT hoping to clarify the issue, the role of early thrombus removal in the management of acute iliofemoral DVT remains as controversial as ever. Worryingly, there seem to be increasingly partisan views

EXTRACT-PE trial of aspiration thrombectomy for acute PE meets efficacy and safety endpoints A multicentre study, conducted under an investigational device exemption (IDE) from the US Food and Drug Administration (FDA), has found that aspiration thrombectomy for acute pulmonary embolism (PE) reduces RV:LV at 48 hours and achieves a low rate of major adverse events within 48 hours.

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khilesh Sista (NYU Langone Health, New York, USA), national principal investigator of the EXTRACT-PE study, presented the results at 2019 Vascular Interventional Advances conference (VIVA; 4–7 November, Las Vegas, USA).

Describing the study rationale, he said: “Systemic thrombolysis is associated with lower mortality and clinical deterioration, but higher major bleeding than anticoagulation alone in submassive or intermediate-risk PE. “Catheter-directed thrombolysis has been used as an alternative to systemic thrombolysis and has been shown to relieve right-ventricle (RV) strain,” added Sista, “but it also carries a bleeding risk because it uses a thrombolytic drug.” As a result, catheter-based aspiration thrombectomy, without thrombolytic drug administration, is considered to be a promising solution.

The objective of EXTRACT-PE, a prospective, single-arm trial, was to evaluate both the safety and efficacy of aspiration thrombectomy with the Penumbra Indigo Aspiration System, in patients with acute PE, and without the use of thrombolytic drugs. In terms of

efficacy, the primary endpoint was a reduction in RV:LV from baseline to 48 hours. The primary safety endpoint was the rate of major adverse events within 48 hours, including device-related death, major bleeding, or a composite of clinical deterioration, pulmonary vascular injury, or cardiac injury.

Outlining the eligibility criteria for the study, Sista said: “The inclusion criteria included patients with symptomatic acute PE of 14 days or less in duration, as diagnosed by computed tomography angiography (CTA), and systolic blood pressure of more than 90mmHg with evidence of an RV:LV of less than 0.9. The patient also needed to be 18 years or older.”

Key exclusion criteria included tissue plasminogen activator (tPA) administration within 14 days of the CTA, pulmonary hypertension with a peak pulmonary artery (PA) pressure of greater than 70mmHg, a high fraction of inspired oxygen (FiO2) requirement, or cardiopulmonary surgery within the last seven days.

Ultimately, 119 patients were enrolled in the study, with two populations analysed. In the intention-totreat population of all 119 patients, a primary endpoint

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for and against intervention. In reality, both perspectives have merit.

Unwavering advocates of aggressive early thrombus removal should recognise that many patients with iliofemoral DVT treated with anticoagulation alone do not develop PTS (around 50% or more in CaVenT, ATTRACT and CAVA).

Likewise, those sceptical of early thrombus removal strategies should accept that many patients with severe symptoms (most likely to benefit from thrombolysis) were not included, and superior technical and clinical outcomes from thrombus removal—than those reported in CaVenT, ATTRACT and CAVA—are feasible. Both sides can also probably agree that the outcome measures in RCTs remain suboptimal.

There are exciting technological advances for thrombus removal, with a range of pharmacomechanical thrombolysis and thrombectomy options widely available. Whether these advances can deliver better technical success and superior clinical outcomes remains to be seen. As with many areas of venous disease, the biggest challenge remains case selection. More work is needed to define specific subgroups of patients that may benefit most from aggressive thrombus removal. Until we make progress with better patient selection and clearly good technical results though, this controversy is likely to persist.

Manj Gohel is a consultant vascular and endovascular surgeon at Cambridge University Hospitals, Cambridge, UK. Stephen Black is a consultant vascular surgeon at Guy’s and St Thomas’ NHS Foundation Trust, London, UK.

was available in 113, as six did not have an RV:LV available at 48 hours. Moreover, there was a modified intention-to-treat population which excluded patients who were treated with thrombolytic drugs during the periprocedural period or an adjunctive device within 48 hours. This population, which excluded four patients who did not have an RV:LV at 48 hours, included 106 persons for whom a primary endpoint was available.

In addition to a statistically significant reduction in on-table PA pressure, which went from 49mmHg preprocedure to 44.5mmHg post-procedure (95% CI 3.0–6.4 [p<0.0001]), the primary efficacy endpoint was met, with the procedure achieving a 0.43 reduction (27.3%) in the RV:LV on average (95% CI 0.38–0.47 [p<0.0001]) after 48 hours. The same result was found across both of the patient populations analysed.

Turning his attention to the primary safety endpoint, Sista revealed that two patients experienced a total of three major adverse events within 48 hours (a rate of 1.7%); “the first patient had a groin access site bleed,” he explained, “while the second patient had haemoptysis, which was stabilised in the suite”.

However, Sista added, “The patient died 11 hours postprocedure, due to a sustained ventricular tachycardia”.

Compared to other trials, the results of EXTRACTPE correlate with SEATTLE II and FLARE in terms of the change in RV:LV, though the percentage of major adverse events within 48 hours compares favourably. In a press release, Sista commented: “The positive results of the EXTRACT-PE trial, the first prospective safety and efficacy study of the Indigo Aspiration System, are a step forward in building needed clinical evidence around catheter-based embolectomy in patients with acute pulmonary embolism.”

Issue 13 | January 2020

Conference coverage

Compression achieves short-term reduction in pain scores following venous intervention Results of a randomised controlled trial conducted at Imperial College, London, UK, have shown that the application of compression stockings is associated with a significant reduction in pain during the first few days following intervention. In addition, it was found that patients undergoing endothermal ablation and phlebectomies benefited more from compression in the postoperative course.

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he findings of the “Compression following endothermal ablation” (COMETA) investigation were reviewed by Roshan Bootun (Imperial College, London, UK) at the annual meeting of the American Vein and Lymphatic Society (AVLS; 7–10 November 2019, Phoenix, USA). He began: “As we know from interventional treatment, most patients end up with bandaging for a variable period of time, followed by compression stockings, which are often worn for a very long period of time as well.”

Based on National Institute of Health and Care Excellence (NICE) guidelines in the UK, for the treatment of varicose veins in the legs, it is recommended that compression bandaging or hosiery should only be used following interventional treatment for a maximum of seven days. In response to this, the COMETA study was launched, with the aim of testing compression after thermal ablation by establishing pain scores over the first 10 postoperative days.

According to Bootun, patients with reflux of the great saphenous vein (GSV) or small saphenous vein

(SSV) were randomised to one of two groups, receiving compression stockings for seven days or no stockings at all. Stockings used in the study were Class II (18–24mmHg), and all patients wore them for the first 24 hours post-intervention. Furthermore, the multicentre trial was conducted across two sites in London.

Overall, 206 symptomatic patients with venous reflux of more than 0.5 seconds were randomised into either

As we know from interventional treatment, most patients end up with bandaging for a variable period of time, followed by compression stockings.”

Patients treated for pathologic perforator veins should be evaluated for multilevel disease Findings from a recent study on whether a pathologic perforator can predict the presence of an ipsilateral central venous stenosis, as presented at the annual meeting of the American Vein and Lymphatic Society (AVLS; 7–10 November 2019, Phoenix, USA), support the concept of multilevel disease in patients with severe chronic venous insufficiency.

MIKEL SADEK (NYU Langone Health, New York, USA) opened his talk by acknowledging that “there is a spectrum of presentation in chronic venous insufficiency”. However, he added, “the focus here is on the most severe of those presentations, where tissue damage is recurring”.

Sadek explained that there are a number of treatments for both the superficial and deep veins, and, in the case of the latter, the number of options around stenting are increasing. In terms of perforator veins, established guidelines from the American Venous Forum (AVF) and Society for Vascular Surgery (SVS) define the pathologic perforator as any perforator vein that is greater than 3.5mm in diameter with more than 500 milliseconds reflux, including in the presence of active or healed ulceration.

Moreover, Sadek detailed that the practice pattern at NYU Langone Health also included the treatment of patients with C4b venous disease, according to the CEAP classification system. Sadek added: “There are also well delineated guidelines for the treatment of varicose

veins, put forth by both AVF and SVS, as well as other recommendations which form a foundation for appropriate treatment in the event of venous leg ulceration.”

While there is a definition for treatment of a pathologic perforator, little information exists on the treatment of central venous obstruction. With regard to the study conducted by Sadek et al, the hypothesis was that severe disease in the pathologic perforator, “somewhat akin to arterial disease”, may be related to multilevel disease. In order to test this, the study examined whether the presence of a pathologic perforator is predictive of central venous pathology.

The single-centre, retrospective review, conducted by Sadek and colleagues between May 2016 and April 2018, included patients who fit the definition for pathologic perforator veins outlined in both the AVF and SVS guidelines, in addition to patients with C4b disease or worse.

According to Sadek, most of these patients

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the compression cohort (100 patients) or no compression group (104 patients). At the two-week follow up, a pain score from the first 10 days was recorded as a primary outcome, as well as other secondary outcomes such as ecchymosis score, time to resume activities, and the venous clinical severity score (VCSS). There was no significant difference in terms of baseline characteristics and veins treated between the two cohorts.

Bootun underlined that of those randomised to compression, they had follow-up data for 63%, compared to 66% in the non-compression group. “If we look at the pain score using a visual analogue scale (VAS), we found that the results were significantly better in the compression group on days two, three and four,” the presenter revealed, before adding that “a subgroup analysis of patients who underwent interventional treatment with phlebectomy showed that the pain score was much better with compression stockings on days one to three, five and seven”.

Further analysis of the follow-up data showed that there was no significant difference between the groups after two weeks with regard to VCSS, generic quality of life, and disease-specific quality of life. Moreover, the time to return to normal activities between both cohorts was also similar.

The six-month follow-up data demonstrated very little difference in terms of complete occlusion rates (87.5% in the compression group vs. 92% in the noncompression group) and the incidence of deep vein thrombosis (with just one case recorded), while a similar improvement in clinical and quality of life scores was discovered at six months as well. Summarising the findings of COMETA, Bootun concluded that “the effect of compression on endothermal ablation alone is still unclear”.

had not undergone dedicated central venous imaging, “because they were going down one pathway or the other”, and in most cases this was performed incidentally.

Two groups—those who had undergone central imaging, and those who had not—were then compared in terms of two primary outcomes; a reduction in diameter of more than 50%, and a cross-sectional surface area reduction of over 50%. “The total number of perforators which had been treated was 63,” Sadek said, “18 of which had undergone imaging and 45 of which had not.”

As this was not a randomised controlled trial, there were some differences between the two patient populations; the 18 who had undergone imaging had a much a higher history of venous thromboembolism (VTE; 67.6% compared to 6.7%), as well as slightly higher VCSS scores (10.7±5.6, compared to 7.4±4.1). However, CEAP scores were roughly the same between both of the cohorts.

Looking at the imaging group further, Sadek commented: “Only two patients had undergone venography and intravenous ultrasound (IVUS) during the study. They were both found to have significant central venous stenoses and underwent stenting.

With regard to patients with ipsilateral central vein compression, one was excluded because they were found to have Mikel Sadek

a stent that was here before unknown.”

Ultimately, concordant central stenosis was identified in 83.3% of the imaging cohort, with the common iliac vein of two thirds and the external iliac vein of the other third affected. Other axial imaging findings, as summarised by Sadek, included prestenotic dilatation, which was found in 38.9% of the group, and ipsilateral abdominal wall collaterals in 16.7%. “When you look at the actual amount of cross-sectional surface area or diameter reduction, particularly in those patients with stenosis, it exceeded 70% on average,” Sadek added.

Turning his attention to the contralateral limbs in those same patients, the speaker emphasised that compressions were identified in just 44.4% of patients, which represented a statistically significant difference (p=0.0354). One additional patient underwent venous stenting and, along with three other patients who received the combined treatment of the perforator vein with central venous stenting, achieved full ulcer healing within four weeks.

Noting some of the study’s limitations, and looking to the next phase of research, Sadek concluded: “There was only a small sample size and not all of these patients received the gold standard of imaging with venogram and IVUS. Additional longitudinal evaluation is also required to determine if outcomes are affected, in terms of ulcer healing, recurrence and prevention, as well as additional quality of life metrics.”

Nevertheless, the results show that in patients who warrant treatment of a pathologic perforator, “evaluation of the central veins may be indicated”.

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January 2020 | Issue 13

Superficial veins

Lower polidocanol-to-air ratio for reticular vein treatment demonstrates “similar” efficacy and safety In the treatment of reticular veins of the lower extremities using polidocanol foam, it has been found that both a 1:2 ratio and 1:4 ratio of polidocanol to air demonstrate similar levels of efficacy and safety. According to Elika Hoss (Mayo Clinic, Scottsdale, USA), the effectiveness of both ratios was determined by patient and physician evaluation.

“AS YOU KNOW, sclerotherapy is the gold standard treatment for lower extremity reticular veins and telangiectasias,” said Hoss, who was speaking at the annual meeting of the American Vein and Lymphatic Society (AVLS; 7–10 November 2019, Phoenix, USA).

Explaining how this procedure works, Hoss continued: “With the injection of a sclerosant, we have control of inflammation and fibrous cord formation. Also, foam sclerotherapy involves the off-label addition of a gas to the liquid sclerosing agent to create a foam.”

Highlighting some of the advantages of foam sclerotherapy, Hoss underlined that foam displaces blood, allowing for greater contact time with the vessel wall and greater endothelial cell injury. In addition to this, the vasospastic response caused by the foam increases the likelihood of vein closure.

“The effect of different ratios of foam stability and efficacy has been controversial,” commented Hoss, who highlighted that the European consensus recommends a sclerosant to air ratio of 1:4. In order to determine whether a 1:2 ratio would be more efficacious, a prospective, randomised, split-body study of 30 patients (between the age of 25 and 70 years) was established.

Hoss and her colleagues’ study, which was also patient- and evaluator-blinded, included patients with Fitzpatrick skin type I-IV, as well as C1 bilateral and symmetric lower extremity reticular veins

and telangiectasias under the CEAP classification. Alternatively, patients with visible varicosities, skin changes of venous stasis, deep vein incompetence, and a history of deep vein thrombosis (DVT) were excluded.

Outlining the experimental design, Hoss said: “All patients received sclerotherapy to the bilateral legs on two consecutive days. Reticular veins were randomised to treatment with polidocanol 0.5% foam in either a 1:2 or 1:4 ratio, while telangiectasias were treated with glycerin. Elika Hoss

The effect of different ratios of foam stability and efficacy has been controversial.”

In addition, all patients received thigh-high 30–40mmHg graduated compression stockings, which were worn for seven days.”

Investigator evaluations, as part of the study, included a blinded assessment of adverse events (such

as erythema, pigmentation or swelling) postprocedure on day zero and day one. Adverse events were also evaluated at both 21 days and 90 days, in addition to blinded evaluation of improvement that was ranked from 1–4. In terms of subject evaluation, there was a blinded assessment of adverse events (including pain during or after injection) on day zero and one, as well as a blinded evaluation of improvement, again after 21 days and 90 days. Patients were also asked to keep an outcome diary, highlighting adverse events up to week 12.

Safety results from the 30 patients enrolled in the study (all female; mean age of 54 years) showed that there was “no statistically significant difference” in investigator-assessed adverse events at baseline, 21 days or 90 days. Moreover, no statistically significant difference was found in subject-assessed adverse events between groups, including the patient diary which noted similar levels of pain, swelling, bruising and itchiness between groups at any time point.

Looking at the study’s efficacy findings, Hoss stated that a “0–50% improvement was seen at day 21 by investigators, and a 26–75% improvement at day 90; there was no statistically significant difference though between legs”. She added that “subjects found similar rates of improvement (0–50% at day 21; 26–75% at day 90)”, again showing no statistically significant difference.

Concluding her presentation, Hoss closed: “The two different polidocanol to air ratios were similar in efficacy and safety for the treatment of reticular veins of the lower extremities. Limitations of the study include the use a quartile scale for improvement, and one may consider using a 1:4 ratio, given that it allows for a lower concentration of polidocanol to be used. Further studies may be considered for high polidocanol to air ratios.”

Retrospective study demonstrates efficacy of radiofrequency ablation and open surgery for varicose vein treatment Long-term evaluation of superficial venous reflux below the knee, in patients who received invasive treatment for varicose veins, has found that both radiofrequency ablation (RFA) and open surgery achieve “acceptable and comparable results”. The retrospective cohort study was presented at the annual meeting of the American Vein and Lymphatic Society (AVLS; 7–10 November 2019, Phoenix, USA).

“V

aricose veins are a widespread problem,” said Beatrix Cucuruz (Goethe University Hospital, Frankfurt, Germany; Center for Vascular Disease, Nuremberg, Germany), who discussed the findings of the investigation. The speaker underlined that up to 30% of the population have varicose veins which should be treated, and added that “paraesthesia is reported in 4–20% of patients after stripping of the great saphenous vein (GSV)”.

Regarding the treatment options available, Cucuruz explained that “in our institute, we mainly use RFA or open varicose vein surgeries,” though other ablation techniques, such as endovenous laser ablation (EVLA), mechanochemical ablation (MOCA) and chemical ablation, as well as foam sclerotherapy, can be utilised.

The aim of the study was to examine whether or not postoperative paraesthesia can be reduced with RFA, and if there is a durable occlusion of the veins following this procedure. Moreover, the

study sought to determine the incidence of recurrent varicose veins and whether there are any changes of the remaining GSV at the thigh after RFA. “We looked for patients who were treated for varicose veins between January 2007 and December 2008,” said the speaker who, outlining the study methods, commented that “all of these persons presented with incompetence of the GSV down to the ankle”. RFA was conducted using the ClosureFast catheter from Medtronic, and all patients wore compression stocking for six weeks following their treatment.

The data collected showed that 60 patients were treated during this period with RFA, while 352 underwent open surgery. Twenty-four of those 352 patients were treated with stripping of the GSV above the knee, instead of the entire vein. In terms of the demographics analysed in each of the two groups (RFA and open surgery), there was no significant difference in terms of age or previous heart disease. However,

Cucuruz also highlighted that the number of patients in the RFA group who had a history of deep vein thrombosis (DVT) was higher Beatrix Cucuruz compared to the open surgery cohort (12/60 vs. 4/352, p=0.001).

With a technical success rate of 100%, results of the study showed that following RFA, just one patient out of 60 (2%) experienced paraesthesia during the postoperative course. Out of those who underwent open surgery with stripping of the entire GSV, 8% developed postoperative paraesthesia (27 out of 328), while none of the 24 in whom the GSV was stripped only above the knee experienced this.

Turning her attention to the long-term follow-up data, Cucuruz revealed that the recanalisation rate after RFA was 12% (7/60); the recurrence rate was

15% (9/60) following this procedure. By comparison, the recurrence rate following open surgery on the entire GSV was 12% (40/328), higher than the 8.3% recurrence rate (2/24) for patients who underwent stripping above the knee.

“Looking at the follow-up for patients with remaining GSV at the calf (60 patients who had undergone RFA, plus 24 patients who underwent stripping above the knee), 98% (82/84) did not show any reflux,” explained Cucuruz. “Also, only 2 out of 82 (2%) patients show progression of GSV incompetence with indication for reintervention”.

Summarising her findings, Cucuruz concluded: “In almost all patients, reflux of the GSV below the knee was abolished. In addition, there was a higher rate of postoperative paraesthesia in patients with stripping of the entire GSV. The number of patients lost to follow-up was a limitation of the study though, as this was a lot more common in the group who underwent open surgery for varicose veins.”

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January 2020 | Issue 13

Ultrasound imaging

Intravascular ultrasound shows superiority over venography in identifying key parameters for iliac vein stenting Based on the results of a retrospective, single-centre cohort study conducted at The RANE Center, St Dominic’s Memorial Hospital (Jackson, USA), the importance of intravascular ultrasound (IVUS) for identifying the location and severity of stenotic lesions in the iliac vein has been affirmed. Findings of a blinded comparison showed that IVUS is superior to venography as a method of determining treatment zones for iliac vein stenting.

C

ommenting on the research, which was recently published in the Journal of Vascular Surgery: Venous and Lymphatic Disorders, lead author Myriam Montminy (Jackson, USA) said: “Adequate assessment of the location and degree of stenosis, and delineation of venous anatomy for optimal landing zones are key in the success of interventions to treat chronic obstructions of the deep venous system.”

“While venography is more accessible and less expensive to perform than IVUS,” as Montminy explains, “an increasing number of studies demonstrate that IVUS is significantly more sensitive than venography in identifying stenotic lesions in the iliac-caval segments”. Following on from these investigations, the study conducted by Montminy and colleagues at St Dominic’s Memorial Hospital aimed to compare these modalities for identifying the key parameters required to guide stent placement”.

Cases were analysed from the period between October 2013 and November 2015, with 155 limbs (152 patients) counted as having undergone an endovascular intervention for chronic iliofemoral vein

stenosis. Furthermore, both venography and IVUS were conducted in all of the cases utilised as part of the study.

Venography and IVUS data from these cases were reviewed by vascular surgeons and radiologists, who were blinded to each other to identify the location and severity of maximal stenosis, location of iliac-caval confluence, and optimal distal landing zone, before comparison. In addition to this, maximal stenosis was defined as the most severe stenosis found among the common iliac vein, external iliac vein, common femoral vein, and infrarenal vena cava.

Key demographics of the series were also included in the research: patients analysed had a mean age of 59 years, 30% involved male patients, and 61% of limbs treated were the left leg. Also, 72% of the patients included in the study were post-thrombotic.

Results of the study demonstrated a failure of venography to identify lesion existence in 19% of limbs, while the median maximal area stenosis was significantly higher with IVUS than with venography (69% vs. 52%; p<0.0001). It was also found that venographic correlation with IVUS for the anatomic

Duplex ultrasound limited for early diagnosis of subclavian vein thrombosis There are “significant limitations” to the use of duplex ultrasound for the initial evaluation of patients with suspected subclavian vein (SCV) thrombosis, according to the findings of a retrospective, single-centre review published in the Journal of Vascular Surgery: Venous and Lymphatic Disorders. Moreover, the investigators asserted that false-negative ultrasound studies have the potential to delay definitive imaging, thrombolysis, and further treatment for venous thoracic outlet syndrome (VTOS).

CONDUCTED BY Robert Thompson (Washington University School of Medicine, St Louis, USA) et al at the Center for Thoracic Outlet Syndrome and the Section of Vascular Surgery, St Louis, USA, the goal of the review was to “assess both the utilisation and consequences of upper extremity duplex ultrasound in the initial diagnostic evaluation of patients with suspected SCV thrombosis and VTOS”.

A form of primary upper extremity deep vein thrombosis (UE-DVT), SCV thrombosis (or Paget-Schroetter syndrome) is caused by extrinsic compression of the central SCV “at the level of the costoclavicular space”, also known as VTOS. Although duplex ultrasound is acknowledged to be both sensitive and specific in the diagnosis of UE-DVT—and is widely considered to be the standard technique of initial

evaluation for this condition—its accuracy in visualising the subclavian and brachiocephalic veins is limited by the clavicle.

As a result of this, an ultrasound may be unsuited for the early diagnosis of VTOS, “when focal central SCV obstruction has not yet led to distal thrombus extension, and its widespread use raises the likelihood that VTOS will be unrecognised and undertreated”. To address this, Thompson and colleagues’ investigation examined patients who underwent surgical treatment for VTOS between 2008 and 2017.

In addition to undergoing surgical treatment for VTOS, patients included in the review must have received an upper extremity ultrasound as the initial diagnostic test. Patients with neurogenic or arterial forms of VTOS were excluded from the review, as well as persons

location of maximal stenosis was present in only 32% of the limbs. In terms of iliac-caval confluence, location on venography only correlated with IVUS in 15% of patients and, in 74%, was located higher with IVUS than with venography. Finally, correlation between venography and IVUS on location of the distal landing zone was only 26%.

Commenting on these findings, which suggest that IVUS is the better diagnostic and procedural tool in iliac-caval stenting, Montminy stated: “This study highlights that venography, when compared to IVUS, is likely to be deficient in all three areas of concern in venous stenting cases: location of the maximal stenosis as well as the optimal proximal and distal landing zones.” On the other hand, it was confirmed by Montminy that venography remains a valuable adjunct in iliac vein stenting, as it provides a panoramic view of the pathologic process. “Additionally, IVUS may miss or provide only a partial image of certain lesions situated at the hypogastric-iliac and iliac-caval confluences due to the absence of a centring mechanism,” she argued.

Although there is no evidence yet to confirm whether

This study highlights that venography compared to IVUS is likely to be deficient in all three areas of concern in venous stenting cases.” the superiority of IVUS in identifying key parameters for iliac vein stenting would improve outcomes, the cohort study conducted by Montminy et al was able to “further define the complementary roles of venography and IVUS in this growing area of vascular intervention”.

with VTOS undergoing reoperative procedures or operations for threatened haemodialysis access. Once the 214 patients who fit these criteria were identified, the clinical and treatment characteristics of patients with both positive and false-negative ultrasound studies were compared.

Results of the study showed that there were 122 men (57%) and 92 women (43%) who presented with spontaneous idiopathic arm swelling, 28 of whom (13%) had proven pulmonary embolism.

Upper extremity ultrasound had been performed 23.8±12.2 days after the onset of symptoms, and axillary-SCV thrombosis was diagnosed in 169 patients (79%), while 45 (21%) came back with false-negative results. Only eight (18%) of the false-negative study reports acknowledged limitations in visualising the central SCV. Furthermore, “definitive diagnostic imaging (DDI) had been obtained by upper extremity venography in 175 (82%) patients, computed tomography angiography in 24 (11%), and magnetic resonance angiography in 15 (7%), with 142 (66%) undergoing catheter-directed axillary-SCV thrombolysis,” the findings revealed. Between the initial ultrasound and DDI, there was a mean interval of 48.9±14.2 days. Although there was no significant difference between groups in this regard, it was found that patients with a positive ultrasound were more likely to have DDI in 48 hours (44% vs.

24% in the false-negative group; p=0.02).

Other results of the retrospective review showed that patients with falsenegative initial ultrasound studies were significantly more likely to Robert Thompson require SCV bypass reconstruction than those with a positive ultrasound (44% vs. 25%; p=0.02). Also, the SCV was widely patent following paraclavicular decompression and external venolysis alone in 74 patients (35%) at the time of surgical treatment, with patch angioplasty performed for focal SCV stenosis in 76 patients (36%) and bypass graft reconstruction for long-segment axillarySCV occlusion in 63 (29%).

Speaking to Venous News about the results, Thompson concluded: “The results of this study strongly challenge the reliance on venous duplex ultrasound imaging in the initial assessment of subclavian vein ‘effort thrombosis’ and suggest that it may even be detrimental.

“We would recommend that any young healthy person with sudden, whole arm swelling and discolouration should be suspected to have SCV thrombosis due to VTOS, until proven otherwise by a contrast venogram. Venography is a better choice for initial evaluation, as it also allows the prompt undertaking of venous thrombolysis, a valuable step in the management of this condition prior to definitive surgical treatment.”

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January 2020 | Issue 13

Interview

Profile

Raghu Kolluri

Following his recent appointment as president of the Society for Vascular Medicine (SVM), Raghu Kolluri (Columbus, USA) speaks to Venous News about how the venous field is being affected by the results of recent trials, his involvement with The VEINS at VIVA, and key areas of innovation to watch out for in 2020.

When did you decide to enter the field of vascular medicine?

I decided to enter the field of vascular medicine towards the end of my first year of an internal medicine residency at Riverside Methodist Hospital (Columbus, USA). I saw a patient with bilateral brachial artery fibromuscular dysplasia, which I reported along with my mentor (now my colleague and partner at work) Gary Ansel (Columbus, USA). I was fascinated by the field of vascular medicine and was able to do a month of “awayrotation” at The Cleveland Clinic’s Vascular Medicine section during my second year of residency training.

I fell in love with vascular medicine during that time.

Following residency training, I went to The Cleveland Clinic for advanced fellowship training in vascular medicine. We were trained to manage all aspects of vascular disorders and thrombosis, and I was exposed to the first iteration of radiofrequency ablation technology and other superficial venous therapies. Although I enjoy practicing all aspects of vascular medicine, I was particularly attracted to venous disease since it was a highly neglected field at that time. My interest in venous disease only became stronger later on in clinical practice, as I cared for many patients suffering from debilitating venous disease.

During your training, were there any vascular or venous specialists who particularly inspired you?

Of course, I have several role models and mentors. Ansel and Mitchell Silver (Columbus, USA), now my practice partners, encouraged me to get into the field of vascular medicine while in training. Spending time with Ansel on the hospital floors and in the cath lab was truly inspiring.

The one individual who influenced my professional life the most is John Bartholomew (Cleveland, USA).

He trained several doctors in vascular medicine and genuinely cares for his patients. His thoroughness in every aspect of patient care left a significant impact on my career, and his passion for thrombosis and venous disease has rubbed off on me.

How has the venous field changed, and do you agree that future trials must focus on “technical success”?

Venous care is still a relatively neglected field, especially when compared to peripheral arterial disease (PAD) or coronary artery disease (CAD). Nevertheless, we have come a long way, with tremendous growth in the venous space in the last couple of decades. I recall a time when deep venous interventions were offered only for palliative care, and therapies for long-term sequelae of post-thrombotic syndrome were available only in a few select centres in the USA. I hope venous patients will ultimately benefit from evolving technologies in the superficial and deep venous space, and for pulmonary embolism (PE). I agree that we must focus on technical success in deep venous interventional trials, but appropriate assessment of technical success is equally important. Also, patient-reported outcomes are as important as anatomic success; ultimately, the patient needs to feel better.

What are some of the key areas of innovation that currently interest you?

We are a large Health System in Central Ohio, with 14 hospitals and more than 20 vascular laboratories. We are interested in all aspects of innovation that improve our patients’ lives. I am very excited about some of the advances in duplex imaging. Multi-row array technology allows a lot more elements to be packed into the new ultrasound probe, leading to exceptionally high-resolution images. Visualisation of slow flow and deep structures is fascinating. 3D ultrasound imaging and ultrasound contrast may have some future vascular applications. Point-of-care ultrasound is another area of interest, and I believe this will change the way physicians practice and examine patients. I would also like to see increased utilisation of simultaneous extravascular and intravascular ultrasound in cath labs.

We are also interested in thrombectomy devices for PE and deep vein thrombosis (DVT) management that hopefully will reduce bleeding risks and improve outcomes.

I hope venous patients will ultimately benefit from evolving technologies in the superficial and deep venous space, and for pulmonary embolism.”

Before The VEINS, fellow course director John Kaufman described you as “a force of nature”; how successful was the programme this year?

That is very kind of John. He has been a great partner with the management of this highly successful meeting.

We welcomed 400 attendees representing 31 countries, this year. We have a broad range of venous education at The VEINS, and will continue to listen to our attendees and provide patient-centric educational content. Stay tuned for more announcements with regard to The VEINS’ 2020 programme; we have several unique and innovative sessions planned.

You are also part of the American Venous Forum’s Annual Programme Committee; what can attendees look forward to at the AVF meeting in March?

AVF is a highly scientific organisation and I enjoy attending the AVF meeting every year. As always, the latest in basic and clinical science will be featured, in the form of abstracts and presentations. AVF has also formally partnered with C-TRACT to increase the awareness of the trial and the enrolment process. I look forward to hearing an update on this landmark study by Suresh Vedantham (St. Louis, USA).

How excited are you about your appointment as president of the Society for Vascular Medicine?

SVM is my professional home society and it is an honour to lead this society, which consists of incredible

vascular specialists from all training backgrounds.

Although we are not a large organisation, we certainly are mighty. In my opinion, no single specialty can provide comprehensive vascular care. Nationally and internationally, SVM has partnered with like-minded vascular societies at various levels. We routinely participate in writing Appropriateness Use Criteria (AUC) documents and other vascular guidelines. As the USA’s population ages and the prevalence of vascular disease increases, there is going to be a shortage of vascular specialists. We will explore all options to increase training programmes in vascular medicine in the next few years.

If you had to give one piece of advice to new doctors entering the venous specialty, what would you say?

Understand the disease process and the pathophysiology of venous disease. This is more important than focusing on techniques and technologies. It is also important to remember that manifestations of venous disease

Issue 13 | January 2020

Interview

11

Fact File

Qualifications

1997 MBBS/MD, Armed Forces

Medical College, Pune, India 2001 MS, Pennsylvania State University,

University Park, USA 2004–2005 Fellowship in Vascular Medicine, Section of Vascular Medicine, Division of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, USA

Academic Appointments (selected)

2005–2013 Principal investigator, Prairie Educational Research Co-operative, Springfield, USA 2005–2013 Clinical assistant professor, Southern Illinois University School of Medicine, Springfield, USA

Professional Appointments (selected)

result from complex venolymphatic and cardiovascular interactions. Unless you think outside of the vascular box, you will not be able to help all patients. With a laundry list of venous therapies now available, it is quite easy to miss underlying systemic causes that may mimic symptoms consistent with venous disease. It is not uncommon for me to see patients seeking a second opinion, with persistent symptoms even though their deep veins have been stented and their superficial veins ablated. Above all, stay humble and collaborate.

During your time as a venous specialist, are there any cases which stand out?

I saw a 99-year-old lady with an extremely painful atrophy blanche venous ulcer. She was dealing with this severe pain for at least 15 years. She said: “I am going to turn 100 in six weeks. I want to blow out my birthday candles without any pain. I have been to many doctors, and they all told me that I am too old.” We had

a lengthy discussion about the potential complications with superficial venous therapies. However, with thermal ablation of the great saphenous vein (GSV) and careful sub-ulcer sclerotherapy, we were able to heal the ulcer before she reached her birthday. That was very rewarding.

What are some of your hobbies and interests outside the world of medicine?

I like to exercise my right brain as much as possible.

Photography is a serious hobby: I enjoy taking pictures and post-processing and printing them. What initially started as portrait photography of my three sons then blossomed into landscape and cityscape photography.

I love listening to rock n’ roll and heavy metal music; I even used to play guitar, and hope to pick it up again soon. In my spare time, I try to recreate my mother’s South Indian recipes. Travelling with my family is also something I look forward to every few months.

2005–2013 Director, Vascular medicine,

Prairie Vascular Institute,

Springfield, USA 2011–2013 Medical director of

informatics, Illinois Referral

Division, Hospital Sisters

Health System (St John’s

Hospital, Springfield; St

Francis, Litchfield), Illinois, USA 2013–Present Medical director, Vascular laboratories, OhioHealth, Ohio, USA 2013–Present System medical director, Vascular medicine, OhioHealth Heart and Vascular Service, Ohio, USA

Offices (selected)

2009–2011 Chair, Research committee,

American Board of Phlebology 2019–Present President, Society of Vascular Medicine Present Board member, VIVA Physicians Present Annual Scientific Sessions planning committee, American Venous Forum

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January 2020 | Issue 13

Venous ulcers

Multilayer dressing demonstrates benefits for VLU treatment by effective transport of wound exudate A pilot evaluation of a new multilayer wound dressing has confirmed its efficacy for transporting exudate containing toxic matrix metalloproteases (MMPs) away from chronic venous leg ulcers (VLUs).

PRESENTED BY OSCAR ALVAREZ (University Hospital; Rutgers New Jersey Medical School, Newark, USA) at the Symposium on Advanced Wound Care Fall meeting (SAWC Fall 2019; 12–14 October, Las Vegas, USA), the study was selected as one of four winning oral abstract presentations.

Alvarez began: “As you know, there is a hypothesis that chronic wounds have a prolonged, exaggerated inflammatory phase, and even in an uninfected wound, this is likely due to an imbalance of metalloproteases and gelatinases that break down the components of the provisional matrix as the wound tries to heal.”

Although acute wound fluid is considered quite healthy for cells, chronic wound fluid is toxic, largely because of elevated levels of gelatinases such as MMP-2 and MMP-9 which, in cases of venous ulceration, prevent significant healing from taking place. Discussing the objectives of the evaluation, Alvarez

described the aim of this case series as two-fold; firstly, to study the absorptive profile of Mepilex Border Flex, ensuring that it is suitably designed to spread fluid away from the wound, and secondly, to determine how the use of the dressing impacts upon the balance of proteases in VLUs as they heal.

The method of the study required 10 VLU patients to be treated with the multilayer dressing in addition to compression therapy. As Alvarez explained, all patients included in the investigation had adequate arterial circulation—defined as an ankle-brachial index (ABI) of more than 0.75—and showed no signs of infection. In addition, all VLUs treated as part of the study were less than 25cm² in size, and follow-up visits were conducted weekly in order to measure and evaluate the wounds.

In order to carry out the study, wound fluid was obtained at baseline (day zero, prior to initial treatment) and once every week, for four weeks, from both

the wound and the wound dressing.

Additionally, homogenates were analysed using a custom multiplex kit for MMP-9.

Explaining how the dressing is structured, Alvarez outlined: “The dressing has a printed back layer which is waterproof, a retention layer that actually retains a lot of the fluid, and a spreading layer—which is really the unique part of the dressing—as well as a foam layer which rapidly absorbs exudate, and a silicone layer that prevents trauma to the wound upon dressing removal.”

“A lot of people do not realise that when you put an absorptive dressing on a venous ulcer and you subsequently compress the wound,” Alvarez added, “it changes the complete profile of the dressing.” Furthermore, he emphasised that if the size of the wound is more than 60% of the surface area of the pad within the dressing, it will not succeed because the dressing will not absorb enough.

Results of the evaluation demonstrated a 46% decrease in wound fluid MMP9 levels over the course of two weeks (p=0.042), following treatment with Mepilex Border Flex. After four weeks, those levels had been reduced even further, decreasing by 79% (p=0.029).

Alvarez also revealed that significant levels of MMP-9 were detected in the spreading layer and retention layer of the dressing, which was supported by analyses that show MMP-9 had been transported distally up to 4cm away from the wound.

Alvarez concluded: “The mean MMP levels decreased nearly 50% in

LUPA study confirms effectiveness of accelerated leg ulcer pathway in an urban population “Improved healing needs to be the goal, but also reduced recurrence in the long term,” said Stephen Black (Guy’s and St Thomas’ Hospital, London, UK), during his presentation of results from the Leg Ulcer Pathway Audit (LUPA) study at The VEINS, a special programme of the 2019 Vascular Interventional Advances conference (VIVA; 4–7 November, Las Vegas, USA).

S

peaking to those in attendance, Black pointed to the fact that there is an existing problem with leg ulcer care, with referral practices for patients suffering with these wounds considered to be poor.

Furthermore, there is “a general lack of clarity on what treatment is needed”, while the pathways for leg ulcer patients are also poorly understood.

Although the EVRA trial revealed that early intervention significantly improves the rate of healing, questions have been raised by this study. “Ninety-three percent of patients were excluded with the high screen failure rates,” Black reflected, “while the role of deep venous intervention was unclear, as was the treatment for larger ulcers.”

Standard of care in the local area around Guy’s and St Thomas’ Hospital, described by Black as “a communitybased care model”, was evaluated. He commented that there were multiple different models in place and “very little consistency”. A random selection of 100 patients was monitored, and of these patients just 21% healed.

Alternatively, 76% had not healed or experienced recurrence.

In response to these findings, the LUPA study was established to compare patient outcomes with an accelerated ulcer care pathway to standard of care only.

Black further explained the study rationale: “As part of the LUPA study, we looked at a cohort of consecutive patients [all comers] who underwent the accelerated ulcer care pathway. We also looked at the epidemiology of patients’ ulcers to see what components of deep, superficial and arterial disease there were, as well as barriers to implementation. This is what we would compare to the standard of care pathway already mentioned.”

Of the 130 patients enrolled, 110 were followed up out to 12 months; 15 were lost to follow-up, while five were excluded from evaluation due to disease or other illnesses that were not viewed to be valid comparators.

Black outlined that 75 of the 110 patients were male (68%), and there was an average age in the cohort of 59

We...want to further analyse and understand the healing signals in these [leg ulcer] patients as well.”

Oscar Alvarez

The mean MMP levels decreased nearly 50% in two weeks, and this was statistically significant.” two weeks, and this was statistically significant. Mepilex Border Flex also draws the chronic wound exudate outwards and, for use with VLU compression, optimal absorption depends on the capacity of the dressing and therefore size selection.”

years. Moreover, 53 of the patients (48%) had an ulcer that was more than 12 months old.

Black also noted that a majority of the patients (54%) had a history of deep vein thrombosis, which in some cases of some patients occurred a long time before ulceration. Drawing comparison to trials focusing on the prevention of post-thrombotic syndrome (PTS), he explained: “Ulcers and severe PTS can take a long time to develop, and if we are not following up for long enough, we may be missing this potential differentiator for the treatment of patients.”

Those enrolled in the study underwent a range of different treatment strategies, including superficial venous insufficiency (SVI) treatment (61% of patients) and venous stenting (33%). “This probably correlates well with rate of previous DVT among the patients,” argued Black, “suggesting that iliac outflow obstruction may play a role in these big, long-standing ulcers that have been there for more than 12 months”.

In the accelerated pathway after 12 months, 80% of the ulcers that were treated had healed, with a further 11% of patients on their way to healing. Nine percent of patients had not healed, though Black emphasised that this was not surprising as the type of wounds looked at in the study were large and complex ulcers.

Looking ahead to the next steps of this investigation, Black concluded: “I have one hospital in central London, which means the data and the demographics studied may not be representative of the whole country.

In order to validate these results, we have gone to Oxford and Cambridge to look at a mixture of urban and rural populations, ensuring that this trend stacks up.

“We, of course, want to further analyse and understand the healing signals in some of these patients as well, because what was obvious for us was that we need to identify who is going to benefit from deep venous intervention versus superficial, and what adjunctive treatments are necessary.”

Issue 13 | January 2020

Amniotic membrane wound grafts demonstrate improved healing rates for non-healing venous leg ulcers It has been found that the application of dehydrated human amnion and chorion allografts (dHACA) results in a better venous leg ulcer (VLU) healing rate than the use of standard multilayer compression therapy, following a randomised controlled study comparing the two treatment regimens. Displayed in a poster presentation at the Symposium on Advanced Wound Care Fall meeting (SAWC Fall 2019; 12–14 October, Las Vegas, USA), the trial responds to the “significant clinical, humanistic and economic burden” created

by VLUs.

A

ccording to the research, conducted by principal investigator Thomas Serena (Cambridge, Massachusetts, USA) and colleagues, “millions of Americans are afflicted with painful, open, draining sores on their lower extremities”, many of which have a venous aetiology and are incredibly difficult to heal. Although some patients require weeks or months to recover, a significant number of those suffering with VLUs can take years to heal and may, in some cases, even face amputation as a consequence of their wounds.

In terms of costs, the poster presentation highlighted that “the consequence of long-term disability has been estimated at 4.6 million work days lost per year and a cost to the healthcare system of up to US$2.5 million annually in the USA”. Moreover, current VLU rates are reportedly as low as 30% at 24 weeks, emphasising the need for new, advanced therapies that can achieve better results.

Recent clinical data have shown that dHACA, which feature endogenous growth factors to facilitate wound healing, are more effective than other bioengineered skin substitutes in the treatment of diabetic wounds, prompting a new prospective, multicentre trial to “compare the proportion of ulcers healed completely with the use of dHACA vs. standard of care patients with venous leg ulcers”.

Conducted in eight outpatient wound centres, this was the first study to evaluate the efficacy of dHACA in VLU treatment using weekly and biweekly application regimens against multilayer compression bandaging.

As part of the trial, patients with non-healing VLUs treated with standard of care—consisting of appropriate debridement, a primary absorptive dressing and multilayer compression— after a two-week screening period were randomised to either a standard of care group (20 patients), or a cohort receiving “wound-size specific” dHACA plus multilayer compression applied weekly (20 patients) for up to 12 weeks.The primary endpoint of this trial was the percentage of patients healed at 12 weeks (defined as complete epithelialisation).

At the conclusion of the study, it was discovered that both weekly and

Venous ulcers biweekly application of dHACA resulted in a statistically significant improvement in healing rates for VLUs, when compared to standard wound therapy.

For those patients who received standard of care only, 30% (six out of 20 patients) healed in 12 weeks, with a mean percentage wound area reduction of 57.8%. Alternatively, 75% of patients (15 out of 20) who were treated with dHACA weekly and biweekly healed within 12 weeks, with a mean percentage wound area reduction of 80.7% (p=0.012).

The findings of this study underline that the use of dHACA results in a greater percentage of patients healed within 12 weeks than multilayer

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compression therapy, improving the healing trajectories of patients and benefitting those who had previously failed to heal sufficiently under standard of care.

Speaking to Venous News about the investigation, Serena commented: “The dedicated investigators and research coordinators in the SerenaGroup Research Foundation make publications such as this possible.

“Our cooperative group of clinical research sites conducts roughly a dozen clinical trials per year, publishing 12–15 manuscripts. We are advancing the science of wound healing. We welcome interested physicians and research sites to join the effort.”

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January 2020 | Issue 13

Venous ulcers

Addressing the silent crisis of venous leg ulcers and its impact on patients With the level of spending on wound care in the billions of pounds, both the financial and health-related impact of venous leg ulcers cannot be understated. Dan Carradice (Hull York Medical School, Hull, UK) speaks to Venous News about the latest report by the All-Party Parliamentary Group on Vascular and Venous Disease, which articulates the extent of this important issue, and what can be done to improve care in the UK.

How did the report, “Venous Leg Ulcers: A Silent Crisis”, come about, and why are venous ulcers an important issue?

The thing to say first is that vascular disease is an unwitting victim of the widespread misunderstanding and misdirection of healthcare attention, and I think that this is true all the way from strategy and planning, down to individual patient care. It is clear that vascular disease is the most common cause of death in UK adults, the most common cause of limb loss, and results in a significant level of physical, mental and psychological morbidity across the country. Despite this, it has received precious little attention compared to other diseases, such as cancer, and when it is considered it is usually fragmented, with all attention limited to heart disease and stroke.

The predominant interest of those involved in the management of vascular disease is targeted towards arterial disease, and it is against this backdrop Dan Carradice that venous disease sits in near silence.

I think that this report came about because both patients and their carers are clamouring to be heard, while healthcare professionals are battling to improve care quality and outcomes. For this reason, we have been working with organisations such as Legs Matter, Lindsay Leg Club, and now members of parliament in the group to produce this report, raising awareness of such an important condition.

In terms of the second part of the question, I think that this is an important issue because lower limb venous reflux is one of the most common causes of disease in adults, with a prevalence of about 40–50% in adults overall. It is difficult to know how many people have active venous leg ulcers, as they are frequently misdiagnosed, but at least 200,000 people seek help for these ulcers annually. There are another 420,000 leg wounds treated every year which never receive a formal diagnosis, and we also have some detailed epidemiological studies which estimate a prevalence of around 0.7%, which would equate to around 400,000 active ulcers in the UK.

What are some of the key reasons for the development of venous leg ulcers, and how do these wounds impact patients’ lives?

Venous leg ulcers are caused by high pressure in the veins (venous hypertension), which initiates an inflammatory condition within the skin and the soft tissues of the leg. This results in the breakdown of the skin. There are a range of causes for this increase in venous pressure, but the most important and common, by far, is reflux in the superficial veins of the legs. This, in turn, is also caused by an inflammatory condition in the vein walls, which results in a loss of valvular function.

Ulcers have a profound impact on patients’ lives; they can be painful, distressing and have been shown to significantly limit health-related quality of life, due to physical limitation, social isolation and psychological strain. One study I was involved with performed a

detailed evaluation of objective health-related quality of life, which found that venous ulcers have a similar impact on patients as that of end-stage heart failure.

Is there enough awareness of the physical, social and psychological problems patients with venous leg ulcers experience?

Sadly, I think we are far from where we need to be.

We know this from our own experience as clinicians, but the parliamentary group has also received testimony from multiple people who have been through this condition and suffered from a lack of awareness.

Patients themselves do not understand the significance of their first ulcer when it does occur, as the underlying venous health issues and their implications are not well known. Usually, they will go to see their GP and, if the GP does not know what the wound is, then the patient will try some antibiotics and perhaps try to dress it with a simple adhesive dressing or dermatological creams. In some cases, these patients spend years having such a dressing placed on the wound by a GP practice nurse and never receive access to a vascular specialist. In fact, 75% of patients with known ulcers never receive an appropriate assessment.

For those who are lucky to be diagnosed with a venous leg ulcer, it is still rare that they make the transition from primary to secondary care. Primary care usually involves the conservative management of wounds with dressings, and the quality of these dressings is often quite poor. When they are referred to hospital, some of the commissioning policies can make it challenging to treat them expeditiously, while the lack of investment in this area means that services fail to develop to the level required.

Venous ulcers have a similar impact on patients [in terms of quality of life] as that of end-stage heart failure.”

As part of the report, you wrote about geographical variation in the provision of venous treatments. Could you explain how this “postcode lottery” affects patients?

Geographical variation results in significant inequality of access to NHS services and a failure to deliver clinicallyand cost-effective treatment recommended by the UK’s National Institute for Health and Care Excellence (NICE). This not only leads to poor healthcare, but also inefficient and inequitable use of NHS funding. Both the Government and NHS England are committed to reducing the level of inequality, and, as such, we need to focus on areas like this where inequality is prevalent.

We performed a study where we assessed the published policies of clinical commissioning groups (CCGs) across England, with regard to whether they allowed or prevented the application of NICE’s evidence-based guidelines for the treatment of this venous reflux. Only a third of CCGs had a policy which did not actively prevent the application of these guidelines and evidence-based treatment, while the others employed a range of restrictive or rationing mechanisms, leading to a wide variation in access to treatment. In total, over 90% of patients presenting with superficial reflux do not receive the recommended, evidence-based treatment.

Geographical variation results in significant inequality of access to NHS services.”

What are the key findings of the report with regard to the current state of venous leg ulcer care in the UK?

I think we have found that there is a widespread lack of effective information and knowledge at multiple levels; the patients themselves, among communitybased healthcare professionals and, to a degree, at the level of secondary care. What we have also found is that there is a lack of awareness among commissioners, which has led to a drop in investment for treatment of these conditions and, in turn, a lack of infrastructure in secondary care to be able to deal with them. The All-Party Parliamentary Group actually did a piece of research focusing on the proportion of trusts who had a specific team for delivering this care, and they discovered that only half of the trusts they contacted had a team in place. In addition, significant elements of variation in access and the quality of treatment were found.

Looking ahead, what recommendations do you and your peers offer in the report to improve the quality of venous treatment for patients?

To sum up the most important points from the report, I think that education is a hugely important aspect and this needs to be integral, at both a policy-making level and the community level, as well as at a commissioner and secondary-care level. Moreover, there needs to be a separate arm for patients because they need to know that the longer it takes for these wounds to heal, the harder the task becomes. We have to make sure these patients realise that, by delaying care, they are reducing the ability of healthcare professionals to address this problem, so education is crucial.

The second key element relates to healthcare services; we need to have streamlined and agreed pathways for getting patients from the community into expert assessment, secondary care and, ultimately, expedited treatment. The only way we can do this is by ensuring that we have effective organisation and commissioning in this area of wound care, along with a strong emphasis on education.

We have a solid evidence base upon which we can dramatically improve the outcomes for these patients and enable health services to make considerable financial savings, even in the short-term. We simply need to overcome these practical hurdles and apply our knowledge and skills to transform care in this common and debilitating disease.

Dan Carradice is an academic vascular and endovascular surgeon at Hull York Medical School and Hull University Teaching Hospitals NHS Trust (Hull, UK). He is the clinical lead for vascular surgical services and is actively involved in leading research aiming to improve quality of life, and save life and limb.

Issue 13 | January 2020

Sclerotherapy

An overview of tumescentenhanced sclerotherapy as a treatment for superficial veins Gregory Spitz Comment & Analysis While the treatment of spider, reticular and varicose veins using sclerotherapy has been a standard practice for many years, tumescent-enhanced sclerotherapy has been developed as an office-based technique that takes traditional sclerotherapy a step further by applying a tumescent anaesthetic solution with a peristaltic pump designed for the procedure. Inventor of the technique, Gregory Spitz (Aurora, Illinois, USA), explains in this article how the method was developed and the benefits it can offer.

I

n short, tumescent-enhanced sclerotherapy (TES) provides immediate compression around the vein, thereby helping to maintain the sclerosing agent in the portion of the vein in which it was injected. In addition, the tumescent solution theoretically reduces the inflammation of surrounding tissues—caused by the sclerosing agent—by diluting any of the sclerosing solution that may inadvertently leak out of the vein.

Under pressure, the tumescent solution potentially increases the surface area that the injected sclerosant will be in contact with by displacing blood in the target vessel. Due to the immediate increased compression, the patient may require less post-procedure compression. Moreover, evaluation has shown that this procedure has a short learning curve for the physician, and offers superior ablation of affected veins with fewer treatments.

Patient selection and preparation

Since 2006, TES has been employed in our clinic for the treatment of spider, reticular and varicose veins. When determining the feasibility of using TES as a primary mode of treatment, patient selection and evaluation are incredibly important.

This means that an appropriate background check on the patient’s medical history and physical examination should be performed; this is because patients taking aspirin, antiplatelet drugs or antithrombotic agents need to be treated appropriately, as with standard sclerotherapy.

Those patients selected for the TES procedure are placed in a supine or prone position on the examination table, and it should be noted that a motorised table is a very advantageous tool for this procedure. Standard skin preparation is conducted as part of the process, while the positioning of the leg is determined by the location of the veins to be treated.

Explaining the technique

First and foremost, the office-based procedure does not require the patient to be anaesthetised or sedated prior to TES. The patient’s legs are first marked with an indelible ink marker; spider veins usually do not need to be outlined, while varicose or reticular veins are marked by a simple outline. Very simple equipment is required for the procedure, and we use the sclerotherapy solution polidoconol, ranging from 0.25–1%, and ICC syringes with half-inch 30- and 32-gauge needles.

However, practitioners can use the

Due to the immediate increased compression, the patient may require less post procedure compression.” needles and solution that they normally use for sclerotherapy.

In addition, we utilise a kit that includes a 31-gauge half-inch needle, two 25-gauge 1.5inch needles, gauze pads and sterile tubing for the portable peristaltic infiltration pump. The tubing is unique in that it splits into a Y configuration, allowing two different needles to be used for the tumescent infiltration to be more efficient. In addition, two additional needles, 18- and 20-gauge, are included if drainage of previously treated sites is required.

With the patient prone or supine (depending on the location of the treated veins), sclerotherapy with the 31- and 32-gauge needles commences. The choice of solution for the surgeon is usually based on personal preference, although a more concentrated solution can be used on larger vessels. We utilise two different colour needle hubs to avoid

confusion as to which solution is in which syringe, as well as treating larger veins (any that will have a flashback of blood) with the more concentrated solution 0.596–1%. Alternatively, all others are treated with the smaller 32-gauge needles and syringes, loaded with a less concentrated solution (0.25%).

Furthermore, we tend to approach an area as a cluster or grouping of veins to be treated. After an area is sclerosed, the next step is tumescent infiltration.

For this, a standard tumescent solution consisting of 250ml of 0.9 normal saline, mixed with 10ml of 2% plain lidocaine, 0.25mg of 1:1000 epinephrine and 2.5mEq of sodium bicarbonate, is used.

Our peristaltic pump has a convenient foot pedal that instils the solution from the 25-gauge needles (two of them) attached to the Y tubing. When the foot pedal is depressed the pump activates and when foot pressure is released the pump stops, which allows maximum control of the infiltration. Also, there is a manual clamp on each arm of the Y infusion tubing, so that one or two needles can be used at the same time.

We start with a wheal with one needle and then use both needles to tumesce the treated areas. Then, we bend the 25-gauge needles by 90 degrees prior to infiltration, which enables us to have better control. The endpoint of tumescent infiltration is a “peau d’ orange” (orange peel) effect, and infiltration is complete when a field of 1–2cm forms, in a field block fashion, around the area where sclerotherapy was performed.

The first thing we noticed, in terms of the effects of the TES procedure, was a decrease in post-inflammatory hyperpigmentation, which has been the plague of sclerotherapy since its inception. Further to this, as the treating physician gets more adept at the technique, the instillation of tumescent solution around the area of sclerotherapy occurs almost simultaneously.

Advantages of the procedure

In terms of benefits, especially for patients, there are several advantages to the TES approach to sclerotherapy.

Firstly, this procedure allows for immediate sustained compression, while the sclerosant used can also be isolated in the intended vein. TES also facilitates the dilution of any extravasated sclerosant, as well the separation of skin from the treated vein—this allows for a less inflammatory effect to be had on the skin.

Other benefits of the procedure include the fact that it is well tolerated by patients, a crucial factor. For physicians, it is easy to learn and offers reproducible results, delivering advantages in terms of both time- and cost-efficiency. Finally, the use of TES achieves the desired effect with the use of less concentrated solutions which, in turn, could reduce the number of complications associated with sclerotherapy.

Growing the profile of TES

Following the inception of the procedure, hundreds of surgeons have been trained in this technique, while other tumescentassisted procedures have subsequently

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been developed. Kurosh Parsi (University of New South Wales, Sydney, Australia) is one of several enthusiasts who has also used the procedure, along with Paul Thibault (Broadmeadow, Australia) and Attilio Cavezzi (San Benedetto del Tronto, Italy).

Speaking about the TES procedure, Parsi has said: “It is time we all acknowledge that there is a strong body of science behind the procedure of sclerotherapy and the days of treating sclerotherapy as a simple ‘injection treatment’ are well and truly over. It has been conclusively demonstrated that blood deactivates the sclerosants.

TES ensures an empty vein is obtained at the time of treatment, preventing deactivation by blood and providing internal compression.

“This is particularly important, given the findings of Partsch, Mosti and Uhl that compression stockings do not compress the superficial veins.

By providing internal compression, TES minimises our dependence on external compression provided by compression stockings. The empty vein

For physicians, it is easy to learn and offers reproducible results, delivering advantages in terms of...time- and cost-efficiency.” state ensures exposure of the sclerosant to the target endothelium limiting unwanted interference by blood cells.

In my opinion, the intravascular blood is the ultimate enemy when performing sclerotherapy and should be eliminated at all costs. The TES procedure pioneered by Gregory Spitz and taken up by hundreds of phlebologists is an excellent method to achieve an empty vein state and ultimately good treatment outcomes. Classical complications such as pigmentation and matting can be significantly minimised using this technique. I recommend to all phlebologists to include this procedure in their armamentarium of venous interventions.”

In summary, the TES procedure provides us with a simple, cost-effective way of performing potentially more effective sclerotherapy with a short learning curve, no known significant complications and good cosmetic results in potentially fewer treatments. This can be beneficial for both patients and physicians, and will continue to grow in popularity around the world.

Gregory Spitz is a board certified general surgeon who has been treating vein disease for over 25 years. He has patented several medical devices, including the TriVex System and the Tumescent Inversion Catheter.

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January 2020 | Issue 13

Pulmonary embolism

First pulmonary embolism patient treated with “cyclical” aspiration system Insera Therapeutics’ CLEAR aspiration system has been used for the first time to treat a human patient with acute pulmonary embolism (PE). CLEAR, “cyclical luminal, evaluation, aspiration, and retrieval”, is a digital vacuum aspiration system that allows operators to employ uniform suction or cyclical suction patterns.

ACCORDING TO a press release, the “first-in-human success” of treating PE with CLEAR “comes on the heels” of the recently presented EXTRACT-PE trial. Revealed at the 2019 Vascular Interventional Advances (VIVA) meeting (4–7 November, Las Vegas, USA), the trial evaluated the safety and efficacy of Penumbra’s Indigo aspiration system.

In the study (119 patients), the system was associated with a significant mean reduction in RV:LV of 0.43, corresponding to a 27.3% reduction, at 48 hours after intervention. The primary safety endpoint was reached with a low major adverse event composite rate of 1.7% within 48 hours.

The press release from Insera confirms that the trial—despite focusing on a system from a different company—“advances treatment options for the industry as it establishes the use of vacuum aspiration in patients with acute PE”.

On the use of CLEAR, Luka Novosel (Sisters of Charity Hospital, Zagreb, Croatia) comments: “Due to the large clot burden in the lung arteries, the 65-year-old gentleman presented with right-sided heart failure and was in critical condition.

Traditional treatments using blood thinning medications such as anticoagulation and thrombolytic medications were contraindicated in this patient. We successfully treated this patient with massive

CLEAR aspiration system

bilateral acute pulmonary embolism using Insera’s CLEAR aspiration system. I am very pleased with the ease of use of cyclical aspiration and its ability to rapidly ingest large amounts of clot. It also provides a safer mechanical means of removing life-threatening blood clots without the bleeding risk associated with blood thinning medications.”

The CLEAR aspiration system has European regulatory approval for the aspiration of blood clots, and is indicated for use for acute ischaemic stroke secondary to large vessel occlusive disease. It also has

BIBA Briefings

CE mark approval for aspiration of blood clots from arteries (e.g. PAD, PE, and coronary artery disease) and for the aspiration of blood clots from veins (in patients with deep venous thrombosis, cerebral venous sinus thrombosis or patients with renal failure who have clotted haemodialysis grafts).

Vikram Janardhan, CEO of Insera, comments: “There is a huge unmet need for innovative devices for the removal of life-threatening blood clots. Our cyclical aspiration technology has been shown to improve first-pass recanalisation, reduce distal embolisation, and has an improved safety profile at the time of the procedure. In the USA, it is estimated that every year there are around 225,000 patients with ischaemic strokes due to large vessel occlusions, 300,000 patients with PE, 600,000 patients with deep vein thrombosis, and 100 patients with acute limb ischaemia.”

BIBA Briefings is an online platform (www.bibamedtech.com/bibabriefings) that gives an in-depth analysis of the latest market intelligence from BIBA MedTech Insights (www.bibamedtech.com). It also reviews the latest industry news and pipeline developments.

For editorial enquiries, please contact Dawn Powell: dawn@bibamedical.com For sales enquiries (including BIBA MedTech Insights), please contact Merveille Anderson: merveille@bibamedical.com

Issue 13 | January 2020

Market watch

Product News Hoffman, Inari’s CEO. “We remain committed to revolutionising VTE treatment with devices that remove large clot volume from large vessels while completely eliminating lytics and their consequent cost, ICU stay, and bleeding complications.”

Pilot study confirms beneficial impact of SkinTE on closing venous ulcers

Clinical data on the ClotTriever system demonstrates efficacy for DVT treatment

Inari Medical has announced the presentation of early outcomes from the ClotTriever Outcomes Registry (CLOUT) using the ClotTriever Mechanical Thrombectomy System for treatment of acute and chronic lower extremity deep vein thrombosis (DVT).

Initial results for the first 50 patients were presented by principal investigator David J Dexter, a vascular surgeon at Sentara Healthcare in Norfolk, Virginia, USA, at a latebreaking clinical trials session held at 2019 Vascular Interventional Advances conference (VIVA; 4–7 November, Las Vegas, USA).

CLOUT is a 500-patient prospective, multicentre, single-arm registry evaluating real world patient outcomes after treatment of lower extremity DVT with ClotTriever. According to a press release from Inari Medical, the study is unique in that there are no exclusions for age of clot. Three-quarters of patients had clots over two weeks old and over half failed other therapies prior to treatment.

Nonetheless, thrombus was removed in all patients, and over three-quarters met the study primary effectiveness endpoint of near-complete clot resolution. No patients received thrombolytic drugs, no bleeding complications were reported, and no procedure or device related major adverse events were reported. Average blood loss was less than 30cc.

“Early results from the first 50 patients enrolled in CLOUT are encouraging with 76% of patients free from post-thrombotic syndrome (PTS) within 30 days of treatment,” said Dexter. “We may finally have the tools to truly test the hypothesis that early resolution of venous thrombus in DVT patients may prevent PTS.” “CLOUT reflects Inari’s long-term commitment to the care of venous thromboembolism (VTE) patients, and to the production of clinical data to further the understanding and advance the treatment of this disease,” said Bill

PolarityTE has announced findings from an open-label, single-arm pilot study, which examined the impact of SkinTE in closing venous stasis leg ulcers (VLUs) following the failure of conventional treatments.

The clinical outcomes were reported in a poster presentation, entitled “Pilot study assessing novel autologous homologous skin construct treatment of venous stasis leg ulcers”, at the Symposium on Advanced Wound Care Fall meeting (SAWC Fall 2019; 12–14 October, Las Vegas, USA).

“The completion of this pilot study is a pivotal step in further establishing SkinTE as a treatment for VLUs,” said study first author David Armstrong (Keck School of Medicine, University of Southern California, Los Angeles, USA). He added: “As a clinician and researcher, study findings provide valuable learnings into real-world outcomes and offer the opportunity to broaden treatment options for healthcare providers and patients. We look forward to further data that build upon these initial results.”

The pilot study included 10 patients with VLUs that remained open after at least one month of conventional treatments. The patients were treated with SkinTE, an autologous, homologous human cellular and tissuebased product designed to regenerate full-thickness, functional skin for the repair, reconstruction, and replacement of a patient’s own skin.

The study found an 80% closure rate of the VLUs within 12 weeks after treatment with SkinTE. In addition, all of the patients’ wounds demonstrated graft take and initial signs of closure, including granulation and progressive epithelialisation, shortly after a single treatment with SkinTE. One VLU, which had previously been deemed closed, had reopened prior to the two-week durability visit as a result of external factors unrelated to the SkinTE procedure. Furthermore, another VLU did not close within 12 weeks, which was the largest in the study (12.2cm2) and had remained open for several months prior to treatment with SkinTE after previously failed treatment with a split-thickness skin graft; this VLU closed within 13.5 weeks post application of SkinTE. “We are pleased with the results of our VLU pilot study and today’s announcement further signifies the

strides we are making to build a comprehensive clinical body of evidence to validate the utility of SkinTE,” said Nikolai Sopko, chief scientific officer of PolarityTE. “As we look ahead, we remain committed to investing in clinical initiatives that meet the needs of patients, healthcare providers, and payers. Importantly, the goal of our VLU pilot study was to gain critical insights to design our multicentre, randomised controlled trial, which is currently enrolling patients and will rigorously evaluate the ability of SkinTE to treat VLUs in a larger subset of patients.”

FDA approval granted to calf stimulation device for patients at high VTE risk

UK-based Sky Medical Technology has received US Food and Drug Administration (FDA) 510(k) clearance for its geko device for stimulation of the calf muscles to prevent venous thrombosis in non-surgical patients at risk for venous thromboembolism (VTE).

This adds to Sky’s established 510(k) clearance for immediate post-surgical stimulation of calf muscles to prevent VTE, increasing blood circulation and oedema reduction. According to a statement, this is the first muscle pump activator of its kind to be cleared by the FDA for VTE prevention across all patients including non-surgical patients.

VTE is a deadly risk to hospitalised patients, particularly those who are immobile as a result of recovery, and fewer than 50% of hospital patients receive appropriate preventive treatment according to the CDC (Centers for Disease Control). Estimates suggest that somewhere between 60,000 and 100,000 Americans die each year as a result of the condition, with 10–30% of patients

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the geko device alone, compared to VTEs in the various control groups who were prescribed sequential compression devices (SCDs) at 2.4% or pharmacological prophylaxis at 1.1%.

The investigators, led by Indira Natarajan (NHS Royal Stoke University Hospital, Stoke-on-Trent, UK), also determined that 30% of patients are contraindicated or became intolerant to SCDs. It is to this unmet need cohort that the geko device was fitted, reporting a VTE incidence of zero and good patient tolerance. The data is said to have driven rapid adoption across multiple NHS trusts and international markets, as well as gaining expanded FDA clearance.

Commenting on the study result, Natarajan said: “The data has shown a need to use the geko device when other VTE prophylaxis strategies are contraindicated or impractical, and provides an option where previously patients would have had no other intervention available to them. The geko device is now in routine use at the Royal Stoke and has marked significant change to our practice.”

Embracing the innovation, Fred Rincon (Thomas Jefferson University, Philadelphia, USA) added: “The geko device represents an exciting new treatment option for clinicians to manage stroke patients at risk for developing a deep vein thrombosis when clinicians are concerned about bleeding in the early management of the patient.”

Commenting on the FDA clearance, Sky CEO Bernard Ross also commented: “This latest 510(k) builds on our previous FDA indications to address life-threatening blood clots and complications related to swelling after orthopaedic surgery, conditions experienced by more than one million US patients with unmet need every year.

geko with OnPulse technology

dying within one month of diagnosis.

The geko device is a non-invasive, easy to use, battery-powered, and wearable therapy device which, worn at the knee, gently stimulates the common peroneal nerve, activating the calf and foot muscle pumps and resulting in increased blood flow in the deep veins of the calf. Further, the geko device also operates without external pressure to the leg and allows complete mobility.

A study of the geko device’s ability to prevent VTE in acute stroke patients reported 0% VTEs in patients wearing

We are excited to extend our access into the US market.

“Our muscle pump activation technology, OnPulse, embedded in the geko device, completely redefines the way vascular related conditions are treated. Through our innovative mechanism of neuromuscular electrostimulation, we are the first clinically proven muscle activation technology to prevent and treat a wide range of acute and chronic circulatory conditions both here in the US and internationally.”

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January 2020 | Issue 13

Market watch

Industry News C-TRACT trial on imageguided procedures for mitigating post-thrombotic syndrome partners with AVF

Writing to members of the American Venous Forum (AVF), president Brajesh K Lal (Baltimore, USA), has revealed that the AVF has established a partnership with the C-TRACT study, a randomised controlled trial funded by the National Institutes of Health. As part of the collaboration, AVF will contribute its expertise, perspective, and work effort to advance the trial’s success.

In his letter, Lal described the C-TRACT trial as a large study of endovascular therapy for postthrombotic syndrome (PTS).

Furthermore, the aim of the study is to understand whether image-guided procedures reduce the severity of PTS and improve patients’ quality of life. While long-term safety and costs of endovascular procedures are also being evaluated, the findings of the trial will provide new information on optimal ways to care for patients with PTS. Twenty-three clinical centres are currently participating in C-TRACT,

with availability for more to join.

The partnership expands AVF’s tradition of leadership in promoting evidence-based practice in venous and lymphatic disease. As part of agreement with C-TRACT, which is led by Suresh Vedantham (St Louis, USA), AVF will leverage its knowledge and resources to increase awareness of the study, as well as helping to identify investigators and sites to participate in the study, encourage enrolment, and promote best practices for study conduct.

Discussions of C-TRACT will be presented at AVF meetings, including the 32nd annual meeting of AVF (March 3–6 2020, Amelia Island, Florida) and the Fall and Spring AVF Fellows’ courses. It will also be discussed during AVF sessions at other society meetings and in AVF’s scientific journal, Journal of Vascular Surgery: Venous and Lymphatic Disorders.

Speaking to Venous News, chief investigator of the C-TRACT trial Vedantham said: “We are grateful to the AVF for its strong support of the C-TRACT trial. The AVF has a distinguished history of advancing

venous research, so this is a perfect fit. This partnership will promote the study’s success and provide insights into a new community partnership model that can benefit future studies.

“The investment of $12 million in this study by the NIH demonstrates its awareness of the potential for endovascular stent therapy to reduce disability in patients with postthrombotic syndrome. As such, the C-TRACT investigators and the AVF have a golden opportunity to develop high-quality evidence that secures access to innovative therapy for patients suffering with this condition.”

Robert B Ford to take over as CEO of Abbott

Miles D White will be stepping down, after 21 years, as CEO of Abbott on 31 March 2020. White’s tenure, according to a press release, is the second longest for a non-founder in today’s S&P 100; he will remain executive chairman of the Board. The Board has unanimously appointed Robert B Ford—a 23-year Abbott veteran—to succeed White. Ford currently serves as president and chief operating officer and has been elected to the Board.

Ford will become the 13th CEO of Abbott in its 131-year history; all CEOs having been appointed from within the company, which the press release

calls “a testament to Abbott’s strong management philosophy and successionplanning discipline”. Ford originally joined Abbott in the Company’s Diabetes Care business in 1996. He was appointed president and chief operating officer in October 2018.

According to the press release, Ford has served in many leadership roles within the company, including in the Nutrition and Medical Device businesses. As executive vice president of Medical Devices, he oversaw the integration of St Jude Medical, Abbott’s largest acquisition, and led Abbott’s Diabetes Care business and the launch of FreeStyle Libre.

“It is a tremendous honour to have the opportunity to lead Abbott. I thank Miles for his mentorship, and I look forward to working with my colleagues to do what Abbott people do best— anticipate where science, medicine and technology are going and innovate to best serve our customers, shareholders and communities,” Ford comments.

White was named chairman and CEO in 1998. He has strategically re-shaped Abbott several times, most recently building Abbott’s leadership in medical devices and diagnostics with the additions of St Jude Medical and Alere, and internal advances like FreeStyle Libre, and the Alinity family of diagnostics systems.

Calendar of events 23–25 January CACVS: Controversies and Updates in Vascular Surgery Paris, France

28–31 January LINC: The Leipzig Interventional Course Leipzig, Germany

www.cacvs.org

www.leipzig-interventional-course. com

26–28 January Conference of the French Society for Wound Care Paris, France

26–27 February Wound Care Today Milton Keynes, UK

www.cictrisations2020.org

www.woundcare-today.com

3–6 March AVF: American Venous Forum Amelia Island, Florida, USA www.veinforum.org

19–21 March Venous Symposium New York, USA www.venous-symposium.com

21–24 April CX Symposium London, UK

30 April–2 May IVC: International Vein Congress Miami, USA

15–16 May VIC: Minimal Invasive Venous Surgery Vienna, Austria

www.ivcmiami.com

www.veinsinternational.com

13–15 May EWMA: European Wound Management Association London, UK

10–12 June RSMVF: Royal Society of Medicine Venous Forum London, UK

www.ewma.org

www.rsm.ac.uk

www.cxsymposium.com

September

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