“A very grey area”: EVOCC trial addresses best treatment option for aortoiliac disease

Athanasios Saratzis (University of Leicester, Leicester, UK) speaks to Vascular News about the EVOCC (Endovascular versus open revascularisation in severe occlusive aortoiliac disease) trial. This randomised study recently received funding from the UK’s National Institute for Health and Care Research (NIHR), marking the first step in what Saratzis states will be “one of the largest peripheral arterial disease [PAD] trials in the UK over the next few years”.

What is the rationale behind this randomised trial?

This was really a patient-initiated study. In Leicester, a lot of our patients feel that there is uncertainty surrounding treatment decisions for those who have severe aortoiliac disease, with regards to how it is decided whether open surgery or endovascular surgery is better. We realised about two or three years ago that there is actually no literature on this. We do not really know whether the results of open surgery are better compared to endovascular treatment, and we do not really know which endovascular surgery or endovascular treatment is the best one in terms of which stents to use and how you use them. Against this backdrop, we performed a meta-analysis that was a joint project between our centre in Leicester and St Thomas’ Hospital in London, UK. We looked at the few studies that have been published in this domain, and found out that actually modern endovascular techniques are probably as good as open surgery, at least for the first few months. However, there is not much data available on what happens after the first three months, especially with regards to reinterventions or late clinical events. When we applied for funding to the NIHR, it was decided that this was an important project, and here we are.

How would you describe the current landscape of care for severe aortoiliac disease across the UK?

In order to design the study, we sent out a national survey to which 144 interventional radiologists and vascular surgeons replied. We also involved 28 patients nationally who had some form of treatment for this condition in order for us to understand what the treatment landscape is like. About 80% of the surgeons and radiologists who took part in the survey were in agreement that we do not really know whether open surgery is better than modern endovascular treatments in this setting; about 95% felt that we need to do a randomised trial in order to compare modern endovascular treatments and the traditional type of surgery that we have been offering to patients. The patients were all in agreement that they would take part in a study as long as the treatments were safe. Our survey showed that there are still some centres that have got a preference for open surgery and some other centres might have a preference for endovascular surgery, but none of that is actually based on very strong evidence.

How many patients do you hope to enrol and what is the timeline?

This will be a difficult study because of the fact that patients with chronic limb-threatening ischaemia (CLTI) are often frail, which means that it is not very easy to ask them to take part in studies and sometimes decision-making for these patients can be complex. Therefore, I am not expecting that it will be an easy study to complete. In order for us to compare the two treatments in terms of our primary outcome of amputation-free survival, we need to recruit 628 patients. We aim to do this over a period of about 30 months. An internal pilot study, which will start in October 2023, is the first phase of the trial, and that will go on for at least six months. Following that, we will open our main recruitment phase, which will last two years. We are going to follow every patient up

Medtronic announces first enrolment in head-to-head global randomised trial evaluating durability of EVAR

Medtronic has announced the first patient enrolment in the ADVANCE (Endurant stent graft system versus Excluder endoprosthesis) trial, a head-to-head randomised controlled trial of two leading aortic stent graft systems, the Endurant II/IIs stent graft system (Medtronic) and Excluder AAA device family systems (Gore). The ADVANCE trial is a global, post-market, prospective, interventional, multicentre, randomised study that will enrol a minimum of 550 patients at up to 50 centres globally. Patients will be randomised to receive endovascular aneurysm repair (EVAR) with either the Endurant family or Excluder family grafts and will be followed at one month, one year, and annually through five years.

THE FIRST PATIENT IN THE ADVANCE trial was enrolled by the team led by Ray Workman at Novant Health Forsyth Medical Center (Winston-Salem, USA).

“Through the ADVANCE trial, we are working to deepen our evidence of sac regression as a key indicator of long-term EVAR patient outcomes,” said Hence Verhagen (Erasmus Medical Center, Rotterdam, The Netherlands), co-principal investigator of the trial.

Athanasios Saratzis

for at least two years and for a median of three years. It is our hope that 30 sites (hospitals across the NHS) will take part in the trial. So far, we have been in touch with 35 sites, most of which have confirmed that they would like to participate. It will take a few years before we know the results of the study because it is a big project. I think the internal pilot will give us a lot of interesting information and then hopefully we will be able to recruit the 600 patients we need for the main study.

What do you expect from this trial?

Do you have an idea of how the results might play out?

Not really! If you asked me a few months ago, I would have said that endovascular treatments are definitely seeing major improvements. However, the BEST-CLI trial report from the USA clearly shows that for CLTI patients with disease below the inguinal ligament, surgery seems to do a bit better. So, I am not sure whether we will see the same signal in patients with aortoiliac disease. I think there is just so much uncertainty, and in fact the BEST-CLI results have confirmed even more the fact that we need to do this trial. I am an endovascular enthusiast, but increasingly I am becoming more and more uncertain as to which treatment is the best one. It is a very grey area, let me put it that way.

On the topic of BEST-CLI, how do you think the results might impact the landscape of vascular trials going forward?

I think BEST-CLI is a turning point in vascular surgery, especially in PAD, because we are now funding more effectiveness trials like this one. We really need the support of all vascular clinicians in order to recruit to those studies efficiently in the years to come. It is borderline unacceptable to offer complex endovascular treatments to patients with vascular diseases and not recruit into big effectiveness trials assessing these treatments. There are clearly many questions that have not been answered, and these are not my questions, they are questions that the patients bring up and impact on their care.

“Our hope is that the findings will allow physicians to make evidence-based clinical decisions to improve long-term patient outcomes.”

The ADVANCE trial aims to further the understanding of sac regression by robust evaluation of CT imaging utilising an independent core lab through five years. The trial will provide a comparison of aneurysm sac regression outcomes between the Medtronic Endurant II/IIs stent grafts and the Gore Excluder AAA device family stent grafts with additional evidence to analyse risk factors related to aneurysms that fail to regress. The trial will also compare other key clinical outcomes between the two stent grafts, including endoleaks, migration, secondary interventions, mortality, and renal complications.

“We are pleased to announce the first patient enrolled in the ADVANCE

Endurant

trial,” said Marc Schermerhorn, chief of vascular and endovascular surgery, Beth Israel Deaconess Medical Center (Boston, USA) and co-principal investigator of the trial. “This milestone underscores the commitment to rigorous study of the long-term data around the durability of the Endurant system for patients in need of EVAR. The results of the trial aim to demonstrate contemporary outcomes and our overarching goal to deliver superior aortic patient care through robust and rigorous clinical data.”

The ADVANCE trial draws on clinical data showing that one-year sac regression is an early indicator of improved long-term survival. The outcomes were consistent with the eight-year results from the ENGAGE OUS registry, published in January 2022, which demonstrated the long-term clinical safety and effectiveness of the Endurant stent graft system.

SWING trial 12-month data: Novel sirolimus DCB shows “great promise” in “challenging” CLTI population

The Sundance (Surmodics) sirolimus drug-coated balloon (DCB) has an “excellent” safety profile in a “challenging, realworld, predominantly CLTI [chronic limb-threatening ischaemia] population,” and has a primary patency rate of 80% at 12 months in a per-protocol analysis population. Ramon Varcoe (Prince of Wales Hospital, Sydney, Australia) first presented these findings from the SWING (Safety and feasibility of Surmodics Sundance DCB) first-in-human study at the 2022 VEITHsymposium (15–19 November, New York, USA).

VARCOE, WHO IS CO-LEAD investigator of the trial, added that the research team observed no major amputations, “very low” rates of major adverse events, and “impressive” luminal gain, which was sustained out to six-month angiogram. In addition, Varcoe reported that Rutherford category and the functional outcome measures were improved.

The presenter noted that SWING is a prospective, multicentre, single-arm feasibility study that looked at patients with stenotic or occluded lesions. The researchers enrolled 35 patients over eight sites in Australia, New Zealand, and also in Europe.

Noting some key inclusion criteria,

Varcoe detailed that patients had to be either Rutherford 4 or 5. He added the caveat that Rutherford 3 patients were included, but numbers were capped at 20% of the total cohort. Furthermore, patients had to have de novo or restenotic lesions and at least 50% stenosis by visual estimate of the investigator. They could have up to two distinct lesions in the same or different below-the-knee (BTK) artery, and had to have successfully treated inflow, as well as an unimpaired outflow artery in continuity to the ankle or foot.

The investigators performed both an intention-to-treat and a per-protocol analysis, Varcoe informed the audience.

“The reason for that was because [the trial] was conducted over the COVID-19 pandemic period, so we lost seven patients to the primary endpoint of angiography,” he noted, adding that there were also three post-protocol deviations. For these reasons, the research team focused on the 25 patients who had the perprotocol analysis.

The presenter stressed that the patients included represent a “realworld” population, including a high proportion of patients who are smokers and have diabetes, as well as a majority of patients with Rutherford 4 or 5 disease. “They also had high proportions of moderate-to-severe calcification in excess of 18%, and around a third of these patients had total occlusions,” he added.

The study had two primary endpoints. The first was a safety primary safety endpoint—freedom from major adverse limb event (MALE) and perioperative death at 30 days following the index procedure. The primary efficacy endpoint was the rate of late lumen loss at six months, as assessed by quantitative vascular angiography.

Both primary endpoints of the SWING trial were achieved, Varcoe revealed. Varcoe reported that, in the per-protocol population, there were no major amputations, no major reinterventions, and complete freedom from perioperative death, “so it was a safe device”. The team also saw a rate of all-cause death that was 0%, target lesion amputations were 0%, and a “very low” rate of clinically driven target lesion revascularisation at 8%. Varcoe added that the minimal luminal diameter at the end of the procedure was “very high”, which he thinks “represents modern-day angioplasty techniques”, and reported a late lumen loss of 1mm at six months— results that compare “very favourably” to other equivalent DCB trials below the knee, he remarked.

At six months, the researchers observed a primary patency of 88.5%. Varcoe noted that primary patency was retained and consistently retained out to 12 months at 80%—a figure that he said is “very good for this part of the vasculature”.

Varcoe added that, “pleasingly,” the team also saw improvement in Rutherford Becker classification, which was sustained and improved out to 12 months. Regarding quality of life, he noted that patient-reported outcome measures were again consistently improved out to that 12-month endpoint.

In closing, Varcoe shared his belief that the Sundance device has “great promise” and “warrants evaluation in a large-scale pivotal trial” based on these latest findings.

CAGENT VASCULAR HAS ANNOUNCED THE RESULTS OF A comparative subanalysis of the PRELUDE-below-the-knee (BTK) study versus plain balloon angioplasty. The study was led by Marianne Brodmann (Medical University of Graz, Graz, Austria). This subanalysis compared their PRELUDEBTK subset to a consecutive plain balloon angioplasty group.

The Serranator-treated lesions had an average final residual stenosis of 17.2±8.2% vs. 33.7±15.7% in the plain balloon angioplasty group. This represents a 49% average improvement in final residual stenosis. In chronic total occlusions (CTO), there was a 62% improvement in final residual stenosis compared to the plain balloon angioplasty group. The average balloon inflation pressure was 5atm in the Serranator group vs. 9atm in the conventional balloon angioplasty group. Additionally, Serranator-treated arteries demonstrated 2.4 times greater calculated flow improvement versus plain balloon angioplasty These data, analysed by the same independent core lab, were recently published in the Journal of Endovascular Therapy

Brodmann stated: “As an early user of serration angioplasty, it was meaningful to quantify through this subanalysis what we have experienced using the Serranator device. William Tang (UC Irvine, Irvine, USA) developed a novel model, anchored by Poiseuille’s law, from which we were able to derive the volumetric blood flow from lumen gain achieved with the Serranator compared to conventional balloon angioplasty. These results suggest an advantage for serration technology that should allow for superior wound healing and patient outcomes, while minimising the need for stent placement.”

Raman Sharma (Mount Sinai Medical Center, New York, USA) was an early adopter of serration technology, and added: “The results from this subanalysis study support what we have seen in our experience; the Serranator provides greater lumen gain and blood flow versus conventional technology.”

Surmodics provides regulatory update related to its FDA premarket approval application for SurVeil

SURMODICS RECENTLY announced it has received a letter from the US Food and Drug Administration (FDA) related to its premarket approval (PMA) application for the SurVeil drugcoated balloon (DCB). In the letter, the FDA indicated that the application is not currently approvable, while providing specific guidance as to a path forward. The letter stated that certain information within two general categories— biocompatibility and labelling—must be added by an amendment to the company’s PMA application to place it in approvable form. Although the information identified by the FDA to put the PMA application in approvable form would require additional testing and analysis, the letter did not question the human clinical data submitted.

“We are disappointed by the FDA’s response to our PMA application and continue to have confidence in our SurVeil DCB including its compelling performance in the TRANSCEND clinical study,” said Gary Maharaj, CEO of Surmodics. “We are evaluating the issues raised in the FDA’s letter and plan to meet with Agency representatives regarding its contents. Based on our discussion with the Agency, our team and external advisors will determine the appropriate path forward. Concurrently, we will be evaluating options to reduce our use of cash given this development. We expect to address these topics further in connection with our upcoming first quarter fiscal 2023 earnings call.” Surmodics notes in a press release that the SurVeil DCB is a nextgeneration device for the treatment of peripheral arterial disease.