RESCUE trial shows reduction in segmental and main pulmonary artery occlusions

Robert A Lookstein, who is executive vice chair, Diagnostic, Molecular and Interventional Radiology at the Icahn School of Medicine at Mount Sinai Hospital (New York, USA) presented the results of a subanalysis of Thrombolex’s National Heart, Lung and Blood Institute (NHLBI)sponsored RESCUE trial during the latebreaking trial session at the Society for Interventional Radiology (SIR) annual scientific meeting (4–9 March, Phoenix, USA).

The core laboratory analysis of this investigational device exemption (IDE) trial demonstrated that pharmacomechanical catheter-directed thrombolysis (PMCDT) therapy using the Bashir endovascular catheter from Thrombolex led to a significant (71%; p<0.0001) reduction in segmental arterial occlusions after treatment, which correlated with the reduction in right ventricular to left ventricular (RV/LV) ratio (p=0.0026). There was also a significant reduction in main pulmonary artery (PA) occlusions (61%; p<0.0001) but this did not correlate significantly with the reduction in RV/LV ratio. The observed reduction in occlusions of both the you can, use a filter when you have to, and get it out as soon as you possibly can”. Johnson acknowledged that there will always be patients who require filtration over a longer period, and in these cases, one might wish to remove the filter if it is “problematic—perhaps penetrating”, to then replace it with a new device.

Rounding off his time on the podium, Johnson asserted his stance on the efficacy of the IVC filter for VTE—“filters do prevent PE; I have no question that this study demonstrated this very well—[there was] a very low incidence of PE in a high-risk population”. He then ventured that where clots do occur in patients with filters placed, it could be that, rather than the filter having caused the clot, that its formation is “linked to patients’ underlying hypercoagulable state and contraindication to anticoagulation. It is not surprising that a person with VTE who cannot be anticoagulated develops another DVT, or a pre-existing DVT progresses. I do not believe that filters cause DVT.”

Rodney White (MemorialCare Long Beach & University of California Los Angeles, Los Angeles, USA) also shared his thoughts with delegates, from the SVS perspective. According to White, the core lab data yielded by the study will help inform guidelines, such as on how best to intervene to treat patients main PAs and the segmental arteries explains why the overall reduction in PA obstruction as assessed by the refined Modified Miller Index is greater with the Bashir endovascular catheter than that which has been reported in contemporary thrombectomy or thrombolysis trials for the treatment of acute pulmonary embolism (PE).

The magnitude of effect of these other treatments on segmental arterial occlusions has not previously been reported.

The RESCUE trial is a prospective, multicentre trial evaluating the Bashir catheter in 109 patients with intermediate-risk acute PE at 18 sites in the USA. Of the 109 participants, 90% had elevated biomarkers and right ventricular dilatation. In the study protocol, the Bashir catheter was used to deliver 7mg of recombinant tissue plasminogen activator (r-tPA) into each PA over a five-hour infusion period, and 94% of patients had bilateral devices placed. The primary efficacy endpoint was the core lab-assessed change in the computed tomography angioplasty (CTA)-derived mean RV/LV diameter ratio at 48 hours (met for 107 patients), and the primary safety endpoint was serious adverse events, including major bleeding, at 72 hours. The median device placement time was 15 minutes, length of hospital stay, 2.8 days, and the number of patients seen at 30-day follow-up, 106.

“The RESCUE trial demonstrated rapid resolution of obstruction in the main, and especially segmental pulmonary arteries, with a <1% major bleeding rate. It is imperative that future endovascular PE trials assess the reduction in obstruction in more distal PAs since it has been shown that both the degree of residual PA obstruction and reduction in pulmonary vascular volumes, presumably due to reduced PA inflow, are significant predictors of late PE-related with an IVC filter. He suggested the data will make it easier to find out “what parameters define filter penetration, what the incidence is, and what the consequences are and how to make it better. It may be that some devices are better than others”. A crucial question is what defines prophylaxis in the current treatment environment, White mused.

A further recommendation from White was that patients with IVC filters placed for VTE have a “dedicated case manager from the time treatment is initiated” so they can “stay in touch with the patient and their family”. Moreover, White made clear the importance of “dedicated IVC filter tracking systems” and filter removal clinics.

Concluding, White informed the audience that Gillespie will be compiling 24-month results for PRESERVE, which will include specific filter analysis, in turn having the potential to impact the definition of ‘prophylactic’ going forward. These longitudinal data will, White averred, “hopefully help [filter] manufacturers report and define indications with the [US] FDA”. Migration penetration will also be continually monitored in study patients, he added, before emphasising the “useful[ness]” of the SIR-SVS collaboration that led to the successful planning and execution of PRESERVE. The value lies, according to White, in being able to “get all stakeholders involved from the mortality. This novel approach with the Bashir catheter and low-dose tPA represents a major advance in the treatment of acute PE,” said Lookstein.

During the late-breaking session at SIR 2023, Lookstein emphasised that the safety profile observed during the trial was “very favourable”. Of note, the presenter added, “even though the Bashir endovascular catheters were selectively delivered preferentially to the lower lobe circulations, the effect of the reduction in pulmonary artery occlusions […] was seen uniformly across the entire pulmonary circulation”. Summarising the mechanisms behind PMCDT therapy with the Bashir catheter, Lookstein proceeded to describe to delegates “the synergistic pharmacomechanical effect of this combination technology, which enhances the luminal gain seen with the activation of the nitinol basket, increasing the surface area of thrombus that is exposed to the fibrinolytic agent, led to greater efficacy. We believe this novel mechanism of action led to an increased number of segmental vessels having restored circulation with this treatment.”

Concluding, Lookstein answered a question about total procedure time, which he stipulated as having been approximately six hours as per protocol. He noted, however, that there may be potential for this to be reduced, but that this would necessitate prospective research in order to be validated. A further comment from one of the delegates present drew attention to the fact that it was “interesting” that RESCUE found the bleeding rate to be “lower” than in some mechanical thrombectomy trials.