In an initial cohort of patients enrolled in the CLEAR-DVT study, contemporary venous intervention resulted in an open vein, which reduced post-thrombotic syndrome (PTS). This is the main concluding finding of a Podium 1st presentation delivered by Mitchell Silver (OhioHealth Heart and Vascular, Columbus, USA) at the 2022 Charing Cross (CX) International Symposium (26–28 April, London, UK).
Silver began by noting that residual venous obstruction is an independent predictor of adverse events, including recurrent venous thromboembolism (VTE), PTS, and venous stent failure. Highlighting the literature on this topic, Silver first outlined the CaVent study—a Norwegian, multicentre, open-label, randomised controlled trial (RCT). This study aimed to examine whether treatment with catheter-directed thrombolysis (CDT) using alteplase reduced the development of PTS in patients with first-time acute iliofemoral deep vein thrombosis (DVT). Silver highlighted 24-month follow-up results, published in The Lancet in 2012, showing that additional CDT should be considered in patients with a high proximal DVT and low risk of bleeding. Silver added that increased patency after six months correlated with reduced development of PTS after 24 months, and that, at five-year follow-up, an absolute risk reduction of 14% after two years increased to 28%.
The speaker highlighted another paper, published in the New England Journal of Medicine in 2017, on pharmacomechanical CDT for DVT. This paper concluded that “among patients with acute proximal DVT, the addition of pharmacomechanical CDT to anticoagulation did not result in a lower risk of the PTS but did result in a higher risk of major bleeding.”
Silver also underlined the ATTRACT trial, noting in particular its limitations. This trial enrolled patients from 2009 and 2014 at over 56 sites. He highlighted the fact that only 1/50 patients screened were actually randomised and that only 57% of patients had iliofemoral DVT. In addition, Silver pointed out that the investigators used standard venography and not intravascular ultrasound (IVUS), median tissue plasminogen activator (tPA) duration was 21 hours, no dedicated venous stents were used; and only 20% of patients had venous duplex at one year. “Treatment, patient selection, and technology have evolved,” Silver remarked.
The speaker communicated that the ATTRACT trial, published in the Journal of Vascular Medicine in 2019, showed that a thrombus-free common femoral vein at one month was associated with improved 24-month clinical outcomes, including PTS, moderate-or-severe PTS, and quality of life (QoL). He also relayed that, in patients presenting with common femoral vein thrombus, successful restoration of full common femoral vein compressibility during the first month was associated with reduced PTS and improved QoL, and possibly also with reduced moderate-or-severe PTS.
Moving on to the CLEAR-DVT study, Silver noted that he is co-principal investigator alongside Stephen Black (St Thomas’ Hospital, London, UK). This investigator-sponsored research (ISR) study is funded by Boston Scientific and the sponsor is Guy’s and St Thomas’ Hospital in London, the presenter noted.
Silver explained that phase one of the CLEAR-DVT study assessed an initial cohort of patients. This first phase represents a proof-of-principle study aiming to validate the hypothesis that contemporary catheter-directed therapy done by experienced operators has significant efficacy and safety. In addition, it seeks to provide objective evidence to move forward with a larger multicentre, prospective randomised controlled versus real-world evidence study.
The investigators enrolled patients from five US and one European site in this initial, single-arm study, Silver told the CX audience. Baseline scores were assessed at 10 days, 30 days, six months, and 12 months, and the study assessed only iliofemoral DVT, up to 14 days. Silver explained that the team used the 8Fr Angiojet ZelanteDVT catheter (Boston Scientific) with on-the-table lysis, and that there is mandated IVUS on all patients. He added that venous stenting was used for more than 50% cross-sectional area reduction and that the post-procedural anticoagulation regimen was standardised to oral anticoagulation for a minimum of six months and plavis (75mg) for the first 60 days.
Addressing the CX audience, Silver detailed that 44% of the 35 patients in the pilot cohort were male and that the average age of the cohort was 48 (range: 22–73). Results on the initial 27 patients at 12-month follow-up show that baseline Villalta was 10 (range: 4–19) and that, after treatment, this had been reduced to two. There was no PTS in 96% of patients and mild PTS in the remaining 4%, with no Villalta score greater than five, Silver pointed out.
The speaker concluded that the CLEAR-DVT study showed that contemporary venous intervention resulted in an open vein, which reduced PTS. Considering next steps, he pointed to one-year data on all patients, which will cover the primary endpoint of PTS rates and secondary endpoints of six-minute walk test, and Venous clinical severity score (VCSS) and QoL scores. Silver also noted that the team are in discussion with industry regarding RCT versus real-world evidence studies on the topics of iliofemoral DVT, new thrombectomy devices, mandated IVUS, and dedicated venous stents.