STUDY TITLE: Chronic Venous Thrombosis: Relief with Adjunctive Catheter-Directed Therapy (The C-TRACT Trial)
CLINICALTRIALS.GOV IDENTIFIER: NCT03250247
SPONSOR: Washington University School of Medicine
ACCRUAL GOAL: 374 patients
PARTICIPATING CENTERS: Multiple sites in the United States (41 centers in total)
STUDY DESIGN: This is a phase III multicenter open-label randomized controlled trial in participants with disabling (moderate-to-severe) post-thrombotic syndrome (PTS) due to previous lower extremity deep vein thrombosis (DVT). Participants will be randomized in a 1:1 ratio to either endovascular therapy (EVT) or non-EVT (control) groups, with all participants receiving standard PTS care (medications, compression stockings, and venous ulcer care). The primary outcome is PTS severity, assessed using the Villalta PTS scale, at six months.
Participants are eligible for inclusion if they have moderate-to-severe post-thrombotic syndrome (based on the presence of a venous ulcer, a venous clinical severity score ≥ 8, or a Villalta score ≥ 10) in a leg with a history of DVT longer than three months ago. Notably, patients must also have radiographic evidence of iliac vein obstruction (occlusion or > 50% stenosis) to be included in the study.
Participants are excluded if they meet any of the following criteria: acute DVT within the previous three months, acute contralateral DVT for which thrombolytic therapy is planned, mild PTS, chronic arterial limb ischemia, previous stent placement in ipsilateral iliac or common femoral vein, presence of open venous ulcer, acute illness, allergy to stent or catheter components, allergy to iodinated contrast refractory to premedication, high risk of bleeding (uncorrectable international normalized ratio > 3.05, platelet count < 75 × 109/L, disseminated intravascular coagulation, bleeding diathesis), a pregnancy, severe renal impairment, life expectancy less than six months, or are chronically nonambulatory.
RATIONALE: PTS is a very common and costly complication of DVT and develops in approximately 40 to 50 percent of patients with proximal DVT despite aggressive medical and interventional therapies.1 PTS can cause major disability, leg ulcers, and impaired quality of life in affected patients.2 As a result, numerous trials, including CaVenT (NCT00251771), ATTRACT (NCT00790335), and CAVA (NCT00970619), have investigated whether the use of EVT in the acute setting can prevent development of PTS, and demonstrated mixed results at long-term follow-up.3-5 For patients who have already developed PTS, however, there are no therapies that have consistently been shown to be effective in improving long-term outcomes. This includes a paucity of data on the use of EVT in patients with disabling iliac vein obstruction resulting in moderate-to-severe PTS (DIO-PTS).
In this study, the authors aim to investigate whether image-guided, endovascular therapy is an effective and safe strategy to reduce post-thrombotic syndrome disease severity.
COMMENT: This study investigates whether EVT can improve morbidity and quality of life in patients with moderate-to-severe PTS, and if so, whether it should be routinely used to treat DIO-PTS. The study is notable for its stringent inclusion criteria, which ensures that only patients with moderate-to-severe PTS who are most likely to benefit from EVT are included in the trial. The involvement of 41 centers across the United States will improve generalizability. Another strength is the use of multiple EVT techniques to optimize outcomes, including iliac vein stenting and various forms of endovenous ablation (e.g., laser ablation, pharmacomechanical ablation).
There are a few limitations to consider with this study. Firstly, patients in the interventional arm may also receive modified antithrombotic therapy, including antiplatelet agents, as part of the intervention alongside EVT. It is not clear if this decision on modified antithrombotic therapies is standardized (i.e., at the discretion of the provider) and as such may introduce bias in the study results. Secondly, the primary outcome of PTS severity is based on assessment of the Villalta score during follow-up at six months. It is, however, worth noting that the reduction in development of PTS and PTS severity in the aforementioned trials was more pronounced at long-term follow-up after more than 12 months.3-5 It is therefore uncertain whether a follow-up duration of six months will be long enough to demonstrate a significant reduction in severity of PTS.
In summary, this important study is one of the first clinical trials designed to address severe established PTS, an exceedingly common, burdensome, and costly complication of DVT. Given the broad disease burden of PTS, the results will have significant implications for the care of patients and will hopefully pave the way for more research in this area.
Dr. Ladha and Dr. Tseng indicated no relevant conflicts of interest.