Endovascular Therapy for Post-Thrombotic Syndrome - A Randomized Trial (C-TRACT)

Clinical Snapshot

Key Findings

• P Value: Primary outcome (VCSS): P=0.001. VEINES-QOL: P<0.001. SF-36 PCS: P<0.001. Bleeding: P=0.03

• Effect Size: Adjusted mean difference in VCSS: -2.0 points (endovascular vs. standard care). VEINES-QOL adjusted difference: +14.5 points. SF-36 PCS adjusted difference: +6.1 points. Bleeding: 11.6% vs. 3.6% (absolute risk increase ~8.0 percentage points)

• Primary Outcome: Venous Clinical Severity Score (VCSS) at 6 months: endovascular therapy group mean 8.1 (±5.1) vs. standard care group mean 10.0 (±4.9); adjusted difference -2.0 points in favour of endovascular therapy

• Nnt Or Sensitivity: NNT cannot be calculated from continuous primary outcome data. For the bleeding harm endpoint: NNH ≈ 13 (based on absolute risk increase of ~8.0 percentage points: 1/0.08 ≈ 13 patients treated to cause one additional bleeding event)

• Confidence Interval: Not reported in the abstract; full manuscript review required

Clinical Application

Iliac-vein stenting is technically feasible in Australian tertiary and quaternary centres with interventional radiology or vascular surgery capability. Appropriate venous imaging (duplex ultrasound, CT venography, or intravascular ultrasound) is required for patient selection. Post-procedural enhanced antithrombotic therapy requires careful management, particularly given the observed bleeding rate of 11.6%. Multidisciplinary team involvement (haematology, vascular medicine, interventional radiology) is recommended for patient selection and peri-procedural anticoagulation management. In Australia, iliac-vein stenting for PTS is performed at select tertiary centres but is not universally available or standardised. There is currently no specific MBS item number for iliac-vein stenting in the PTS indication, and procedural funding pathways may vary by state and institution. Antithrombotic agents used post-stenting (direct oral anticoagulants such as rivaroxaban or apixaban, or warfarin) are PBS-listed for VTE indications, though the 'enhanced' antithrombotic regimen used in C-TRACT may include dual antiplatelet or combination therapy not routinely PBS-subsidised for this indication. The TGA has not issued specific guidance on venous stents for PTS. RACGP and Thrombosis and Haemostasis Society of Australia and New Zealand (THANZ) guidelines do not yet incorporate C-TRACT findings, and clinicians should await guideline updates before widespread adoption. Referral pathways to specialist venous intervention centres should be considered for eligible patients. Adults with moderate-to-severe post-thrombotic syndrome (VCSS-confirmed) and imaging-confirmed iliac-vein obstruction. This population is identifiable in tertiary vascular medicine, interventional radiology, haematology, and vascular surgery clinics. Patients with isolated infrainguinal disease or mild PTS were not studied and results should not be extrapolated to these groups.

Abstract

BACKGROUND: Post-thrombotic syndrome is common after deep-vein thrombosis and can cause severe symptoms involving the limbs that impair patients' activity and quality of life. Endovascular therapy can eliminate chronic venous obstruction and is hypothesized to reduce the severity of post-thrombotic syndrome. METHODS: We randomly assigned 225 patients with moderate or severe post-thrombotic syndrome and imaging-confirmed iliac-vein obstruction to receive endovascular therapy (iliac-vein stent placement and enhanced antithrombotic therapy) plus standard post-thrombotic syndrome care or standard post-thrombotic syndrome care alone. The severity of post-thrombotic syndrome at 6 months (the primary outcome) was assessed with the validated Venous Clinical Severity Score (VCSS) tool (scores range from 0 to 30, with higher scores indicating more severe post-thrombotic syndrome) by evaluators who were unaware of the group assignments. Key secondary outcomes included venous disease-specific and overall quality of life. RESULTS: At 6 months, the severity of post-thrombotic syndrome was lower in the endovascular-therapy group than in the no-endovascular-therapy group (mean [±SD] VCSS, 8.1±5.1 vs. 10.0±4.9; adjusted difference, -2.0; P = 0.001). Venous disease-specific quality of life as assessed with the Venous Insufficiency Epidemiological and Economic Study Quality of Life questionnaire was better in the endovascular-therapy group than in the no-endovascular-therapy group at 6 months (adjusted difference, 14.5 points; P<0.001), as was overall quality of life as assessed with the Medical Outcomes Study 36-Item Short-Form Health Status Survey physical component summary score (adjusted difference, 6.1 points; P<0.001); scores on both tools range from 0 to 100. Through 6 months, bleeding was more common in the endovascular-therapy group than in the no-endovascular-therapy group (in 11.6% vs. 3.6% of the patients; P = 0.03). CONCLUSIONS: Among patients with moderate or severe post-thrombotic syndrome and iliac-vein obstruction, endovascular therapy led to less severe post-thrombotic syndrome and better health-related quality of life than standard care over a 6-month period but with a higher risk of bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; C-TRACT ClinicalTrials.gov number, NCT03250247.).