This study is a Phase III, multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial investigating the treatment of lower extremity venous thrombosis associated with Behçet's Disease. The study compares the effectiveness and safety of immunosuppressive therapy alone versus immunosuppressive therapy combined with oral anticoagulation (Rivaroxaban).
Behçet's Disease is a systemic inflammatory disorder that can cause vascular complications, including venous thrombosis. Although immunosuppressive therapy is the standard treatment for vascular involvement, the role of anticoagulation remains controversial. This study aims to evaluate whether adding Rivaroxaban to standard immunosuppressive treatment reduces the risk of thrombotic relapse and post-thrombotic syndrome compared to immunosuppressive therapy alone. This study is a Phase III, multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial investigating the treatment of lower extremity venous thrombosis associated with Behçet's Disease. The study compares the effectiveness and safety of immunosuppressive therapy alone versus immunosuppressive therapy combined with oral anticoagulation (Rivaroxaban). The study will recruit patients aged 18-50 who have been diagnosed with Behçet's Disease according to International Study Group (ISG) criteria and have a newly diagnosed lower extremity venous thrombosis. Participants will be randomized (1:1) to receive either immunosuppressive therapy with Rivaroxaban or immunosuppressive therapy with a placebo. The treatment duration is 12 months, with follow-up visits at weeks 2, 4, months 2, 3, 6, 9, and 12. The primary outcome is the rate of thrombotic relapse within 52 weeks, assessed by venous Doppler ultrasound. Secondary outcomes include the development of post-thrombotic syndrome (PTS), quality of life measures, and safety assessments, including bleeding complications. The study is sponsored by Health Institutes of Türkiye (TÜSEB) and coordinated by Marmara University, Türkiye. Ethics approval has been obtained from Marmara University Clinical Research Ethics Committee. For further information, please contact the study coordinators.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
110
Participants in this arm will receive placebo plus standard immunosuppressive therapy consisting of: Azathioprine (2.5 mg/kg/day, maximum 200 mg/day, oral) Methylprednisolone (0.5 mg/kg/day, oral, tapered over 12 weeks according to protocol) This intervention represents the standard treatment for venous thrombosis associated with Behçet's Disease and serves as the control arm of the study.
Participants in this arm will receive standard immunosuppressive therapy as described above, plus Rivaroxaban (20 mg/day, oral, for 12 months). This intervention aims to evaluate whether the addition of oral anticoagulation (Rivaroxaban) to immunosuppressive therapy reduces the risk of thrombotic relapse and post-thrombotic syndrome compared to immunosuppressive therapy alone.
Marmara University, School of Medicine, Division of Rheumatology
Istanbul, Turkey (Türkiye)
Marmara University
Istanbul, Turkey (Türkiye)
Rate of Thrombotic Relapse at 52 Weeks
The primary outcome is the rate of thrombotic relapse within 52 weeks, assessed via lower extremity venous Doppler ultrasound. Thrombotic relapse is defined as: A new thrombotic event in a previously unaffected ipsilateral or contralateral vein. Re-thrombosis in a previously affected vein that was classified as well-recanalized (≥50% compressibility on Doppler ultrasound). Venous Doppler ultrasound assessments will be performed at baseline, months 1, 3, 6, 9, and 12.
Time frame: 52 weeks
Development of Post-Thrombotic Syndrome (PTS) at 52 Weeks
The occurrence of Post-Thrombotic Syndrome (PTS) will be assessed using standardized clinical scoring systems, including: Villalta Scale (PTS severity assessment) Venous Clinical Severity Score (VCSS) Venous Disability Score (VDS) Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) PTS is defined as a Villalta score ≥5 or the presence of a venous ulcer.
Time frame: 52 weeks
Rate of Venous Recanalization at 52 Weeks
Venous recanalization will be assessed via Doppler ultrasound to evaluate the extent of clot resolution in affected veins. Partial or complete recanalization will be determined based on compressibility and flow characteristics. Measured at baseline, months 1, 3, 6, 9, and 12.
Time frame: 52 weeks
Incidence of Major and Clinically Relevant Non-Major Bleeding Events
The frequency of major bleeding (as per ISTH criteria) and clinically relevant non-major bleeding will be recorded. Major bleeding: * 2.0 g/dL hemoglobin drop * 2 units of red blood cell transfusion Intracranial, retroperitoneal, or fatal bleeding Clinically relevant non-major bleeding: Epistaxis \>5 minutes, spontaneous hematomas \>25 cm², gastrointestinal bleeding not meeting major criteria.
Time frame: 52 weeks
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