Immunosuppressive Therapy Alone Versus Plus Oral Anticoagulation in the Treatment of VT Associated With Behcet's Disease

NCT06925698 | Not Yet Recruiting Phase 3

• 1 other identifier: 09.2023.1733
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Behcet Disease; Behcet Disease and Vascular Involvement; Deep Venous Thromboses; Post Thrombotic Syndrome

Keywords

Behcet's disease; Deep venous thrombosis; Anticoagulant therapy; Rivaroxaban

Outcome Measures

Primary Outcomes (1)

• 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.

  52 weeks

Secondary Outcomes (3)

• Development of Post-Thrombotic Syndrome (PTS) at 52 Weeks

  52 weeks

• Rate of Venous Recanalization at 52 Weeks

  52 weeks

• Incidence of Major and Clinically Relevant Non-Major Bleeding Events

  52 weeks

Study Arms (2)

Immunosuppressive Therapy + Placebo

PLACEBO COMPARATOR

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) + Placebo

Drug: Placebo plus immunosuppression

Immunosuppressive Therapy + Rivaroxaban

ACTIVE COMPARATOR

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), plus Rivaroxaban (20 mg/day, oral, for 12 months)

Drug: Rivaroxaban plus immunosupression

Interventions

Placebo plus immunosuppression DRUG

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.

Immunosuppressive Therapy + Placebo

Rivaroxaban plus immunosupression DRUG

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.

Immunosuppressive Therapy + Rivaroxaban

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must meet the following criteria to be eligible for the study:
• Age between 18-50 years old. Diagnosed with Behçet's Disease according to the International Study Group (ISG) criteria.
• No prior vascular involvement or no previous immunosuppressive therapy for vascular involvement.
• Confirmed venous thrombosis in the lower extremity within the last 14 days before randomization.
• Venous thrombosis diagnosis confirmed by:
• Non-compressible venous segment in ultrasound, OR A significant (\>4 mm) increase in thrombus diameter in an already abnormal segment, OR New intraluminal filling defect on venography, CT, or MR angiography.
• Female participants must:
• Not be pregnant or breastfeeding. Use effective contraception if of childbearing potential. Be postmenopausal (no menses for at least 1 year) or have undergone surgical sterilization.
• Ability to provide written informed consent and comply with study requirements.

You may not qualify if:

• Participants will be excluded if they meet any of the following criteria:
• Presence of any aneurysm. Chronic multisystemic disease other than Behçet's Disease. History of intolerance to Rivaroxaban. Use of immunosuppressive drugs (azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide, TNF inhibitors, or interferon-gamma) within the last 6 months.
• Prolonged corticosteroid use (\>3 months) for Behçet's Disease mucocutaneous symptoms.
• Prior anticoagulant therapy:
• Low molecular weight heparin, fondaparinux, or unfractionated heparin for \>48 hours before randomization.
• More than one dose of vitamin K antagonists before randomization. Thrombectomy, vena cava filter placement, or fibrinolytic therapy for the current thrombotic episode.
• Planned administration of a live vaccine within 30 days after randomization. Clinically significant acute or uncontrolled chronic diseases (e.g., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy, or infectious diseases) that may interfere with study results.
• Planned surgical procedure or significant medical condition deemed unsuitable for the study by the investigator.
• History of malignancy within the last 5 years (except adequately treated basal or squamous cell carcinoma or carcinoma in situ of the cervix).
• Renal impairment (Creatinine clearance \<30 ml/min). Severe liver disease (e.g., acute hepatitis, active chronic hepatitis, cirrhosis, or ALT \>3 times the upper limit).
• Active bleeding or high bleeding risk contraindicating anticoagulant therapy. Uncontrolled hypertension (SBP \>180 mmHg or DBP \>110 mmHg). Severe anemia (Hemoglobin \<10 mg/dL). Women who are pregnant, breastfeeding, or of childbearing potential without contraception.
• Use of strong CYP3A4 inhibitors or inducers (e.g., protease inhibitors, systemic ketoconazole, rifampin, carbamazepine, phenytoin).
• Participation in another experimental drug study within the last 30 days. Life expectancy of less than 3 months. History of serious infections within the last 60 days (e.g., bacterial endocarditis, tuberculosis, opportunistic infections).
• Active substance or alcohol abuse or history of substance dependence within the last year.
• Positive screening for Hepatitis B surface antigen, Hepatitis C antibody, or known HIV-1 infection.

Sponsors & Collaborators

• Marmara University: lead
• Health Institutes of Turkey: collaborator

Study Sites (2)

Marmara University, School of Medicine, Division of Rheumatology

Istanbul, Turkey (Türkiye)

Location

Marmara University

Istanbul, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Behcet Syndrome; Venous Thrombosis; Postthrombotic Syndrome

Interventions

Immunosuppression Therapy; Rivaroxaban; Immune Tolerance

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Eye Diseases; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vascular; Thrombosis; Embolism and Thrombosis; Venous Insufficiency

Intervention Hierarchy (Ancestors)

Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Immune System Phenomena

Study Officials

• Fatma Alibaz-Oner, Prof

  Marmara University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fatma Alibaz-Oner, Prof

CONTACT

+90 216 625 45 45; falibaz@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study follows a double-blind design, ensuring that participants, care providers, investigators, and outcomes assessors are all blinded to the treatment allocation. Randomization and treatment assignment are managed by an independent data monitoring team, which is also responsible for ensuring the integrity of the blinding process. The placebo and active treatment (Rivaroxaban) are identical in appearance, dosage, and administration, minimizing bias. All study-related personnel involved in patient care and outcome assessments remain blinded throughout the study period.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter, prospective, randomized, double-blind, placebo-controlled, Phase III clinical trial designed to evaluate the efficacy and safety of immunosuppressive therapy alone versus immunosuppressive therapy plus oral anticoagulation (Rivaroxaban) in the treatment of venous thrombosis associated with Behçet's Disease. Participants will be randomized (1:1) into two groups: Immunosuppressive therapy alone Immunosuppressive therapy plus Rivaroxaban (20 mg/day, oral) The treatment duration is 12 months, with follow-up visits at weeks 2, 4, months 2, 3, 6, 9, and 12. The study employs a double-blind design, meaning that both participants and investigators are blinded to treatment allocation. Randomization is stratified by gender to ensure balanced distribution. The primary endpoint is the rate of thrombotic relapse within 52 weeks, assessed via venous Doppler ultrasound. Secondary outcomes include post-thrombotic syndrome development, quality of life measures, and safety ass

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: April 13, 2025
• Study Start: April 30, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

TU (2)