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

Официальное название

Immunosuppressive Therapy Alone Versus Immunosuppressive Therapy Plus Oral Anticoagulation in the Treatment of Lower Extremity Venous Thrombosis Associated With Behcet's Disease

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат Placebo plus immunosuppression
  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.
• Препарат Rivaroxaban plus immunosupression
  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.

Первичные конечные точки

• Rate of Thrombotic Relapse at 52 Weeks [Срок оценки: 52 weeks]

Вторичные конечные точки (3)

• Development of Post-Thrombotic Syndrome (PTS) at 52 Weeks [Срок оценки: 52 weeks]
• Rate of Venous Recanalization at 52 Weeks [Срок оценки: 52 weeks]
• Incidence of Major and Clinically Relevant Non-Major Bleeding Events [Срок оценки: 52 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Known coagulation disorders or laboratory abnormalities (e.g., DMID toxicity scale Grade 3 or higher).

History of suicidal behavior in the last 6 months or suicidal ideation (C-SSRS type 4 or 5) in the last 2 months.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Turkey (Türkiye) · 2 центра

• Marmara University, School of Medicine, Division of Rheumatology — Istanbul
• Marmara University — Istanbul

Идентификаторы

NCT: NCT06925698 · 09.2023.1733

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗