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

April 7, 2025 updated by: Marmara University

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
110

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Fatma Alibaz-Oner, Prof
  • Phone Number: +90 216 625 45 45
  • Email: falibaz@gmail.com

Study Locations

  • Turkey
      • Istanbul, Turkey
        • Marmara University
      • Istanbul, Turkey
        • Marmara University, School of Medicine, Division of Rheumatology
        • Contact:
        • Contact:
          • Fatma Alibaz Oner, Prof
        • Contact:
          • Kerem Abacar, MD
        • Contact:
          • Haner Direskeneli, Prof
        • Contact:
          • Ahmet Gül, Prof
        • Contact:
          • Cemal Bes, Prof
        • Contact:
          • Ayten Yazici, Prof
        • Contact:
          • Ömer Karadağ, Prof
        • Contact:
          • Mehmet Akif Öztürk, Prof
        • Contact:
          • Ahmet Omma, Ass. Prof

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Immunosuppressive Therapy + Placebo
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

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.
Active Comparator: Immunosuppressive Therapy + Rivaroxaban
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

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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of Thrombotic Relapse at 52 Weeks
Time Frame: 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Development of Post-Thrombotic Syndrome (PTS) at 52 Weeks
Time Frame: 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.
52 weeks
Rate of Venous Recanalization at 52 Weeks
Time Frame: 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.
52 weeks
Incidence of Major and Clinically Relevant Non-Major Bleeding Events
Time Frame: 52 weeks

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.
52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Marmara University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Health Institutes of Turkey

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Fatma Alibaz-Oner, Prof, Marmara University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 7, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 13, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 13, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 09.2023.1733

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data (IPD) will not be shared to ensure patient confidentiality and compliance with data protection regulations

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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