Efficacy and Safety of Prednisone Plus Rivaroxaban Versus Prednisone Alone in Deep Venous Thrombosis of Behçet’s Syndrome: A Randomized Controlled Trial

The primary objective of this study is to assess the **efficacy** and safety of prednisone therapy combined with anticoagulants versus prednisone alone in reducing the rate of relapse of deep venous thrombosis associated with Behçet’s syndrome, without causing major bleeding. This is clinically relevant as it aims to improve treatment outcomes for patients with Behçet’s syndrome, a condition characterized by recurrent venous thrombosis, by potentially offering a more effective therapeutic strategy.

Secondary objectives include:

• Estimating and comparing the cumulative incidence of deep venous thrombosis and superficial venous thrombosis relapse.
• Estimating and comparing the cumulative incidence of major venous thrombosis relapse, including pulmonary embolism, vena cava, Budd-Chiari syndrome, and intra-cardiac thrombosis.
• Estimating and comparing the cumulative incidence of venous repermeabilization.
• Estimating and comparing the steroids sparing effect.
• Estimating and comparing the cumulative incidence of major bleeding events and general bleeding events.
• Estimating and comparing the rate of adverse events.
• Estimating and comparing changes in quality-of-life and Behçet’s syndrome activity.
• Estimating and comparing overall survival and event-free survival.
• Estimating and comparing the rate of post-thrombotic syndrome.
• Estimating and comparing changes in other manifestations of Behçet’s syndrome and acute-phase reactants.

The clinical trial involves participants diagnosed with **Behçet’s syndrome** who have newly diagnosed or relapsing deep venous thrombosis. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a diagnosis of Behçet’s syndrome according to international criteria and must have experienced either a first or recurrent deep venous thrombosis confirmed through imaging techniques such as venous ultrasonography, Angio CT scan, or angio MRI. The trial does not include a vulnerable population. Participants must provide written informed consent and be affiliated with a social security system, including those under universal medical coverage. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed as a **randomized**, **controlled**, multicenter study to evaluate the efficacy and safety of combining steroid therapy with anticoagulants compared to steroid therapy alone in patients with deep venous thrombosis related to Behçet's syndrome. The trial will involve participants aged 18 years and older who have been diagnosed with Behçet's syndrome according to international criteria and have experienced either a first or recurrent deep venous thrombosis confirmed through imaging techniques such as venous ultrasonography, Angio CT scan, or angio MRI. The primary objective is to assess the rate of success, defined as the absence of deep venous thrombosis relapse and major bleeding events without the need for additional immunosuppressive medication over a period of six months following glucocorticoid tapering.

The trial will commence with a screening visit to confirm eligibility based on the inclusion criteria, including written informed consent and social security system affiliation. Participants will be randomly assigned to receive either prednisone therapy plus an anticoagulant or prednisone alone. The trial will be conducted over an estimated duration of four years, with recruitment starting in September 2024 and concluding in May 2028. Participants will be involved in the study for a maximum treatment period of 24 weeks, with follow-up visits scheduled at 3, 6, and 12 months to monitor the cumulative incidence of deep venous thrombosis relapse, major bleeding events, and other secondary endpoints such as venous repermeabilization and quality-of-life changes.

The end-of-study visit will occur at 12 months post-randomization, where final assessments will be conducted to evaluate the overall survival, event-free survival, and remission status according to the involvement of other organs. Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The trial will adhere to rigorous scientific standards to ensure the reliability and validity of the findings, contributing valuable insights into the management of deep venous thrombosis in Behçet's syndrome.

The clinical trial involves the administration of two primary treatments. The first treatment is a **glucocorticoid** administered in a pharmaceutical form identified as PHF00231MIG. The maximum daily dose of this treatment is 40 mg, with a total maximum dose of 2870 mg over a treatment period of up to 24 weeks. The route of administration is oral, and the treatment is classified as a chemical medicinal product. The glucocorticoid is used as a standard-of-care therapy in this study, and participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule.

The second treatment involves the use of **rivaroxaban**, a chemical substance provided in the form of a film-coated tablet. Rivaroxaban is administered orally with a maximum daily dose of 20 mg and a total maximum dose of 3660 mg over a treatment period of up to 6 weeks. An alternative dosing regimen includes a maximum daily dose of 30 mg with a total maximum dose of 630 mg over a treatment period of up to 21 days. Rivaroxaban serves as an anticoagulant in the study, and its administration is carefully monitored to ensure participant compliance and to evaluate its efficacy and safety in combination with glucocorticoid therapy.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is defined as the rate of success, which is the absence of deep venous thrombosis relapse and major bleeding events, without the introduction of additional immunosuppressive medication for Behçet's syndrome venous activity at 6 months, following the tapering of **glucocorticoids**. Secondary endpoints include the cumulative incidence of deep venous thrombosis and superficial venous thrombosis relapse within 12 months from randomization, as well as the cumulative incidence of major venous thrombosis relapse within the same period. Additionally, the cumulative incidence of venous repermeabilization will be assessed by vascular imaging at 6 months, using specific ultrasound criteria to determine the absence of repermeabilization flow.

Further secondary endpoints involve measures of corticosteroid sparing, such as the proportion of patients with a dose ≤ 5 mg/day of prednisone at 6 and 12 months, and the cumulative dose at 3, 6, and 12 months. The trial will also evaluate the cumulative incidence of major bleeding events and other bleeding events within 12 months from randomization. Adverse events will be recorded at 3, 6, and 12 months. Changes in quality of life will be measured using the SF-36 scale at 3, 6, and 12 months from baseline. Changes in Behçet's Disease activity scores, including BDCAF, BSAS, and Physician Global Assessment (PhGA), will be monitored at 3, 6, and 12 months. The trial will also assess overall survival and event-free survival within 12 months from randomization, the proportion of post-thrombotic syndrome according to Villalta’s scale, and changes in acute-phase reactants at 1, 3, 6, and 12 months.