Randomized Controlled Multicenter Study Comparing Steroid Therapy Plus Anticoagulants to Steroid Therapy Alone in Deep Venous Thrombosis of Behçet's Syndrome (ACTOR)

In patients with Behçet's syndrome (BS), deep venous thrombosis (DVT) is thought to result from inflammation of the vessel wall rather than hyper coagulability.

Post Thrombotic Syndrome (PTS) is frequent especially with recurrent episodes of deep vein thrombosis and may result in leg ulcers that are very difficult to treat. Vascular involvement is a major cause of morbidity and mortality among BS patients. However, one of the most controversial issues regarding the management of BS is whether DVT should be treated with anticoagulants. Moreover, use of anticoagulants exposes patients to serious bleeding, especially in those who presents simultaneous arterial aneurysms. However, many physicians are still using anticoagulants. This is the first prospective, randomized study assessing benefits of corticosteroids associated with anticoagulant compared to that of corticosteroids alone in DVT in BS patients. It will validate or not the use of anticoagulants in those situations. It will allow a direct comparison of the safety profile of those two schemes of treatment.

Study Overview

• Status: Recruiting
• Conditions: Behcet Syndrome
• Intervention / Treatment: Drug: Corticosteroids + Rivaroxaban; Drug: Corticosteroids alone

• Study Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jérôme Lambert, MD PhD; Phone Number: +33 0142499742; Email: jerome.lambert@u-paris.fr
• Study Contact Backup: Name: David Saadoun, MD PhD; Phone Number: +33 0142178042; Email: david.saadoun@psl.aphp.fr

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • CHU BORDEAUX Hôpital Saint-André
    • Contact: Emmanuel Ribeiro; Phone Number: +33 +335 56 79 58 28; Email: Emmanuel.ribeiro@chu-bordeaux.fr
  • Boulogne-Billancourt, France
    • Recruiting
    • Ambroise Paré hospital AP-HP
    • Contact: Georges Selim Trad; Phone Number: +33 +331 49 09 56 42; Email: salim.trad@aphp.fr
  • Caen, France
    • Recruiting
    • CHU caen
    • Contact: Achille Aouba; Phone Number: +33 +332 31 06 45 79; Email: aouba-a@chu-caen.fr
  • Créteil, France
    • Recruiting
    • Hôpital Henri Mondor AP-HP
    • Contact: Nicolas Limal; Phone Number: +33 +331 49 81 20 76; Email: nicolas.limal@aphp.fr
  • Grenoble, France
    • Recruiting
    • CHU de Grenoble
    • Contact: Alban Deroux; Phone Number: +33 +334 76 76 76 40; Email: aderoux@chu-grenoble.fr
  • Le Kremlin-Bicêtre, France
    • Recruiting
    • Hôpital Bicêtre
    • Contact: Nicolas Noel; Phone Number: +33 +331 45 21 27 57; Email: nicolas.noel@aphp.fr
  • Lyon, France
    • Recruiting
    • Hcl, Hopital de La Croix Rousse
    • Contact: Yvan Jamilloux; Phone Number: +33 +334 26 73 26 36; Email: yvan.jamilloux@chu-lyon.fr
  • Melun, France
    • Recruiting
    • Centre Hospitalier de Melun
    • Contact: Nabil Belfeki; Phone Number: +33 +331 81 74 18 87; Email: nabil.belfeki@ghsif.fr
  • Nancy, France
    • Recruiting
    • CHRU DE Nancy Hôpitaux de Brabois
    • Contact: Thomas Moulinet; Phone Number: +33 +333 83 15 42 51; Email: t.moulinet@chru-nancy.fr
  • Nantes, France
    • Recruiting
    • Hôpital Hôtel-Dieu
    • Contact: Olivier Espitia; Phone Number: +33 +332 44 76 80 75; Email: olivier.espitia@chu-nantes.fr
  • Paris, France
    • Recruiting
    • La Pitié Salpêtrière Hospital
    • Contact: David Saadoun, MD PhD; Phone Number: +33 +33142178042; Email: david.saadoun@psl.aphp.fr
  • Paris, France
    • Recruiting
    • Hôpital Saint Antoine AP-HP
    • Contact: Arsène Mekinian; Phone Number: +331 71 97 07 65; Email: arsene.mekinian@aphp.fr
  • Paris, France
    • Recruiting
    • Hôpital Lariboisière AP-HP
    • Contact: Chloé Comarmond; Phone Number: +331 49 95 63 21; Email: chloe.comarmondortoli@aphp.fr
  • Paris, France
    • Recruiting
    • Hôpital Tenon AP-HP
    • Contact: Léa Savey; Phone Number: +33 +331 56 01 67 91; Email: lea.savey@aphp.fr
  • Paris, France
    • Recruiting
    • Hôpital Européen Georges Pompidou AP-HP
    • Contact: Tristan Mirault; Phone Number: +33 +331 56 09 58 32; Email: tristan.mirault@aphp.fr
  • Pessac, France
    • Recruiting
    • CHU Bordeaux- GHU SUD hôpital Haut-Lévêque
    • Contact: Estibaliz Lazaro; Phone Number: +33 +335 57 65 64 83; Email: estibaliz.lazaro@chu-bordeaux.fr
  • Rouen, France
    • Recruiting
    • CHU de Rouen, Hôpital Charles Nicolle
    • Contact: Mathilde Leclercq; Phone Number: +33 +332 32 88 90 03; Email: Mathilde.leclercq@chu-rouen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old
2. Diagnosis of BS according to the international criteria
3. First or recurrent deep venous thrombosis diagnosed on imaging (venous ultrasonography , and/or Angio CT scan and/or angio MRI)
4. Written inform consent
5. Women of childbearing potential (WOCBP) are required to have a negative pregnancy test before treatment and must agree to maintain during treatment highly effective contraception (ie, abstinence, combined estrogen- and progestogen- containing hormonal contraception, ovulation inhibitors (Oral, Intravaginal, Transdermal); Progestogen-only hormonal contraception associated with inhibition of ovulation (Oral, Injectable, Implantable); Intrauterine device (IUD); Intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomised partner).
6. Affiliation to a social security system. Patients affiliated to universal medical coverage (CMU) are eligible for the study

Exclusion Criteria:

1. Clinical condition, other than venous thrombosis, requiring anticoagulation (e.g. atrial fibrillation…)
2. Active bleeding or high risk for bleeding contraindicating treatment with anticoagulants
3. Isolated superficial thrombosis without concomitant deep venous thrombosis.
4. Pregnancy or lactation
5. Have been taking an oral daily dose of a glucocorticoid of more than 20 mg prednisone equivalent for more than 6 weeks continuously prior to the inclusion visit or taking more than 4000 mg methylprednisolone 4 weeks prior to the inclusion visit
6. Have been taking anti-coagulation therapy for more than 4 weeks prior to inclusion
7. Severe chronic renal (creatinine clearance <30ml/min/1,73m2) or liver insufficiency associated with coagulopathy
8. Platelet count < 50 x 103/mm3
9. Change in the treatment with systemic biologic therapy or immunosuppressant therapy dose 1 month prior to inclusion visit.
10. Contraindication to investigational medicinal products (Corticosteroids and direct oral anticoagulant (Rivaroxaban))
11. Participation to another interventional clinical trial or being in the exclusion period at the end of a previous study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Corticosteroids and Rivaroxaban	Drug: Corticosteroids + Rivaroxaban; Corticosteroids according to the schedule of reduction of prednisone (or equivalent prednisone dose only if prednisone is out of stock in the market) and Rivaroxaban
Active Comparator: Corticosteroids alone	Drug: Corticosteroids alone; Corticosteroids according to the schedule of reduction of prednisone (or equivalent prednisone dose only if prednisone is out of stock in the market)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of success	Defined as absence of deep venous thrombosis relapse and of major bleeding event, without introduction of additional immunosuppressive medication for BS activity other than thrombotic events at 6 months.	At 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		At 12 months
Cumulative incidence of deep venous thrombosis and superficial venous thrombosis relapse		At 12 months
Cumulative incidence of major venous thrombosis	pulmonary embolism, vena cava , Budd Chiari syndrome , intra-cardiac relapse	At 12 months
Cumulative incidence of venous repermeabilization	assessed by vascular imaging	At 6 months
Proportion of patients with a dose ≤ 5 mg/day of prednisone	(prednisone or equivalent prednisone dose only if prednisone is out of stock in the market)	At 6 months
Proportion of patients with a dose ≤ 5 mg/day of prednisone	(prednisone or equivalent prednisone dose only if prednisone is out of stock in the market)	At 12 months
Dose of prednisone	(prednisone or equivalent prednisone dose only if prednisone is out of stock in the market)	At 3 months
Dose of prednisone	(prednisone or equivalent prednisone dose only if prednisone is out of stock in the market)	At 6 months
Dose of prednisone	(prednisone or equivalent prednisone dose only if prednisone is out of stock in the market)	At 12 months
Cumulative dose of prednisone	(prednisone or equivalent prednisone dose only if prednisone is out of stock in the market)	At 3 months
Cumulative dose of prednisone	(prednisone or equivalent prednisone dose only if prednisone is out of stock in the market)	At 6 months
Cumulative dose of prednisone	(prednisone or equivalent prednisone dose only if prednisone is out of stock in the market)	At 12 months
Cumulative incidence of major bleeding event		At 12 months
Cumulative incidence of bleeding event		At 12 months
Number of adverse events		At 3 months
Number of adverse events		At 6 months
Number of adverse events		At 12 months
Change in SF-36 quality-of-life	The Short Form (36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability.	At 3 months
Change in SF-36 quality-of-life	The Short Form (36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability.	At 6 months
Change in SF-36 quality-of-life	The Short Form (36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability.	At 12 months
Change in Behçet's Disease Current Activity Form	It is a 7 items score ranging from 0 to 12. The higher the sore the higher the severity of the disease.	At 3 months
Change in Behçet's Disease Current Activity Form	It is a 7 items score ranging from 0 to 12. The higher the sore the higher the severity of the disease.	At 6 months
Change in Behçet's Disease Current Activity Form	It is a 7 items score ranging from 0 to 12. The higher the sore the higher the severity of the disease.	At 12 months
Change in Behçet's Syndrome Assessment Score	It is based on various clinical manifestations of Behçet's disease. Score ranges from 0 to 12. The higher the score the higher the severity of the disease.	At 3 months
Change in Behçet's Syndrome Assessment Score	It is based on various clinical manifestations of Behçet's disease. Score ranges from 0 to 12. The higher the score the higher the severity of the disease.	At 6 months
Change in Behçet's Syndrome Assessment Score	It is based on various clinical manifestations of Behçet's disease. Score ranges from 0 to 12. The higher the score the higher the severity of the disease.	At 12 months
Change in Physician Global Assessment	Evaluation of the disease activity. It ranges from 0 to 10. The higher the score the higher the activity of the disease.	At 3 months
Change in Physician Global Assessment	Evaluation of the disease activity. It ranges from 0 to 10. The higher the score the higher the activity of the disease.	At 6 months
Change in Physician Global Assessment	Evaluation of the disease activity. It ranges from 0 to 10. The higher the score the higher the activity of the disease.	At 12 months
Event free survival		At 12 months
Proportion of post thrombotic syndrome	According to Villalta's post-thrombotic syndrome scale. It assesses the prensece and severity of post thrombotic syndrome. The score ranges from 0 to 30. The higher the score the more severe are the symptoms	At 12 months
Changes in Villalta's post-thrombotic syndrome scale	According to Villalta's post-thrombotic syndrome scale. It assesses the prensece and severity of post thrombotic syndrome. The score ranges from 0 to 30. The higher the score the more severe are the symptoms	At 6 months
Changes in Villalta's post-thrombotic syndrome scale	According to Villalta's post-thrombotic syndrome scale. It assesses the prensece and severity of post thrombotic syndrome. The score ranges from 0 to 30. The higher the score the more severe are the symptoms	At 12 months
Proportion of remission	According to other organs involved	At 3 months
Proportion of remission	According to other organs involved	At 6 months
Proportion of remission	According to other organs involved	At 12 months
Changes in acute-phase reactants		At 1 month
Changes in acute-phase reactants		At 3 months
Changes in acute-phase reactants		At 6 months
Changes in acute-phase reactants		At 12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2025
• Primary Completion (Estimated): December 24, 2027
• Study Completion (Estimated): June 24, 2028

Study Registration Dates

• First Submitted: January 13, 2025
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): January 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Eye Diseases; Skin Diseases; Skin Diseases, Vascular; Skin Diseases, Genetic; Uveal Diseases; Vasculitis; Panuveitis; Uveitis, Anterior; Uveitis; Hereditary Autoinflammatory Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Behcet Syndrome; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Thiophenes; Rivaroxaban; Adrenal Cortex Hormones
• Other Study ID Numbers: APHP220673

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No