Rivaroxaban for Patients With Antiphospholipid Syndrome

• ClinicalTrials.gov Identifier: NCT02926170
• Recruitment Status: Completed
• First Posted: October 6, 2016
• Last Update Posted: May 11, 2018
• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Information provided by (Responsible Party): Hospital Universitari Vall d'Hebron Research Institute

Study Description

Brief Summary:

Long-term anticoagulation is widely used for secondary thromboprophylaxis in the antiphospholipid syndrome (APS) due to the high risk of recurrent events. Currently anticoagulation with vitamin K antagonists (VKAs) is the standard of care but have unpredictable pharmacodynamic properties that requiere monitoring for dose adjustment. Rivaroxaban, an orally active direct factor Xa inhibitor, has been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism and non valvular atrial fibrillation in major RCTs. No studies had been published in APS.The aim of the study is to investigate the efficacy and safety of rivaroxaban in preventing recurrent thrombosis in patients with APS compared with acenocoumarol

Condition or disease	Intervention/treatment	Phase
Antiphospholipid Syndrome	Drug: Rivaroxaban; Drug: acenocumarol	Phase 3

Detailed Description:

This is a phase 3 randomized, multicenter, non-inferiority open-label RCT. 190 eligible APS patients with arterial or venous thrombotic history receiving acenocoumarol will be stratified according the presence of SLE and venous/arterial thrombotic history and randomized (1:1) either to continue vitamin K antagonists (standard of care, normalized ratio (INR) 2-3 or 2.5 to 3.5 in those with recurrent thrombotic episodes) or to switch to rivaroxaban (20 mg/day). The primary efficacy outcome is the development of any thrombotic event during the study period. Secondary efficacy outcomes include time to thrombosis, type of thrombosis (arterial or venous), overall causes of death, evaluation of a prognostic biomarker panel of recurrent thrombosis. The primary safety outcome will be major bleeding. Secondary safety outcomes include any adverse event and minor bleeding.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 190 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Rivaroxaban Versus Acenocumarol for Secondary Thromboprophylaxis in Patients With Antiphospholipid Syndrome: a Randomized, Prospective, Phase III Study. Analysis of Stratification Prognostic Factors
• Actual Study Start Date: March 13, 2013
• Actual Primary Completion Date: December 31, 2017
• Actual Study Completion Date: December 31, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: rivaroxaban; Rivaroxaban 20 mg per day	Drug: Rivaroxaban; Rivaroxaban will be started at 20 mg/day. Dose will be adjusted according to Cr Clearance. Cr Clearance 30-49 ml/min will receive 15 mg/day.; Other Name: XARELTO
Active Comparator: acenocumarol; INR adjusted dose	Drug: acenocumarol; Doses will be adjusted according to INR; Other Name: SINTROM

Outcome Measures

Primary Outcome Measures :

1. Developement of a new thrombotic event (arterial or venous), confirmed by appropiate imaging studies [ Time Frame: 36 months ]
   Stroke or transient ischemic attack, myocardial infarction, peripheral arterial thrombosis, cerebral vein thrombosis, deep-vein thrombosis, or pulmonary embolism) that was confirmed by adjudication
2. Incidence of major bleeding [ Time Frame: 36 months ]
   Major bleeding is defined as clinically overt bleeding associated with any of the following: fatal bleeding causing death, involvement of a critical anatomic site (intracranial, spinal, intraocular, pericardial, articular, retroperitoneal, or intramuscular with compartment syndrome) or need for surgery or angiographic intervention to stop haemorrhage, fall in haemoglobin concentration of at least 20 g/L in 24 hours, and/or requiring non-planned transfusion of ≥2 units of packed red blood cells or whole blood

Secondary Outcome Measures :

1. Incidence of any treatment-Emergent Adverse events [ Time Frame: 36 months ]
   i) all adverse events; ii) serious adverse events (SAE); iii) all bleeding events; iv) overall causes of death
2. Death due to thrombotic events [ Time Frame: 36 months ]
   Death as result of a thrombotic event
3. Time to the first thrombotic event [ Time Frame: 36 months ]
   Time (months) from the treatment onset up to the thrombotic event
4. Location of thrombotic events [ Time Frame: 36 months ]
   Location (arterial or venous) whenre the thrombotic event occurred
5. Evaluation of a prognostic biomarker panel [ Time Frame: 36 months ]
   Measuremnt of D-dimer, P-selectine and Von-willebrand factor

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with thrombotic antiphsopholipd syndrome
• Treated with acenocumarol for a minimum period of 6 months
• Positivity for Lupus anticoagulant and/or anti-cardiolipin or anti-B2GPI antibodies IgG or IgM≥40

Exclusion Criteria:

• Major haemorrhage (cerebral or gastrointestinal) within the previous 6 months
• Neurosurgery within the previous 4 weeks
• Any surgery within the previous 10 days
• Active peptic ulcus
• ALT or GPT >120 UI/mL non-lupus related in the previous 30 days
• Platelets <30x10E9 in the previous 30 days
• Recent diagnosed malignancy
• Any criteria listed in the summary of the produt characterisitcs (SPC)
• Renal disease with a creatinine clearance <30 mL/min or with a known uncontrolled renal disease
• Concomitant administration of drugs that could interfere with CYP3A4

Contacts and Locations

Locations

Spain

Vall d'Hebron University Hospital

Barcelona, Spain, 08035

Sponsors and Collaborators

Hospital Universitari Vall d'Hebron Research Institute

Investigators

• Principal Investigator: Josefina Cortes, MD,pHD; Vall d'Hebron Research Institute

More Information

• Responsible Party: Hospital Universitari Vall d'Hebron Research Institute
• ClinicalTrials.gov Identifier: NCT02926170
• Other Study ID Numbers: 2010-019764-36
• First Posted: October 6, 2016
• Last Update Posted: May 11, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Antiphospholipid Syndrome; Syndrome; Disease; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Rivaroxaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants