Clinical trial NCT02926170: Rivaroxaban for Patients With Antiphospholipid Syndrome
Official title: Rivaroxaban Versus Acenocumarol for Secondary Thromboprophylaxis in Patients With Antiphospholipid Syndrome: a Randomized, Prospective, Phase III Study. Analysis of Stratification Prognostic Factors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Antiphospholipid Syndrome
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
First posted: 2016-10-06
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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

Primary outcomes:
measure: Developement of a new thrombotic event (arterial or venous), confirmed by appropiate imaging studies
timeFrame: 36 months
measure: Incidence of major bleeding
timeFrame: 36 months
Secondary outcomes:
measure: Incidence of any treatment-Emergent Adverse events
timeFrame: 36 months
measure: Death due to thrombotic events
timeFrame: 36 months
measure: Time to the first thrombotic event
timeFrame: 36 months
measure: Location of thrombotic events
timeFrame: 36 months
measure: Evaluation of a prognostic biomarker panel
timeFrame: 36 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
Study officials:
affiliation: Vall d'Hebron Research Institute
name: Josefina Cortes, MD,pHD
role: PRINCIPAL_INVESTIGATOR
References: