Rivaroxaban Versus Acenocumarol for Secondary Thromboprophylaxis in Patients With Antiphospholipid Syndrome: a Randomized, Prospective, Phase III Study. Analysis of Stratification Prognostic Factors
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 190
- 试验地点
- 1
- 主要终点
- Incidence of major bleeding
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
rivaroxaban
Rivaroxaban 20 mg per day
干预措施: Rivaroxaban (Drug)
acenocumarol
INR adjusted dose
干预措施: acenocumarol (Drug)
结局指标
主要结局
Incidence of major bleeding
时间窗: 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
Developement of a new thrombotic event (arterial or venous), confirmed by appropiate imaging studies
时间窗: 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
次要结局
- Death due to thrombotic events(36 months)
- Incidence of any treatment-Emergent Adverse events(36 months)
- Location of thrombotic events(36 months)
- Time to the first thrombotic event(36 months)
- Evaluation of a prognostic biomarker panel(36 months)