利伐沙班用于抗磷脂综合征（RAPS）的方案：一项关于利伐沙班与华法林对比治疗血栓形成性抗磷脂综合征患者（无论是否合并系统性红斑狼疮）的前瞻性、随机对照II/III期临床试验。
Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE.
作者信息
Cohen H, Doré C J, Clawson S, Hunt B J, Isenberg D, Khamashta M, Muirhead N
机构信息
Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK Haemostasis Research Unit, Department of Haematology, University College London, London, UK
University College London Comprehensive Clinical Trials Unit, Gower Street, London, UK.
出版信息
Lupus. 2015 Sep;24(10):1087-94. doi: 10.1177/0961203315581207. Epub 2015 May 4.
INTRODUCTION
The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS.
AIMS
The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin.
METHODS
Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed.
DISCUSSION
If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5.
引言
目前，血栓性抗磷脂综合征（APS）的主要治疗方法是使用维生素K拮抗剂（VKA）如华法林进行长期抗凝。在主要的III期前瞻性随机对照试验（RCT）中，包括利伐沙班在内的非VKA口服抗凝剂（NOACs）已被证明在治疗静脉血栓栓塞（VTE）方面与华法林相比有效且安全，但结果可能无法直接推广至APS患者。
目的
主要目的是在有或无系统性红斑狼疮（SLE）的既往有VTE的APS患者中证明，利伐沙班实现的抗凝强度不低于华法林。次要目的是比较接受利伐沙班治疗的患者与接受华法林治疗的患者的复发性血栓形成、出血发生率及生活质量。
方法
抗磷脂综合征中的利伐沙班（RAPS）是一项II/III期前瞻性非劣效性RCT，符合条件的有或无SLE的APS患者，正在接受华法林治疗，既往VTE的目标国际标准化比值（INR）为2.5，将被随机分为继续使用华法林（对照标准）或改用利伐沙班。将使用凝血酶生成（TG）测试评估抗凝强度，主要结局是从随机分组至第42天内源性凝血酶潜力（ETP）的百分比变化。还将评估其他TG参数、体内凝血激活标志物、凝血酶原片段1.2、凝血酶抗凝血酶复合物和D-二聚体。
讨论
如果RAPS证明：i）利伐沙班的抗凝效果不低于华法林；ii）使用利伐沙班不存在任何引起关注的不良反应，这将提供充分的支持证据，使利伐沙班成为治疗既往有VTE且目标INR为2.5的APS患者的对照标准。
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