Anticoagulation Withdrawal in Antiphospholipid Syndrome

描述(申请人提供)：抗磷脂综合征(APS)是一种罕见的疾病，其特征是静脉和/或动脉血栓栓塞症(TE)，或反复妊娠丢失，存在持续升高的抗磷脂抗体水平。抗凝治疗被认为是大多数APS和TE患者的首选治疗方法，尽管一些权威人士建议，对于APS和动脉TE患者，抗血小板治疗可能是一种可接受的替代方案。还建议APS和TE患者在最初事件后接受无限期抗凝治疗，即使最近的分析表明，抗磷脂抗体的存在与TE复发的风险并不显著相关。然而，长期的抗凝治疗并不是良性的，出血性并发症对致力于无限期抗凝的患者来说是一个重大的危险。我们假设，相当大比例的APS和TE患者不需要长期抗凝治疗。为了解决这一假设，我们提出了一项前瞻性、双盲、随机的临床试验，即华法林停药抗磷脂综合征研究(WAR-APS)，它将实现以下两个目标。首先，我们将确定完成了标准抗凝疗程(E3个月)的APS和VTE患者是否可以安全地停止抗凝治疗。患者将被随机分成两组，要么继续抗凝治疗，要么停止抗凝，开始阿司匹林抗血小板治疗。其次，我们将确定接受了抗凝治疗(E3个月)的APS合并中风或短暂性脑缺血发作的患者是否可以安全地停止抗凝。与第一个目标一样，患者将被随机分成两组，要么继续抗凝治疗，要么改用阿司匹林抗血小板治疗。这项研究的创新方面包括，我们将使用几种策略来最大限度地降低有静脉事件的患者复发TE的风险，我们将根据患者的第一次事件是静脉事件还是动脉事件将患者分成两组，我们将把抗凝治疗视为一类治疗，将华法林与新型口服抗凝剂相结合。这项赠款申请的主要目的是执行规划委员会，并完成在审判本身开始之前必须最后确定的所有启动活动。获奖期间要完成的目标包括：(1)完成方案，包括最终确定样本数量、纳入/排除标准以及主要和次要结果的标准；(2)开发和最终确定病例报告表；(3)建立所有与研究相关的委员会；(4)确定参与研究的地点，并在研究开始前完成IRB提交的文件和合同；(5)确定抗凝治疗管理核心并最终确定管理盲目治疗的战略；(6)获得业界对实验室试剂和治疗试剂的支持；以及(7)完成所有统计分析。我们将与临床试验开发资源合作完成这些目标，这将使我们能够成功地进行WAR-APS试验。

DESCRIPTION (provided by applicant): Antiphospholipid syndrome (APS) is a rare disorder characterized by venous and/or arterial thromboembolism (TE), or recurrent pregnancy loss, in the presence of persistently elevated antiphospholipid antibody levels. Anticoagulant therapy is considered the treatment of choice for most patients with APS and TE, although some authorities suggest that antiplatelet therapy may be an acceptable alternative for patients with APS and arterial TE. It is also recommended that patients with APS and TE receive indefinite anticoagulant therapy following an initial event, even though recent analyses would suggest that the presence of an antiphospholipid antibody is not associated with a significantly increased risk for recurrent TE. Long-term anticoagulant therapy is not benign, however, and hemorrhagic complications represent a significant hazard for patients committed to indefinite anticoagulation. We hypothesize that a significant proportion of patients with APS and TE do not require long-term anticoagulant therapy. To address this hypothesis, we are proposing a prospective, double- blind, randomized clinical trial, the Warfarin Withdrawal in Antiphospholipid Syndrome Study (WAR-APS), which will accomplish the following two Aims. First, we will determine whether patients with APS and VTE who have completed a standard course of anticoagulant therapy (e3 months) can safely discontinue anticoagulation. Patients will be randomized to either continue anticoagulant therapy or discontinue anticoagulation and begin antiplatelet therapy with aspirin. Second, we will determine whether patients with APS and stroke or transient ischemic attack who have been treated with anticoagulant therapy (e3 months) can safely discontinue anticoagulation. As with the first Aim, patients will be randomized to either continue anticoagulant therapy or switch to antiplatelet therapy with aspirin. Innovative aspects of this study include that we will use several strategies to minimize the risk for recurrent TE in patients with venous events, that we will stratify patients into two groups according to whether their first event was venous or arterial, and that we will consider anticoagulant therapy as a "class" of therapy, combining warfarin with the new oral anticoagulants. The primary purpose of this grant application is to implement the Planning Committee and complete all start-up activities that must be finalized before the trial itself can begin. Objectives to be accomplished during the award include: (1) completion of the protocol, including finalizing sample size, inclusion/exclusion criteria, and criteria for primary and secondary outcomes; (2) develop and finalize the case report forms; (3) establish all study-related committees; (4) identify participatng study sites and complete IRB submissions and contracts prior to study opening; (5) identify the anticoagulant therapy management core and finalize strategies for managing the blinded therapies; (6) obtain industry support for laboratory reagents and therapeutic agents; and (7) finalize all statistical analyses. We will work with the Clinical Trials Development Resource to complete these objectives, which will position us to successfully conduct the WAR-APS trial.