Anticoagulation Withdrawal in Antiphospholipid Syndrome

描述（由申请方提供）：抗磷脂综合征（APS）是一种罕见的疾病，其特征为静脉和/或动脉血栓栓塞（TE）或复发性妊娠丢失，抗磷脂抗体水平持续升高。抗凝治疗被认为是大多数APS和TE患者的治疗选择，尽管一些权威机构认为抗血小板治疗可能是APS和动脉TE患者的可接受替代治疗。还建议APS和TE患者在初始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复发风险显著增加无关。然而，长期抗凝治疗并不是良性的，出血性并发症对无限期抗凝治疗的患者来说是一个重大的危险。我们假设有很大比例的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、随机临床试验，即抗磷脂综合征中的Warpose戒断研究（WAR-APS），该研究将实现以下两个目的。首先，我们将确定已完成标准抗凝治疗疗程（e3个月）的APS和VTE患者是否可以安全地停止抗凝治疗。患者将随机接受继续抗凝治疗或停止抗凝治疗并开始阿司匹林抗血小板治疗。其次，我们将确定接受抗凝治疗（e3个月）的APS和卒中或短暂性脑缺血发作患者是否可以安全地停止抗凝治疗。与第一个目标一样，患者将随机分配至继续抗凝治疗或转为阿司匹林抗血小板治疗。本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静脉事件患者的TE复发风险，我们将根据患者的首次事件是静脉还是动脉将患者分为两组，我们将考虑抗凝治疗作为一种“类别”治疗，将华法林与新的口服抗凝剂相结合。这项赠款申请的主要目的是实施规划委员会和完成所有启动活动，这些活动必须在审判本身开始之前完成。授予期间要完成的目标包括：（1）完成方案，包括最终确定样本量、入选/排除标准以及主要和次要结局的标准;（2）制定并最终确定病例报告表;（3）建立所有研究相关委员会;（4）确定参与研究的研究中心，并在研究开始前完成IRB提交文件和合同;（5）确定抗凝治疗管理核心并最终确定盲法治疗管理策略;（6）获得实验室试剂和治疗剂的行业支持;（7）最终确定所有统计分析。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.