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.

Public Health Relevance

Antiphospholipid syndrome (APS) is a rare disorder characterized by recurrent thromboembolic events and/or pregnancy-related complications. Most authorities recommend that patients with APS and thromboembolic events receive anticoagulant therapy indefinitely. Several recent reports would suggest that this recommendation is not correct, however. This planning grant will be developing a prospective, randomized, double-blind clinical trial, the Warfarin Withdrawal in Antiphospholipid Syndrome (WAR-APS) study, which will determine whether indefinite anticoagulation is appropriate for all patients with APS. (End of Abstract)

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Planning Grant Cooperative Agreement (U34)
Project #
1U34HL123499-01
Application #
8752153
Study Section
Special Emphasis Panel (ZHL1-CSR-C (M2))
Program Officer
Kindzelski, Andrei L
Project Start
2014-08-05
Project End
2017-06-30
Budget Start
2014-08-05
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$251,131
Indirect Cost
$91,175
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705