The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is looking for individuals to participate in clinical studies. Participating in clinical trials allows you to play an active role in research on the nature and causes of many disorders of the brain and nervous system, and to possibly help physician-scientists develop future treatments. The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible.

Description:

The purpose of this trial is to compare two different blood-thinning drugs—apixaban and aspirin—to determine which is better for preventing recurrent stroke in people who have cryptogenic stroke (stroke of unknown cause) and atrial cardiopathy (abnormal changes in the atrial tissue and function of the heart).

In one-third of ischemic strokes, a specific cause cannot be identified.  Recent evidence suggests that some cryptogenic strokes are caused by a blood clot (thromboembolism) in the left atrium of the heart that goes unrecognized because it is not associated with atrial fibrillation (AF).  Generally, it is thought that AF must be present for blood clots to form in the left atrium.  However, recent research shows that blood clots can occur when there is atrial cardiopathy, even before there is AF.  This may explain many of the strokes that are currently of unknown cause.  Since anticoagulant drugs such as apixaban have already proven more effective than standard aspirin therapy for preventing stroke from AF, apixaban also may be more effective than aspirin for stroke prevention in people with atrial cardiopathy with no AF.

ARCADIA is a multi-center, randomized, double-blind clinical trial of apixaban versus aspirin in people who have evidence of atrial cardiopathy and a recent stroke of unknown cause.

The trial will recruit 1100 participants over 2.5 years at 150 sites within the NIH StrokeNet consortium (http://www.nihstrokenet.org/).  Participants will be randomized into 1 of 2 groups.  Group 1 will receive 81 mg of aspirin plus a placebo (inactive) pill twice a day.  Group 2 will receive 5 mg of apixaban twice a day plus a placebo pill once a day (with reduced dose of 2.5 mg apixaban twice daily for those who meet criteria defined by age, weight and creatinine levels).  After the initial eligibility and randomization visits, participants will have additional follow-up visits at 3, 6, 9, and 12 months, and every 6 months for a maximum of 4 years.

Information gained from this study will help researchers learn more about cardiac risk factors for stroke which may improve risk factor screening and stroke prevention efforts and, in so doing, reduce the incidence of stroke.

Eligibility Criteria:

Key Criteria:

Inclusion:

  • Age ≥ 45 years.
  • Clinical diagnosis of ischemic stroke plus brain imaging to rule out hemorrhagic stroke.
  • Modified Rankin Scale (MRS) score ≤ 4.
  • Ability to be randomized within 3 to 120 days after stroke onset.
  • Embolic stroke of undetermined source (ESUS), defined as all of the following:
    • Non-lacunar stroke detected by computed tomography (CT) or magnetic resonance imaging (MRI).
    • Absence of extracranial or intracranial atherosclerosis causing ≥50 percent luminal stenosis of the artery supplying the area of ischemia.
    • No major-risk cardioembolic source of embolism, including intracardiac thrombus, mechanical prosthetic cardiac valve, atrial myxoma or other cardiac tumors, mitral stenosis, myocardial infarction within the last 4 weeks, left ventricular ejection fraction <30 percent, valvular vegetations, or infective endocarditis.
    • No other specific cause of stroke identified, such as arteritis, dissection, migraine, vasospasm, drug abuse, or hypercoagulability.

Exclusion:

  • History of atrial fibrillation (AF), AF on 12-lead electrocardiogram (ECG), or any AF of any duration during heart-rhythm monitoring prior to randomization.
  • Clear indication for treatment-dose anticoagulant therapy, such as venous thromboembolism or a mechanical heart valve.
  • Need for antiplatelet agent, such as aspirin or clopidogrel.
  • History of spontaneous intracranial hemorrhage.
  • Chronic kidney disease with serum creatinine ≥2.5 mg/dL.
  • Active hepatitis or hepatic insufficiency with Child-Pugh score B or C.
  • Clinically significant bleeding diathesis.
  • Unresolved anemia (hemoglobin <9 g/dL) or thrombocytopenia (<100 x 10E9/L).
  • Clinically significant gastrointestinal bleeding within the past year (e.g., not due to external hemorrhoids).
  • At risk for pregnancy.
  • Known allergy or intolerance to aspirin or apixaban.
  • Participation in another clinical trial involving a drug or acute stroke intervention.
  • Considered by the investigator to have a condition that precludes follow-up or safe participation in the trial.
  • Inability to provide written, informed consent for trial participation.

Study Design:

randomized
double-blind
active-control