Purpose

Objectives

Category

IRB Number
20180178HU
NCT Number
NCT03192215
Sponsor
Columbia University -



Study Contact

Principal Investigator
Reza Behrouz

Charlotte Rhodes
210-450-8454
rhodesc1@uthscsa.edu



Eligibility

Eligible Ages
Over 45 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

    - Age = 45 years. - Clinical diagnosis of ischemic stroke + brain imaging to rule out hemorrhagic stroke. - Modified Rankin Scale (MRS) score = 4. - Ability to be randomized within 3 to 180 days after stroke onset. - ESUS, defined as all of the following: - Stroke detected by CT or MRI that is not lacunar. Lacunar is defined as a subcortical (this includes pons and midbrain) infarct in the distribution of the small, penetrating cerebral arteries whose largest dimension is =1.5 cm on CT or =2.0 cm on MRI diffusion images/<1.5 cm on T2 weighted MR images. The following are not considered lacunes: multiple simultaneous small deep infarcts, lateral medullary infarcts, and cerebellar infarcts. Patients with a clinical lacunar stroke syndrome and no infarct on imaging are excluded. - Absence of extracranial or intracranial atherosclerosis causing =50 percent luminal stenosis of the artery supplying the area of ischemia. Patients must undergo vascular imaging of the extracranial and intracranial vessels using either catheter angiography, CT angiogram (CTA), MR angiogram (MRA), or ultrasound, as considered appropriate by the treating physician and local principal investigator. - No major-risk cardioembolic source of embolism, including intracardiac thrombus, mechanical prosthetic cardiac valve, atrial myxoma or other cardiac tumors, moderate or severe mitral stenosis, myocardial infarction within the last 4 weeks, left ventricular ejection fraction <30 percent, valvular vegetations, or infective endocarditis). Patent foramen ovale is not an exclusion. All patients must undergo electrocardiogram, transthoracic or transesophageal echocardiography (TTE or TEE) and at least 24 hours of cardiac rhythm monitoring (Holter monitor or telemetry or equivalent). Additional cardiac imaging, such as cardiac MRI, or cardiac CT will be performed at the discretion of the local treating physician and principal investigator. Additional cardiac rhythm monitoring, such as monitored cardiac outpatient telemetry (MCOT) or an implanted cardiac monitor, will be at the discretion of the treating physician and local principal investigator. - No other specific cause of stroke identified, such as arteritis, dissection, migraine, vasospasm, drug abuse, or hypercoagulability. Special testing, such as toxicological screens, serological testing for syphilis, and tests for hypercoagulability, will be performed at the discretion of the treating physician and local principal investigator.

Exclusion Criteria

    - History of atrial fibrillation (AF), AF on 12-lead 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.For Canadian sites only, estimated creatinine clearance (eCrCl) <15 mL/min is also an exclusion criterion. - 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: premenopausal or postmenopausal woman within 12 months of last menses without a negative pregnancy test or not committing to adequate birth control, which includes an oral contraceptive, two methods of barrier birth control such as condom with or without spermicidal lubricant + diaphragm, or abstinence. - Known allergy or intolerance to aspirin or apixaban. - Concomitant 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 of either participant or surrogate to provide written, informed consent for trial participation.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Active treatment will be either apixaban 5 mg or aspirin 81 mg. An adjusted dose of apixaban 2.5 mg will be used for subjects with at least two of the following: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or known serum creatinine greater than or equal to 1.5 mg/dL. There will be six possible study tablets: apixaban 5 mg (regular dose), apixaban 2.5 mg (adjusted dose), apixaban 5 mg placebo, apixaban 2.5 mg placebo, aspirin 81 mg, and aspirin placebo. All subjects will be randomized to receive active treatment with either active apixaban or active aspirin. Study treatments will be supplied in a double-dummy fashion as apixaban 5 mg (2.5 mg for the adjusted dose) or matching placebo, and aspirin 81 mg or matching placebo.
Primary Purpose
Prevention
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Eligible patients will be allocated in a 1:1 ratio to apixaban or aspirin using the minimal sufficient balance randomization method to prevent serious treatment imbalances by study site.
Condition
  • Stroke

    • Arm Groups

    ArmDescriptionIntervention
    Experimental

    Active agent: Apixaban

    		Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Apixaban
  • Drug: Apixaban

    5 mg by mouth twice daily (2.5 mg for subjects meeting standard criteria for an adjusted dose).

    Other names:

    • Eliquis

    • Active Comparator

    Active control: Aspirin

    		Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Aspirin
  • Drug: Aspirin

    Aspirin 81 mg by mouth once daily.

    Other names:

    • Aspirin Tablet

    •