Purpose

Primary Aim: To determine if apixaban is superior to aspirin for prevention of the composite outcome of any stroke (hemorrhagic or ischemic) or death from any cause in patients with recent ICH and atrial fibrillation (AF). Secondary Aim: To determine if apixaban, compared with aspirin, results in better functional outcomes as measured by the modified Rankin Scale.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age at least 18 years
  • Intracerebral hemorrhage (ICH) (including primary intraventricular hemorrhage) confirmed by brain CT or MRI
  • Can be randomized within 14-120 days after ICH onset
  • Non-valvular AF (defined as atrial fibrillation or atrial flutter), documented by electrocardiography or a physician-confirmed history of prior AF
  • CHA2DS2-VASc score ≥ 2
  • Provision of signed and dated informed consent form by patient or legally authorized representative
  • Able to comply with all study procedures and available for duration of the study
  • For females of reproductive potential: use of highly effective contraception

Exclusion Criteria

  • History of ICH before index event
  • Active infective endocarditis
  • Lobar ICH with cerebral amyloid angiopathy
  • Clear indication for anticoagulant drugs (e.g., requires anticoagulation for deep vein thrombosis or pulmonary embolism) or antiplatelet drugs (e.g., requires aspirin or clopidogrel for recent MI).
  • Previous or planned left atrial appendage closure
  • Clinically significant bleeding diathesis
  • Serum creatinine ≥2.5 mg/dL
  • Active hepatitis or hepatic insufficiency with Child-Pugh score B or C
  • Anemia (hemoglobin <8 g/dL) or thrombocytopenia (<100 x 109/L) that is chronic in the judgment of the investigator
  • Life expectancy <1 year
  • Pregnant or breastfeeding
  • Known allergy to aspirin or apixaban
  • Concomitant participation in a competing therapeutic trial
  • Considered by the investigator to have a condition that precludes safe participation in the trial
  • Unwilling to discontinue prohibited medications

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Apixaban
Apixaban dosing will be 5 mg tablet in morning and 5 mg tablet in evening. A reduced dose of 2.5 mg tablet in morning and 2.5 mg tablet in evening will be used if: (1) ≥2 of the following are present: age ≥80 years, body weight ≤60 kg, or serum creatinine 1.5-2.4 mg/dL, or (2) Patient is taking a strong CYP3A4/pGP inhibitor (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin).
  • Drug: Apixaban
    Apixaban is an oral anticoagulant of the Factor Xa inhibitor class.
    Other names:
    • Eliquis
Placebo Comparator
Aspirin
Aspirin dose will be 81 mg tablet once daily.
  • Drug: Aspirin
    Aspirin is an oral antiplatelet drug.

Recruiting Locations

University of Texas Health Science Center San Antonio
San Antonio, Texas 78229
Contact:
Reza Behrouz, MD

More Details

Status
Recruiting
Sponsor
Yale University

Study Contact

Kevin N Sheth, MD
203-737-8051
kevin.sheth@yale.edu

Detailed Description

ASPIRE is a randomized, double-blinded, phase III clinical trial designed to test the efficacy and safety of anticoagulation, compared with aspirin, in patients with a recent ICH and high-risk non-valvular AF (CHA2DS2-VASc score ≥ 2). Seven hundred patients will be enrolled over 3.5 years and followed for study outcomes for a minimum of 12 months and maximum of 36 months. The primary efficacy outcome is any stroke (hemorrhagic or ischemic) or death from any cause. The secondary efficacy outcome is the change in the modified Rankin Scale score. Recruitment will take place at sites coordinated through the NIH/NINDS StrokeNet.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.