Clinical trial NCT02042534
Conditions: Ischemic Stroke Transient Ischemic Attack
Keywords: stroke TIA
Sponsor: Asan Medical Center
Start date: 2014-01-01; Completion date: 2015-12-01
Enrollment: 195 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Rationale Acute ischemic stroke due to atrial fibrillation (AF) carries a high risk for early recurrence. In acute stage, guidelines recommend aspirin, but do not recommend anticoagulation due to the increased risk of intracranial bleeding. Since, aspirin has a limited efficacy of preventing recurrent stroke in AF, expert consensus suggests early anticoagulation in non-severe stroke with AF. The current practice for acute ischemic stroke patients with AF is delayed warfarin administration with aspirin use for non-minor stroke or immediate warfarin administration (sometimes with heparin bridging) for minor stroke. However, conventional anticoagulation with warfarin in acute ischemic stroke with AF has the following limitations: 1) risk of intracranial bleeding particularly in acute stage, 2) delayed action and transient paradoxical thrombogenic tendency due to the inhibition of protein C, resulting in the risk of early recurrent embolic stroke, and 3) prolongation of hospitalization waiting for full anticoagulation. In contrast, as compared to warfarin, rivaroxaban is advantageous for reduced risk of intracranial bleeding and immediate anticoagulation efficacy.

Goal The current trial will examine whether early initiation (within 5 days from stroke onset) of rivaroxaban as compared to conventional warfarin would reduce intracranial bleeding, recurrent embolic stroke, and hospital stay in patients with acute ischemic stroke due to AF.

Detailed description:
Primary endpoint: Composite of MRI-defined intracranial bleeding and recurrent ischemic lesion within 1 month after randomization (rivaroxaban vs conventional warfarin)

Arms: arm 1: Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days. arm 2: Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 \[2.0 - 3.0\].
Interventions: intervention 1: Rivaroxaban intervention 2: Warfarin
Intervention descriptions: intervention 1: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min.

The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety. intervention 2: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.

Protocol documents: