Phase 2
N=195
Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation
Ischemic Stroke · Transient Ischemic Attack
Bottom Line
View on ClinicalTrials.gov: NCT02042534 ↗Enrolled (actual)
195
Serious AEs
5.9%
Results posted
Feb 2017
Primary outcome: Primary: Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging — 47; 48 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Rivaroxaban (Drug); Warfarin (Drug)
- Age
- Adult, Older Adult · 19+ yrs
- Sex
- All
- Sponsor
- Asan Medical Center
- Primary completion
- Dec 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging |
47; 48 | — |
| SECONDARY The Number of Patients With Intracranial Bleeding |
30; 25 | 0.6765 |
| SECONDARY The Number of Patients With Recurrent Ischemic Lesion |
28; 31 | 0.3753 |
| SECONDARY Length of Hospitalization |
4.6; 5.6 | <.0001 sig |
| SECONDARY Number of Participants With Modified Rankin Score of 0 or 1 at Week 4 |
79; 64 | 0.3301 |
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.
Eligibility Criteria
Inclusion Criteria: All of below
- Acute ischemic stroke or TIA presumed to be cardioembolic origin (within 5 days from stroke onset) with mild severity: infarct size on DWI less than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere
- Atrial fibrillation including paroxysmal atrial fibrillation: atrial fibrillation must be documented by ECG evidence (e.g., 12-lead ECG, rhythm strip, Holter, pacemaker interrogation) within 30 days before randomization. This could be obtained from a notation in the subject's record (e.g., medical chart, hospital discharge summary).
- Age ≥19 years
- Informed consent
Exclusion Criteria: Any of below
- Chronic renal failure (GFR less than 30ml/min) or severe hepatic impairment
- Significant hemorrhagic transformation (parenchymal hematoma type I or II by the ECASS definition)
- Stroke mechanism of presumed small vessel occlusion: single small subcortical infarct in the perforating artery territory
- Large hemispheric or cerebellar infarction; larger than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere
- Mechanical valve requiring warfarin therapy
- Active internal bleeding
- Prior history of symptomatic intracranial bleeding
: patients with asymptomatic bleedings or microbleedings on MRI are eligible for inclusion
- Major surgery or major trauma within 30 days that might be associated with increased bleeding risk
- Clinically significant gastrointestinal bleeding within 6 months
- Intravenous tissue plasminogen activator use or mechanical embolectomy within 48 hours plus 'significant hemorrhagic transformation as described above (exclusion criteria 2)' or 'large hemispheric infarction or cerebellar infarction as described above (exclusion criteria 4)'
: patients achieving successful reperfusion without hemorrhage nor large infarction are eligible for enrollment
- Severe anemia: hemoglobin 1.7)
- Sustained uncontrolled hypertension: SBP >180 mmHg or DBP >100 mmHg
- Severe devastating illness, such terminal cancer, hepatic failure; therefore, the participants have a life expectancy less than 6 months.
- Planned invasive procedure with potential for uncontrolled bleeding, including major surgery
Data sourced from ClinicalTrials.gov (NCT02042534). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.