To compare the safety and functional outcomes of high-dose unfractionated heparin (UH) with those of aspirin in patients with nonlacunar ischemic stroke.
- Heparin (acute stroke) Drug
Intervention Desc: Intravenous anticoagulant.
Multicenter, multinational, randomized, open-label, parallel-group trial.
Prior to enrollment, all patients must undergo a brain CT, a full medical history and physical exam, documentation of vital signs, blood tests, resting 12-lead EKG, an evaluation of concomitant therapy, NIHSS scoring, and, if available, carotid Doppler sonography and echocardiography. Eligible patients will be randomized to receive either aspirin or intravenous UH. Patients in the UH group will receive an initial bolus of 40 IU/kg, followed by an infusion of 12 IU/kg/hr. Locally calibrated activated partial thromboplastin time (aPTT) ratios will be used to titrate the infusion to a therapeutic UH level of 0.3 - 0.5 IU/mL. aPTT ratios will be recorded every 6 hours until two consecutive results indicate a therapeutic UH level, and every 12 hours thereafter. Patients in the aspirin group will receive 160-325 mg/day (with the recommended dose being 300 mg/day) either orally or via nasogastric tube. The first aspirin dose may be intravenous. Both aspirin and UH regimens will be continued for 5 - 7 days.
All patients will have their vital signs monitored every 8 hours and their NIHSS score evaluated every 24 hours for 7 days, or until discharge. A follow-up CT will be performed upon discontinuation of the study medication. NIHSS and MRS scores will be assessed blindly at 90 days.
|Type||Measure||Time Frame||Safety Issue|
|Primary||Functional outcome at 90 days, defined by a dichotomized MRS score, where a score of 0 - 2 constitutes a favorable outcome, and a score of 3 - 6 constitutes an unfavorable outcome.|
|Secondary||Trichotomized NIHSS score at 7 days, where an 'improved' outcome is either a score of 0 or at least 4 points less than the baseline score, an 'unchanged' outcome is within 3 points of the baseline score, and a 'worsened' outcome is either death or a score at least 4 points greater than baseline; proportion of baseline-adjusted NIHSS scores =< 1 at 90 days; single and combined incidence of recurrent ischemic stroke, recurrent ischemic stroke associated with nonvalvular atrial fibrillation, deep venous thrombosis, acute myocardial infarction, pulmonary embolism and death within 1 day of treatment; symptomatic intracerebral bleeding or systemic bleeding requiring transfusion within 1 day of treatment; thrombocytopenia, defined as a platelet count < 100,000/mm3 or a 40% decrease from baseline values, within 1 day of treatment; all mortality at 90 days.|