Randomized trial of argatroban plus recombinant tissue-type plasminogen activator for acute ischemic stroke (ARAIS): Rationale and design

Background Previous studies have implied the efficacy and safety of argatroban plus recombinant tissue-type plasminogen activator (r-tPA) in patients with acute ischemic stroke. Further trials are needed to establish convincing conclusions in a large sample size. Research design and methods Argatroban plus r-tPA for Acute Ischemic Stroke (ARAIS) trial is a multicenter, prospective, randomized, open-label, and blind-end point trial. The trial proposes to randomize 808 patients with acute ischemic stroke National Institutes of Health Stroke Scale (NIHSS score >= 6 at the time of randomization) within 4.5 hours of symptom onset to receive argatroban (100 mu g/kg bolus followed by an infusion of 1.0 mu g/kg per minute for 48 hours) plus r-tPA or r-tPA alone. The primary end point is the proportion of patients with an excellent outcome of no clinically significant residual stroke deficits (modified Rankin scale 0-1) at 90 days. Secondary end points include the proportion of patients with a good outcome (modified Rankin scale 0-2) at 90 days, early neurological improvement (NIHSS score >= 2-point decrease) at 48 hours, early neurological deterioration (NIHSS score >= 4-point increase) at 48 hours, decrease in the NIHSS score from baseline to 14 days, and stroke recurrence or other vascular events at 90 days. Safety end points include symptomatic intracerebral hemorrhage, parenchymal hematoma type 2, and major systemic bleeding. Conclusion ARAIS trial will evaluate whether argatroban plus r-tPA is superior to r-tPA alone in improving functional outcomes in acute ischemic stroke patients in a large sample population.