Background and Purpose
We conducted a randomized exploratory study to assess safety and the probability of a favorable outcome with adjunctive argatroban, a direct thrombin-inhibitor, administered to rt-PA treated ischemic stroke patients.
Methods
Patients treated with standard-dose rt-PA, not receiving endovascular therapy, were randomized to receive no argatroban or argatroban (100-μg/kg bolus) followed by infusion of either 1 μg/kg/min (low-dose) or 3 μg/kg/min (high-dose) for 48 hours. Safety was incidence of symptomatic intracerebral hemorrhage (sICH). Probability of clinical benefit (mRS 0–1 at 90-days) was estimated using a conservative Bayesian Poisson model (neutral prior probability centered at relative risk [RR]=1.0 and 95% prior intervals: 0.33–3.0).
Results
Ninety patients were randomized: 29 to rt-PA alone, 30 to rt-PA + low-dose argatroban, and 31 to rt-PA + high-dose argatroban. Rates of sICH were similar among control, low-dose and high-dose arms: 3/29 (10%); 4/30 (13%); and 2/31 (7%), respectively. At 90-days 6 (21%) rt-PA alone; 9 (30%) low-dose, and 10 (32%) high-dose patients were mRS 0–1. The RR (95% Credible Interval) for mRS 0–1 with low, high, and either low or high dose argatroban was 1.17 (0.57, 2.37), 1.27 (0.63, 2.53), and 1.34 (0.68, 2.76). The probability that adjunctive argatroban was superior to rt-PA alone was 67%, 74%, and 79% for low, high, and low or high dose, respectively.
Conclusions
In patients treated with rt-PA, adjunctive argatroban was not associated with increased risk of sICH and provides evidence that a definitive effectiveness trial is indicated.