Dose escalation of desmoteplase for acute ischemic stroke (DEDAS) - Evidence of safety and efficacy 3 to 9 hours after stroke onset

Background and Purpose-Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke. Methods-DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 mu g/kg and 125 mu g/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined. Results-Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n= 8; 90 mu g/kg: n = 14; 125 mu g/kg: n = 15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 mu g/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 mu g/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 mu g/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 mu g/ kg desmoteplase. In the target population (n = 25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 mu g/kg desmoteplase (P = 0.022). Conclusions-Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 mu g/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).