Ancrod in Acute Ischemic Stroke Results of 500 Subjects Beginning Treatment Within 6 Hours of Stroke Onset in the Ancrod Stroke Program

Background and Purpose-Previous studies of multiple-day dosing with the defibrinogenating agent, ancrod, in acute ischemic stroke yielded conflicting results but suggested that a brief dosing regimen might improve efficacy and safety. The Ancrod Stroke Program was designed to test this concept in subjects beginning ancrod or placebo within 6 hours of the onset of acute ischemic stroke. Methods-Five hundred subjects with acute ischemic stroke who could begin receiving study material within 6 hours of symptom onset were infused intravenously with either ancrod (0.167 IU/kg per hour) or placebo over 2 or 3 hours. The primary efficacy outcome was a dichotomized, modified Rankin score at 90 days with less stringent cut-points for higher prestroke modified Rankin score and pretreatment NIHSS total score ("responder analysis"). Safety variables included mortality, major bleeding, and intracranial hemorrhage. Results-Although the desired changes in fibrinogen level were seen in >90% of ancrod subjects, interim analysis for futility led to the study being halted for lack of efficacy. Positive responder status in the interim dataset was seen in 39.6% of ancrod subjects and 37.2% of placebo subjects (P = 0.47). Ninety-day mortality did not differ between the 2 groups (ancrod, 15.6%; placebo, 14.1%; P = 0.32), and the incidence of symptomatic intracranial hemorrhage within the first 72 hours, although not significantly different in ancrod compared to placebo subjects (P = 0.19), was approximately twice as high (3.9% vs 2.0%; P = 0.19). Conclusion-These results demonstrate that intravenous ancrod starting within 6 hours after symptom onset in a broad selection of subjects with ischemic stroke did not improve their outcome and revealed a trend to increased bleeding despite successful efforts to achieve rapid initial defibrinogenation and avoid prolonged hypofibrinogenemia. (Stroke. 2009; 40: 3796-3803.)