Ancrod in acute ischemic stroke: results of 500 subjects beginning treatment within 6 hours of stroke onset in the ancrod stroke program.

Academic Article

Abstract

  • 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). CONCLUSIONS: 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.
  • Authors

    Published In

  • Stroke  Journal
  • Keywords

  • Acute Disease, Aged, Ancrod, Cerebral Hemorrhage, Female, Fibrinolytic Agents, Follow-Up Studies, Humans, Infusions, Intravenous, Male, Middle Aged, Placebos, Stroke, Time Factors, Treatment Failure
  • Digital Object Identifier (doi)

    Author List

  • Levy DE; del Zoppo GJ; Demaerschalk BM; Demchuk AM; Diener H-C; Howard G; Kaste M; Pancioli AM; Ringelstein EB; Spatareanu C
  • Start Page

  • 3796
  • End Page

  • 3803
  • Volume

  • 40
  • Issue

  • 12