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

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: David E Levy, Gregory J del Zoppo, Bart M Demaerschalk, Andrew M Demchuk, Hans-Christoph Diener, George Howard, Markku Kaste, Arthur M Pancioli, E Bernd Ringelstein, Carmen Spatareanu, Warren W Wasiewski
• Journal: Stroke (Stroke) Vol. 40 Issue 12 Pg. 3796-803 (Dec 2009) ISSN: 1524-4628 [Electronic] United States
• PMID: 19875736 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinolytic Agents
• Placebos
• Ancrod

Topics

• Acute Disease
• Aged
• Ancrod (administration & dosage, adverse effects)
• Cerebral Hemorrhage (chemically induced)
• Female
• Fibrinolytic Agents (administration & dosage, adverse effects)
• Follow-Up Studies
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Placebos
• Stroke (drug therapy)
• Time Factors
• Treatment Failure