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.
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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)
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Chemical References |
- Fibrinolytic Agents
- Placebos
- Ancrod
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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
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