Ancrod in acute ischemic stroke: Results of 500 subjects beginning treatment within 6 hours of stroke onset in the ancrod stroke program Journal Article
| Authors: | Levy, D. E.; Del Zoppo, G. J.; Demaerschalk, B. M.; Demchuk, A. M.; Diener, H. C.; Howard, G.; Kaste, M.; Pancioli, A. M.; Spatareanu, C.; Wasiewski, W. W. |
| Article Title: | 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. © 2009 American Heart Association. All rights reserved. |
| Keywords: | controlled study; treatment outcome; aged; middle aged; treatment failure; recovery of function; major clinical study; clinical trial; constipation; mortality; placebo; drug efficacy; drug safety; follow-up studies; controlled clinical trial; bleeding; nausea; randomized controlled trial; vomiting; kidney failure; hematuria; time factors; fever; pneumonia; lung embolism; acute kidney failure; hypokalemia; hypotension; insomnia; depression; acetylsalicylic acid; heart infarction; multicenter study; stroke; urinary tract infection; transient ischemic attack; headache; double blind procedure; infusions, intravenous; heart atrium fibrillation; brain hemorrhage; congestive heart failure; ancrod; anticoagulant; cerebral infarction; defibrinogenation; fibrinogen; fibrinolytic agent; therapeutics; antithrombocytic agent; aspiration pneumonia; brain edema; brain hernia; bronchitis; cerebrovascular accident; fibrinogen blood level; national institutes of health stroke scale; parallel design; rankin scale; upper respiratory tract infection; acute disease; cerebral hemorrhage; fibrinolytic agents; placebos |
| Journal Title: | Stroke |
| Volume: | 40 |
| Issue: | 12 |
| ISSN: | 0039-2499 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2009-12-01 |
| Start Page: | 3796 |
| End Page: | 3803 |
| Language: | English |
| DOI: | 10.1161/strokeaha.109.565119 |
| PUBMED: | 19875736 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "CODEN: SJCCA" - "Source: Scopus" |
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