TY - JOUR
T1 - Ancrod in acute ischemic stroke
T2 - Results of 500 subjects beginning treatment within 6 hours of stroke onset in the ancrod stroke program
AU - Levy, David E.
AU - Del Zoppo, Gregory J.
AU - Demaerschalk, Bart M.
AU - Demchuk, Andrew M.
AU - Diener, Hans Christoph
AU - Howard, George
AU - Kaste, Markku
AU - Pancioli, Arthur M.
AU - Spatareanu, Carmen
AU - Wasiewski, Warren W.
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - Ancrod
KW - Anticoagulant
KW - Cerebral infarction
KW - Defibrinogenation
KW - Fibrinogen
KW - Fibrinolytic agent
KW - Recovery of function
KW - Therapeutics
KW - Treatment outcome
UR - http://www.scopus.com/inward/record.url?scp=73449128279&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73449128279&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.109.565119
DO - 10.1161/STROKEAHA.109.565119
M3 - Article
C2 - 19875736
AN - SCOPUS:73449128279
SN - 0039-2499
VL - 40
SP - 3796
EP - 3803
JO - Stroke
JF - Stroke
IS - 12
ER -