Desmoteplase 3 to 9 Hours after Major Artery Occlusion Stroke

Rüdiger Von Kummer; Etsuro Mori; Thomas Truelsen; Jens Kristian S. Jensen; Bjørn A. Grønning; Jochen B. Fiebach; Karl Olof Lovblad; Salvador Pedraza; Javier M. Romero; Hugues Chabriat; Ku Chou Chang; Antoni Dávalos; Gary A. Ford; James Grotta; Markku Kaste; Lee H. Schwamm; Ashfaq Shuaib; Gregory W. Albers

doi:10.1161/STROKEAHA.116.013715

Desmoteplase 3 to 9 Hours after Major Artery Occlusion Stroke

Rüdiger Von Kummer, Etsuro Mori, Thomas Truelsen, Jens Kristian S. Jensen, Bjørn A. Grønning, Jochen B. Fiebach, Karl Olof Lovblad, Salvador Pedraza, Javier M. Romero, Hugues Chabriat, Ku Chou Chang, Antoni Dávalos, Gary A. Ford, James Grotta, Markku Kaste, Lee H. Schwamm, Ashfaq Shuaib, Gregory W. Albers

Department of Medicine

Research output: Contribution to journal › Article › Research › peer-review

39 Citations (Scopus)

Abstract

© 2016 American Heart Association, Inc. Background and Purpose - The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window. Methods - Ischemic stroke patients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 μg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events. Results - In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08-2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0-2) at day 90 in both the treatment arms. Conclusions - Late treatment with intravenous 90 μg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661.

Original language	English
Pages (from-to)	2880-2887
Journal	Stroke
Volume	47
Issue number	12
DOIs	https://doi.org/10.1161/STROKEAHA.116.013715
Publication status	Published - 1 Dec 2016

Keywords

brain ischemia
cerebral arteries
goals
intracranial hemorrhage
stroke

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10.1161/STROKEAHA.116.013715

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Von Kummer, R., Mori, E., Truelsen, T., Jensen, J. K. S., Grønning, B. A., Fiebach, J. B., Lovblad, K. O., Pedraza, S., Romero, J. M., Chabriat, H., Chang, K. C., Dávalos, A., Ford, G. A., Grotta, J., Kaste, M., Schwamm, L. H., Shuaib, A., & Albers, G. W. (2016). Desmoteplase 3 to 9 Hours after Major Artery Occlusion Stroke. Stroke, 47(12), 2880-2887. https://doi.org/10.1161/STROKEAHA.116.013715

@article{577d51cf8db543398768c8015d39bab0,

title = "Desmoteplase 3 to 9 Hours after Major Artery Occlusion Stroke",

abstract = "{\textcopyright} 2016 American Heart Association, Inc. Background and Purpose - The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window. Methods - Ischemic stroke patients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 μg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events. Results - In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08-2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0-2) at day 90 in both the treatment arms. Conclusions - Late treatment with intravenous 90 μg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661.",

keywords = "brain ischemia, cerebral arteries, goals, intracranial hemorrhage, stroke",

author = "{Von Kummer}, R{\"u}diger and Etsuro Mori and Thomas Truelsen and Jensen, {Jens Kristian S.} and Gr{\o}nning, {Bj{\o}rn A.} and Fiebach, {Jochen B.} and Lovblad, {Karl Olof} and Salvador Pedraza and Romero, {Javier M.} and Hugues Chabriat and Chang, {Ku Chou} and Antoni D{\'a}valos and Ford, {Gary A.} and James Grotta and Markku Kaste and Schwamm, {Lee H.} and Ashfaq Shuaib and Albers, {Gregory W.}",

year = "2016",

month = dec,

day = "1",

doi = "10.1161/STROKEAHA.116.013715",

language = "English",

volume = "47",

pages = "2880--2887",

number = "12",

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Von Kummer, R, Mori, E, Truelsen, T, Jensen, JKS, Grønning, BA, Fiebach, JB, Lovblad, KO, Pedraza, S, Romero, JM, Chabriat, H, Chang, KC, Dávalos, A, Ford, GA, Grotta, J, Kaste, M, Schwamm, LH, Shuaib, A & Albers, GW 2016, 'Desmoteplase 3 to 9 Hours after Major Artery Occlusion Stroke', Stroke, vol. 47, no. 12, pp. 2880-2887. https://doi.org/10.1161/STROKEAHA.116.013715

TY - JOUR

T1 - Desmoteplase 3 to 9 Hours after Major Artery Occlusion Stroke

AU - Von Kummer, Rüdiger

AU - Mori, Etsuro

AU - Truelsen, Thomas

AU - Jensen, Jens Kristian S.

AU - Grønning, Bjørn A.

AU - Fiebach, Jochen B.

AU - Lovblad, Karl Olof

AU - Pedraza, Salvador

AU - Romero, Javier M.

AU - Chabriat, Hugues

AU - Chang, Ku Chou

AU - Dávalos, Antoni

AU - Ford, Gary A.

AU - Grotta, James

AU - Kaste, Markku

AU - Schwamm, Lee H.

AU - Shuaib, Ashfaq

AU - Albers, Gregory W.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - © 2016 American Heart Association, Inc. Background and Purpose - The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window. Methods - Ischemic stroke patients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 μg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events. Results - In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08-2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0-2) at day 90 in both the treatment arms. Conclusions - Late treatment with intravenous 90 μg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661.

AB - © 2016 American Heart Association, Inc. Background and Purpose - The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window. Methods - Ischemic stroke patients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 μg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events. Results - In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08-2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0-2) at day 90 in both the treatment arms. Conclusions - Late treatment with intravenous 90 μg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661.

KW - brain ischemia

KW - cerebral arteries

KW - goals

KW - intracranial hemorrhage

KW - stroke

U2 - 10.1161/STROKEAHA.116.013715

DO - 10.1161/STROKEAHA.116.013715

M3 - Article

VL - 47

SP - 2880

EP - 2887

IS - 12

ER -

Desmoteplase 3 to 9 Hours after Major Artery Occlusion Stroke

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Keywords

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