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Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling

Macdonald, R Loch; Higashida, Randall T; Keller, Emanuela; Mayer, Stephan A; Molyneux, Andy; Raabe, Andreas; Vajkoczy, Peter; Wanke, Isabel; Bach, Doris; Frey, Aline; Nowbakht, Pegah; Roux, Sébastien; Kassell, Neal (2012). Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke, 43(6):1463-1469.

Abstract

BACKGROUND AND PURPOSE: Clazosentan, an endothelin receptor antagonist, has been shown to reduce vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). CONSCIOUS-3 assessed whether clazosentan reduced vasospasm-related morbidity and all-cause mortality postaSAH secured by endovascular coiling.

METHODS: This double-blind, placebo-controlled, phase III trial randomized patients with aSAH secured by endovascular coiling to ≤ 14 days intravenous clazosentan (5 or 15 mg/h) or placebo. The primary composite end point (all-cause mortality; vasospasm-related new cerebral infarcts or delayed ischemic neurological deficits; rescue therapy for vasospasm) was evaluated 6 weeks postaSAH. The main secondary end point was dichotomized extended Glasgow Outcome Scale (week 12).

RESULTS: CONSCIOUS-3 was halted prematurely following completion of CONSCIOUS-2; 577/1500 of planned patients (38%) were enrolled and 571 were treated (placebo, n=189; clazosentan 5 mg/h, n=194; clazosentan 15 mg/h, n=188). The primary end point occurred in 50/189 of placebo-treated patients (27%), compared with 47/194 patients (24%) treated with clazosentan 5 mg/h (odds ratio [OR], 0.786; 95% CI, 0.479-1.289; P=0.340), and 28/188 patients (15%) treated with clazosentan 15 mg/h (OR, 0.474; 95% CI, 0.275-0.818; P=0.007). Poor outcome (extended Glasgow Outcome Scale score ≤ 4) occurred in 24% of patients with placebo, 25% of patients with clazosentan 5 mg/h (OR, 0.918; 95% CI, 0.546-1.544; P=0.748), and 28% of patients with clazosentan 15 mg/h (OR, 1.337; 95% CI, 0.802-2.227; P=0.266). Pulmonary complications, anemia, and hypotension were more common in patients who received clazosentan than in those who received placebo. At week 12, mortality was 6%, 4%, and 6% with placebo, clazosentan 5 mg/h, and clazosentan 15 mg/h, respectively.

CONCLUSIONS: Clazosentan 15 mg/h significantly reduced postaSAH vasospasm-related morbidity/all-cause mortality; however, neither dose improved outcome (extended Glasgow Outcome Scale).

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Intensive Care Medicine
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Neurology (clinical)
Health Sciences > Cardiology and Cardiovascular Medicine
Health Sciences > Advanced and Specialized Nursing
Language:English
Date:June 2012
Deposited On:23 Nov 2020 16:00
Last Modified:24 Oct 2024 01:37
Publisher:American Heart Association
ISSN:0039-2499
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1161/STROKEAHA.111.648980
PubMed ID:22403047

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