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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-50634

Macdonald, R L; Higashida, R T; Keller, E; Mayer, S A; Molyneux, A; Raabe, A; Vajkoczy, P; Wanke, I; Bach, D; Frey, A; Marr, A; Roux, S; Kassell, N (2011). Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurology, 10(7):618-625.

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Clazosentan, an endothelin receptor antagonist, significantly and dose-dependently reduced angiographic vasospasm after aneurysmal subarachnoid haemorrhage (aSAH). We investigated whether clazosentan reduced vasospasm-related morbidity and all-cause mortality.

In this randomised, double-blind, placebo-controlled, phase 3 study, we randomly assigned patients with aSAH secured by surgical clipping to clazosentan (5 mg/h, n=768) or placebo (n=389) for up to 14 days (27 countries, 102 sites, inpatient and outpatient settings) using an interactive web response system. The primary composite endpoint (week 6) included all-cause mortality, vasospasm-related new cerebral infarcts, delayed ischaemic neurological deficit due to vasospasm, and rescue therapy for vasospasm. The main secondary endpoint was dichotomised extended Glasgow outcome scale (GOSE; week 12). This trial is registered with ClinicalTrials.gov, number NCT00558311.

In the all-treated dataset, the primary endpoint was met in 161 (21%) of 764 clazosentan-treated patients and 97 (25%) of 383 placebo-treated patients (relative risk reduction 17%, 95% CI -4 to 33; p=0·10). Poor functional outcome (GOSE score ≤4) occurred in 224 (29%) clazosentan-treated patients and 95 (25%) placebo-treated patients (-18%, -45 to 4; p=0·10). Lung complications, anaemia, and hypotension were more common with clazosentan. Mortality (week 12) was 6% in both groups.

Clazosentan at 5 mg/h had no significant effect on mortality and vasospasm-related morbidity or functional outcome. Further investigation of patients undergoing endovascular coiling of ruptured aneurysms is needed to fully understand the potential usefulness of clazosentan in patients with aSAH.

Actelion Pharmaceuticals.

Copyright © 2011 Elsevier Ltd. All rights reserved.


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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurosurgery
Dewey Decimal Classification:610 Medicine & health
Date:June 2011
Deposited On:26 Feb 2012 09:08
Last Modified:08 Dec 2013 09:30
Additional Information:Comment in: Lancet Neurol. 2011 Oct;10(10):871; author reply 871-2. - Lancet Neurol. 2011 Jul;10(7):593-595.
Publisher DOI:10.1016/S1474-4422(11)70108-9
Official URL:http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2811%2970108-9/fulltext
PubMed ID:21640651

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