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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BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Actelion Pharmaceuticals. Copyright © 2011 Elsevier Ltd. All rights reserved.
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|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|
|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.|
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