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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)
- Publication Year :
- 2011
-
Abstract
- Summary 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.
- Subjects :
- Relative risk reduction
Male
medicine.medical_specialty
Endothelin A Receptor Antagonists
Pyridines
medicine.medical_treatment
Medizin
Glasgow Outcome Scale
Tetrazoles
610 Medicine & health
Placebo
law.invention
Dioxanes
10180 Clinic for Neurosurgery
Randomized controlled trial
Double-Blind Method
law
medicine
Clinical endpoint
Humans
Vasospasm, Intracranial
cardiovascular diseases
Endovascular coiling
Sulfonamides
Dose-Response Relationship, Drug
business.industry
Endothelin receptor antagonist
Vasospasm
Subarachnoid Hemorrhage
medicine.disease
Surgical Instruments
Surgery
Pyrimidines
Treatment Outcome
2728 Neurology (clinical)
Anesthesia
Female
Neurology (clinical)
10023 Institute of Intensive Care Medicine
business
Subjects
Details
- Language :
- English
- ISSN :
- 00558311
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....1168797fda9a68b08623b99f36bf00e1