In:
Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. 6 ( 2012-06), p. 1463-1469
Abstract:
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). Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT00940095.
Type of Medium:
Online Resource
ISSN:
0039-2499
,
1524-4628
DOI:
10.1161/STROKEAHA.111.648980
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2012
detail.hit.zdb_id:
1467823-8
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