Results Published From Halted CONSCIOUS-3 Trial of Clazosentan Use in aSAH Patients Undergoing Endovascular Coiling
May 25, 2012—In Stroke, R. Loch Macdonald, MD, et al published findings from the randomized CONSCIOUS-3 trial of clazosentan (Actelion Pharmaceuticals US, Inc., South San Francisco, CA) in patients with aneurysmal subarachnoid hemorrhage (aSAH) undergoing endovascular coiling (2012;43:1462–1469).
The investigators stated that CONSCIOUS-3 was halted prematurely after completion of CONSCIOUS-2, which did not meet its primary endpoint according to a study presentation in February 2011 at the International Stroke Conference.
The purpose of CONSCIOUS-3 was to assess whether clazosentan reduced vasospasm-related morbidity and all-cause mortality after aSAH secured by endovascular coiling. The investigators noted that clazosentan is an endothelin receptor antagonist that has been shown to reduce vasospasm after aSAH.
As summarized in Stroke, this double-blind, placebo-controlled, phase 3 trial randomized patients with aSAH secured by endovascular coiling ≤ 14 days intravenous clazosentan (5 or 15 mg/h) or placebo. The primary composite endpoint (all-cause mortality; vasospasm-related new cerebral infarcts or delayed ischemic neurological deficits; rescue therapy for vasospasm) was evaluated 6 weeks after aSAH. The main secondary endpoint was dichotomized extended Glasgow Outcome Scale at week 12.
In CONSCIOUS-3, 577 of 1,500 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 endpoint occurred in 50 of 189 placebo-treated patients (27%), compared with 47 of 194 patients (24%) treated with clazosentan 5 mg/h (odds ratio [OR], 0.786; 95% CI, 0.479–1.289; P = .34), and 28 of 188 patients (15%) treated with clazosentan 15 mg/h (OR, 0.474; 95% CI, 0.275–0.818; P = .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 = .748), and 28% of patients with clazosentan 15 mg/h (OR, 1.337; 95% CI, 0.802–2.227; P = .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.
From these findings, the investigators concluded that clazosentan 15 mg/h significantly reduced post-aSAH vasospasm-related morbidity/all-cause mortality; however, neither dose improved outcome by extended Glasgow Outcome Scale.
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