Table 1.

Summary of clinical data regarding ET-1 antagonists in managing cerebral vasospasm.

Authors/year of publication	Type of study	Number of patients	Results of the study
Macdonald et al. (2008) [71] (CONSCIOUS-1)	Randomized, double-blind, placebo-controlled phase-II dose-finding trial	413 patients	Reduction of vasospasm in a dose-dependent fashion from 66% in the placebo group to 23% in the 15 mg/h clazosentan group (risk reduction, 65%; 95% CI, 47% to 78%; P < 0.0001) Clazosentan was associated with pulmonary complications, hypotension, and anemia
Macdonald et al. (2011) [74] (CONSCIOUS-2)	Randomised, double-blind, placebo-controlled phase-III trial	Clazosentan group (5 mg/h, n = 768 patients) and placebo group (n = 389 patients)	The primary endpoint was met in 161 patients (21%) of the clazosentan group and in 97 patients (25%) of the placebo group. Relative risk reduction 17%, (95% CI −4 to 33; P = 0.10). Poor functional outcome (GOSE score ≤ 4) occurred in 224 (29%) in the clazosentan group and in 95 patients (25%) in the placebo group. Mortality was 6% in both groups. Clazosentan was associated with lung complications, anaemia, and hypotension
Macdonald et al. (2012) [76] (CONSCIOUS-3)	Randomized, double-blind, placebo-controlled, phase-III trial	CONSCIOUS-3 was halted prematurely following the completion of the CONSCIOUS-2. A total of 577/1500 of planned patients were enrolled, and 571 were treated (placebo, n = 189 patients; clazosentan 5 mg/h, n = 194 patients; clazosentan 15 mg/h, n = 188 patients).	The primary endpoint was reached in 50/189 of placebo-treated patients (27%), compared with 47/194 patients (24%) treated with clazosentan 5 mg/h and 28/188 patients (15%) treated with clazosentan 15 mg/h. Poor outcome (extended Glasgow Outcome Scale score ≤ 4) occurred in 24% of patients in the placebo group, 25% of patients with clazosentan 5 mg/h, and 28% of patients with clazosentan 15 mg/h. Mortality was 6%, 4%, and 6% with placebo, clazosentan 5 mg/h, and clazosentan 15 mg/h, respectively. Clazosentan-associated complications were pulmonary complications, anemia, and hypotension