Macdonald R Loch, Higashida Randall T, Keller Emanuela, Mayer Stephan A, Molyneux Andy, Raabe Andreas, Vajkoczy Peter, Wanke Isabel, Bach Doris, Frey Aline, Marr Angelina, Roux Sébastien, Kassell Neal
St. Michael's Hospital, Toronto, ON, Canada.
Acta Neurochir Suppl. 2013;115:27-31. doi: 10.1007/978-3-7091-1192-5_7.
We report here results of a randomized, double-blind, placebo-controlled study ( http://www.ClinicalTrials.gov , NCT00558311) that investigated the effect of clazosentan (5 mg/h, n = 768) or placebo (n = 389) administered for up to 14 days in patients with aneurysmal subarachnoid hemorrhage (SAH) repaired by surgical clipping. The primary endpoint was a composite of all-cause mortality, new cerebral infarction or delayed ischemic neurological deficit due to vasospasm, and rescue therapy for vasospasm. The main secondary endpoint was the Glasgow Outcome Scale Extended (GOSE), which was dichotomized. Twenty-one percent of clazosentan- compared to 25% of placebo-treated patients met the primary endpoint (relative risk reduction [RRR] [95% CI]: 17% [-4% to 33%]; p = 0.10). Poor outcome (GOSE score ≤ 4) occurred in 29% of clazosentan- and 25% of placebo-treated patients (RRR: -18% [-45% to 4%]; p = 0.10). In prespecified subgroups, mortality/vasospasm-related morbidity was reduced in clazosentan-treated patients by 33% (8-51%) in poor WFNS (World Federation of Neurological Surgeons) grade (≥III) and 25% (5-41%) in patients with diffuse, thick SAH. Lung complications, anemia and hypotension occurred more frequently with clazosentan. Mortality (week 12) was 6% in both groups. The results showed that clazosentan nonsignificantly decreased mortality/vasospasm-related morbidity and nonsignificantly increased poor functional outcome in patients with aneurysmal SAH undergoing surgical clipping.
我们在此报告一项随机、双盲、安慰剂对照研究（http://www.ClinicalTrials.gov，NCT00558311）的结果，该研究调查了在接受手术夹闭修复的动脉瘤性蛛网膜下腔出血（SAH）患者中，连续14天给予氯沙坦（5毫克/小时，n = 768）或安慰剂（n = 389）的效果。主要终点是全因死亡率、因血管痉挛导致的新发脑梗死或延迟性缺血性神经功能缺损以及血管痉挛的抢救治疗的综合指标。主要次要终点是二分法的扩展格拉斯哥预后量表（GOSE）。氯沙坦治疗的患者中有21%达到主要终点，而安慰剂治疗的患者中有25%达到主要终点（相对风险降低[RRR][95%CI]：17%[-4%至33%]；p = 0.10）。氯沙坦治疗的患者中有29%出现不良结局（GOSE评分≤4），安慰剂治疗的患者中有25%出现不良结局（RRR：-18%[-45%至4%]；p = 0.10）。在预先设定的亚组中，氯沙坦治疗的患者中，世界神经外科医师联合会（WFNS）分级较差（≥III级）者的死亡率/血管痉挛相关发病率降低了33%（8%-51%），弥漫性、厚SAH患者降低了25%（5%-41%）。氯沙坦治疗组肺部并发症、贫血和低血压的发生率更高。两组的死亡率（第12周）均为6%。结果表明，氯沙坦在接受手术夹闭的动脉瘤性SAH患者中，对降低死亡率/血管痉挛相关发病率无显著作用，对增加不良功能结局也无显著作用。
