A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: A cooperative study in North America
A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: A cooperative study in North America
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DOI：
10.3171/jns.1997.86.3.0467
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发表时间：
1997-03-01
影响因子：
4.1
通讯作者：
Alves, WM
中科院分区：
文献类型：
--
作者：
Haley, EC;Kassell, NF;Alves, WM
为了测试甲磺酸替拉扎德（一种非糖皮质激素21-氨基类固醇）在改善蛛网膜下腔出血（SAH）患者预后方面的安全性和有效性，在北美54个神经外科中心进行了一项前瞻性随机、双盲、溶剂对照试验，纳入了902例患者。5例患者在接受任何研究药物前被排除。在897名接受至少一剂研究药物的患者中，300名接受含有柠檬酸盐载体的安慰剂，298名接受每天2 mg/kg的替拉扎德，299名接受每天6 mg/kg的替拉扎德，所有患者均在SAH后48小时内开始静脉给药，并持续至出血后10天。所有患者均口服尼莫地平治疗。在SAH后3个月，两组在死亡率、格拉斯哥结局量表的良好结局或就业状况方面没有显著差异（p < 0.025）。在SAH后的前14天内，两组间临床症状性或血管造影可识别的脑血管痉挛的发生率或严重程度无显著差异。入院时按性别和神经学分级分层的死亡率数据（根据修改的世界神经外科医生联盟量表评估）表明，IV至V级的男性在媒介物组中具有33%的死亡率，在2 mg/kg/天替拉扎德组中具有52%的死亡率（D = 0.29），在6 mg/kg/天替拉扎德组中具有5%的死亡率（p = 0.03）。在本试验中，SAH后给予甲磺酸替瑞拉扎达6 mg/kg/d，持续8 - 10天，并不能改善蛛网膜下腔出血患者的总体预后。在本试验中，替拉扎德的疗效与先前在欧洲、澳大利亚和新西兰报告的试验（其中替拉扎德剂量水平为6 mg/kg/天降低了死亡率并增加了良好恢复）的差异可能是由于患者入院特征的差异和/或管理方案的差异，包括抗惊厥药物的使用。
To test the safety and efficacy of tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, in improving the outcome of patients with aneurysmal subarachnoid hemorrhage (SAH), 902 patients were enrolled in a prospective randomized, double-blind, vehicle-controlled trial at 54 North American neurosurgical centers. Five patients were excluded prior to receiving any study drug. Of 897 patients who received at least one dose of study medication, 300 received a placebo containing a citrate vehicle, 298 received 2 mg/kg per day tirilazad, and 299 received 6 mg/kg per day tirilazad, all administered intravenously beginning within 48 hours of the SAH and continuing through 10 days posthemorrhage. All patients were also treated with orally administered nimodipine. At 3 months post-SAH, there were no significant differences (p < 0.025) among the groups with regard to mortality rate, favorable outcome on the Glasgow Outcome Scale, or employment status. During the first 14 days after the SAH, there were no significant differences among the groups in the incidence or severity of clinically symptomatic or angiographically identifiable cerebral vasospasm. Mortality data stratified by gender and neurological grade on admission (assessed according to a modified World Federation of Neurological Surgeons scale) demonstrated that the men with Grades lV to V had a 33% mortal ily rate in the vehicle group, 52% in the 2 mg/kg per day tirilazad group (D = 0.29), and 5% in the 6 mg/kg per day tirilazad group (p = 0.03). Tirilazad was well tolerated at both dose levels.Tirilazad mesylate at dosage levels of up to 6 mg/kg per day for 8 to 10 days following SAH did not improve the overall outcome in patients with aneurysmal SAH in this trial. The differences in the efficacy of tirilazad in this trial and a previously reported trial in Europe, Australia, and New Zealand, in which dosage levels of tirilazad of 6 mg/kg per day reduced mortality rates and increased good recovery, may be a result of differences in admission characteristics of the patients and/or differences in management protocols, including the use of anticonvulsant medications.