PHASE-II TRIAL OF TIRILAZAD IN ANEURYSMAL SUBARACHNOID HEMORRHAGE - A REPORT OF THE COOPERATIVE ANEURYSM STUDY
PHASE-II TRIAL OF TIRILAZAD IN ANEURYSMAL SUBARACHNOID HEMORRHAGE - A REPORT OF THE COOPERATIVE ANEURYSM STUDY
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DOI：
10.3171/jns.1995.82.5.0786
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发表时间：
1995-05-01
影响因子：
4.1
通讯作者：
HANSEN, CA
中科院分区：
文献类型：
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作者：
HALEY, EC;KASSELL, NF;HANSEN, CA
甲磺酸替拉扎德是一种21-氨基类固醇自由基清除剂，在蛛网膜下腔出血（SAH）和局灶性脑缺血的动物模型中，已被证明可改善脑血管痉挛并减少梗死面积。在准备进行大规模的临床试验中，在12个加拿大神经外科中心进行的随机、双盲、溶剂对照、序贯剂量递增研究中，对不同剂量的替拉扎德的安全性进行了测试。245例血管造影证实的蛛网膜下腔出血患者在出血后72小时内连续入组研究。患者被分配到三个剂量等级之一：每天静脉注射0.6 mg/kg、2 mg/kg或6 mg/kg替拉扎德或溶媒，分次给药，直至SAH后第10天。Ah患者也接受口服尼莫地平。尽管对肝脏和心脏毒性进行了密切监测，但在三种剂量中的任何一种剂量下都没有发现替拉扎德治疗的严重副作用。与溶媒治疗组的结果相比，在2 mg/kg/天替拉唑治疗组中观察到总体3个月患者结果改善的趋势。我们得出结论，甲磺酸替拉扎德在SAH患者中的安全剂量高达6 mg/kg/天，长达10天，是一种很有前途的药物治疗蛛网膜下腔出血患者。
Tirilazad mesylate, a 21-aminosteroid free-radical scavenger, has been shown to ameliorate cerebral vasospasm and reduce infarct size in animal models of subarachnoid hemorrhage (SAH) and focal cerebral ischemia. In preparation for performing large-scale clinical trials in humans with aneurysmal SAH, the safety of varying doses of tirilazad was tested in a randomized, double-blind, vehicle-controlled, sequential dose-escalation study at 12 Canadian neurosurgical centers. Two hundred forty-five patients with an aneurysmal SAH documented by angiography were enrolled in the study sequentially within 72 hours of hemorrhage. The patients were assigned to one of three dosage tiers: receiving 0.6 mg/kg, 2 mg/kg, or 6 mg/kg tirilazad or vehicle per day intravenously in divided doses through Day 10 following the SAH. Ah patients also received oral nimodipine. No serious side effects of tirilazad treatment were identified at any of the three doses, despite close monitoring of hepatic and cardiac toxicity. A trend toward improvement in overall 3-month patient outcome was seen in the 2 mg/kg per day tirilazad-treated group compared to the outcomes in the vehicle-treated groups. We conclude that tirilazad mesylate is safe in SAH patients at doses up to 6 mg/kg per day for up to 10 days and is a promising drug for the treatment of patients with aneurysmal SAH.