Shibuya M, Suzuki Y, Sugita K, Saito I, Sasaki T, Takakura K, Nagata I, Kikuchi H, Takemae T, Hidaka H
Department of Neurosurgery, Nagoya University, Japan.
J Neurosurg. 1992 Apr;76(4):571-7. doi: 10.3171/jns.1992.76.4.0571.
With the cooperation of 60 neurosurgical centers in Japan, a prospective randomized placebo-controlled double-blind trial of a new calcium antagonist AT877 (hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, or fasudil hydrochloride) was undertaken to determine the drug's effect on delayed cerebral vasospasm in patients with a ruptured cerebral aneurysm. A total of 276 patients, who underwent surgery within 3 days after subarachnoid hemorrhage (SAH) of Hunt and Hess Grades I to IV, were entered into the study. Nine patients were excluded because of protocol violation. The remaining 267 patients received either 30 mg AT877 or a placebo (saline) by intravenous injection over 30 minutes, three times a day for 14 days following surgery. Demographic and clinical data were well matched between the two groups. It was found that AT877 reduced angiographically demonstrable vasospasm by 38% (from 61% in the placebo group to 38% in the AT877 group, p = 0.0023), low-density regions on computerized tomography associated with vasospasm by 58% (from 38% to 16%, p = 0.0013), and symptomatic vasospasm by 30% (from 50% to 35%, p = 0.0247). Furthermore, AT877 reduced the number of patients with a poor clinical outcome associated with vasospasm (moderate disability or worse on the Glasgow Outcome Scale at 1 month after SAH) by 54% (from 26% to 12%, p = 0.0152). There were no serious adverse events reported in the AT877 group. This is the first report of a placebo-controlled double-blind trial that has demonstrated a significant reduction in angiographically revealed vasospasm by intravenous drug therapy.
在日本60个神经外科中心的合作下，开展了一项前瞻性随机安慰剂对照双盲试验，研究新型钙拮抗剂AT877（六氢-1-(5-异喹啉磺酰基)-1H-1,4-二氮杂卓盐酸盐，即盐酸法舒地尔）对脑动脉瘤破裂患者迟发性脑血管痉挛的影响。共有276例在蛛网膜下腔出血（SAH）后3天内接受手术的Hunt和Hess分级为I至IV级的患者纳入研究。9例患者因违反方案被排除。其余267例患者在术后14天内，每天3次，每次30分钟静脉注射30 mg AT877或安慰剂（生理盐水）。两组的人口统计学和临床数据匹配良好。结果发现，AT877使血管造影显示的血管痉挛减少了38%（从安慰剂组的61%降至AT877组的38%，p = 0.0023），使计算机断层扫描上与血管痉挛相关的低密度区域减少了58%（从38%降至16%，p = 0.0013），使症状性血管痉挛减少了30%（从50%降至35%，p = 0.0247）。此外，AT877使与血管痉挛相关的临床预后不良（SAH后1个月格拉斯哥预后量表评分为中度残疾或更差）的患者数量减少了54%（从26%降至12%，p = 0.0152）。AT877组未报告严重不良事件。这是首次通过安慰剂对照双盲试验证明静脉药物治疗可显著减少血管造影显示的血管痉挛的报告。
