Effects of a hydroxyl radical scavenger on delayed ischemic neurological deficits following aneurysmal subarachnoid hemorrhage: Results of a multicenter, placebo-controlled double-blind trial
Effects of a hydroxyl radical scavenger on delayed ischemic neurological deficits following aneurysmal subarachnoid hemorrhage: Results of a multicenter, placebo-controlled double-blind trial
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DOI：
10.3171/jns.1996.84.5.0792
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发表时间：
1996-05-01
影响因子：
4.1
通讯作者：
Sasaki, T
中科院分区：
文献类型：
--
作者：
Asano, T;Takakura, K;Sasaki, T
AVS((+/-)-N，N‘-亚丙二氨基烟酰胺；Nicaraven)是一种水溶性的新型合成化合物，在中性pH的水环境条件下没有明显的血管活性，但可以清除羟基自由基。根据以往的实验和临床研究结果显示，AVS对脑血管痉挛和缺血性脑损伤有明显的改善作用，采用多中心、安慰剂对照的双盲临床试验，以验证其对血管痉挛所致的迟发性缺血性神经功能障碍(DIND)和蛛网膜下腔出血(SAH)患者的总体预后的有利作用。共有162名入院时格拉斯哥昏迷评分在7到15之间的SAH患者参加了试验。SAH后5d内开始给药(安慰剂为AVS 4g或葡萄糖4g，静脉滴注6~8h，1次/d)，持续给药10~14d。对这些患者的意向治疗分析表明，DINDS的总发生率显著降低了34.5%(安慰剂54.2%，AVS 35.5%；p<；0.05，Mann-Whitney U-test)。治疗后1个月格拉斯哥预后量表(GOS)评分明显改善(P<；0.05，U检验)。在3个月时，两组间的GOS评分差异在U检验中逐渐缩小(P<；0.10)，但好结果的百分比有增加的趋势，相对增加了20.3%(AVS 76.3%，安慰剂63.4%；P<；0.10，卡方检验)，累积死亡率显著降低(P<；0.05，对数等级检验)。未观察到与治疗有关的明显不良反应。AVS在SAH治疗中的有效性由以下事实强烈表明：该药显著改善了DINDS，导致1个月时GOS评分显著改善，并将累积死亡率降低3个月。
A water-soluble, novel synthetic compound, AVS ((+/-)-N,N'-propylenedinicotinamide; nicaraven) has no demonstrable vasoactive properties but scavenges hydroxyl radicals in aqueous environmental conditions at neutral pH. Based on the results of preceding experimental and clinical studies showing marked ameliorative effects of AVS on cerebral vasospasm and ischemic brain damage, a multicenter, placebo-controlled double-blind clinical trial was undertaken to verify its beneficial effects on delayed ischemic neurological deficits (DINDs) due to vasospasm and on the overall outcome of patients with subarachnoid hemorrhage (SAH). A total of 162 patients with SAH who had Glasgow Coma Scale scores between 7 and 15 on admission were enrolled in the trial. Drug administration (4 g AVS or 4 g glucose as placebo; infused intravenously for 6-8 hours once a day) was begun within 5 days post-SAH and continued for 10 to 14 days. Intent-to-treat analysis of these patients revealed that the overall incidence of DINDs, which was defined as an exacerbation of impaired consciousness and/or focal neurological deficits, was significantly reduced, by 34.5% (placebo 54.2%, AVS 35.5%; p < 0.05, Mann-Whitney U-test). The Glasgow Outcome Scale (GOS) score at I month was significantly improved by AVS (P < 0.05, U-test). At 3 months, the difference in the GOS scores between the groups became marginal on U-tests (p < 0.10), but the percentage of good outcome tended to increase, with a relative increase of 20.3% (AVS 76.3%, placebo 63.4%; p < 0.10, chi-square test), and the cumulative incidence of death was significantly reduced (p < 0.05, log-rank test). No significant adverse reaction attributable to treatment was observed. The usefulness of AVS in therapy for SAH is strongly indicated by the fact that the agent significantly ameliorated DINDs, leading to a marked improvement in the GOS scores at 1 month, as well as a reduction in the cumulative incidence of death by 3 months.