Alter M
Jefferson Health System, Lankenau Hospital, Wynnewood, Pennsylvania 19096, USA.
Ann N Y Acad Sci. 1998 Jun 19;845:391-401. doi: 10.1111/j.1749-6632.1998.tb09691.x.
GM1 ganglioside decreases the severity of ischemic brain lesions in experimental models, although the mechanism is uncertain. In clinical trials involving patients with stroke, efficacy has been reported in some but not in others. However, some of the latter also showed efficacy after analyses not planned before the trial began. Analyses of the trials done to date revealed design differences sufficiently large so as to preclude meta-analysis of the results. Moreover, flaws in these studies may account for some of their failure to demonstrate that GM1 therapy is efficacious in ischemic stroke. Several of these flaws are discussed, including small sample size; attrition of the study cohort; inclusion of stroke severity and type that made demonstrations of a beneficial effect difficult; use of inappropriate clinical and outcome measuring instruments; delay in enrollment; inappropriate statistical analyses; inadequate dose; inappropriate route of administration; a too short duration of treatment. Improvements in these design features in future clinical trials of GM1 may yet demonstrate efficacy of this drug in acute ischemic stroke.
GM1神经节苷脂可减轻实验模型中缺血性脑损伤的严重程度，但其机制尚不清楚。在涉及中风患者的临床试验中，有些报道了其疗效，而有些则没有。然而，后者中的一些在试验开始前未计划的分析后也显示出疗效。对迄今为止所做试验的分析表明，设计差异足够大，以至于无法对结果进行荟萃分析。此外，这些研究中的缺陷可能是它们未能证明GM1治疗对缺血性中风有效的部分原因。本文讨论了其中的几个缺陷，包括样本量小；研究队列的损耗；纳入了使有益效果难以证明的中风严重程度和类型；使用了不适当的临床和结果测量工具；入组延迟；不适当的统计分析；剂量不足；给药途径不当；治疗持续时间过短。GM1未来临床试验中这些设计特征的改进可能会证明该药物对急性缺血性中风的疗效。
