Department of Neurology, Hospital St. John of God, Vienna, Austria.
Int J Stroke. 2013 Feb;8(2):95-104. doi: 10.1111/j.1747-4949.2012.00901.x. Epub 2012 Sep 26.
The neurotrophic drug Cerebrolysin accelerated recovery and prevented acute neuronal damage in preclinical models of ischaemia. Previous clinical trials support therapeutic effects in stroke patients. The study investigated whether the combination with alteplase and Cerebrolysin is safe and can further reduce disability after acute ischaemic stroke.
This placebo-controlled, double-blind trial involved 119 patients with acute ischaemic hemispheric stroke, randomly assigned to a combined treatment with alteplase plus Cerebrolysin or placebo (administered 1 h after thrombolytic treatment) starting within three-hours after onset of symptoms. A daily i.v. infusion of 30 ml Cerebrolysin or placebo was given for 10 consecutive days. Primary outcome was the modified Rankin Scale at day 90. A sequential design with interim analyses was applied.
The third interim analysis did not show a benefit in the modified Rankin Scale for Cerebrolysin on day 90 compared to placebo and the study was stopped. The National Institutes of Health Stroke Scale responder analysis (secondary outcome measure) showed significantly more patients with an improvement of 6 or more points (or a total score of 0 or 1) after two-, five-, 10, and 30 days in the Cerebrolysin group. Similar trends were observed for the modified Rankin Scale responder analysis without achieving statistical significance. There was no difference between treatment groups regarding adverse events.
The combination of Cerebrolysin with recombinant tissue-Plasminogen Activator is safe for treatment of acute ischaemic stroke but did not improve outcome at day 90. During the treatment period with Cerebrolysin (10 days), significantly more patients had a favourable response in neurological outcome measures (National Institutes of Health Stroke Scale) as compared to the placebo group.
神经营养药物 Cerebrolysin 可加速临床前模型缺血性损伤的恢复并预防急性神经元损伤。先前的临床试验支持该药物对中风患者的治疗作用。本研究旨在探讨 Cerebrolysin 联合阿替普酶治疗是否安全，并进一步降低急性缺血性中风患者的残疾程度。
本安慰剂对照、双盲试验纳入 119 例急性缺血性大脑半球中风患者，随机分为阿替普酶联合 Cerebrolysin 治疗组或安慰剂组（溶栓治疗后 1 小时内开始使用），两组患者均在症状发作后 3 小时内开始治疗。Cerebrolysin 或安慰剂（每天 30ml，静脉输注，连续 10 天）治疗组。主要结局指标为 90 天改良 Rankin 量表评分。采用序贯设计和中期分析。
第三次中期分析显示，与安慰剂相比，Cerebrolysin 治疗组 90 天改良 Rankin 量表评分无获益，因此停止了该研究。国立卫生研究院卒中量表应答分析（次要结局指标）显示，在第 2、5、10 和 30 天，Cerebrolysin 组有更多患者的评分改善 6 分或以上（或总分为 0 或 1）。改良 Rankin 量表应答分析也观察到了相似的趋势，但未达到统计学意义。两组患者不良事件发生率无差异。
Cerebrolysin 联合重组组织型纤溶酶原激活剂治疗急性缺血性脑卒中安全，但不能改善 90 天的结局。在 Cerebrolysin 治疗期间（10 天），与安慰剂组相比，更多患者在神经功能结局（国立卫生研究院卒中量表）方面有良好的应答。
