Division of Neurosurgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Neurol Sci. 2020 Feb;41(2):281-293. doi: 10.1007/s10072-019-04053-5. Epub 2019 Sep 7.
To evaluate the safety and efficacy of Cerebrolysin as an add-on therapy to local standard treatment protocol in patients after moderate-to-severe traumatic brain injury.
The patients received the study medication in addition to standard care (50 mL of Cerebrolysin or physiological saline solution daily for 10 days, followed by two additional treatment cycles with 10 mL daily for 10 days) in a prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-centre phase IIIb/IV trial. The primary endpoint was a multidimensional ensemble of 14 outcome scales pooled to be analyzed by means of the multivariate, correlation-sensitive Wei-Lachin procedure.
In 46 enrolled TBI patients (Cerebrolysin 22, placebo 24), three single outcomes showed stand-alone statistically significant superiority of Cerebrolysin [Stroop Word/Dots Interference (p = 0.0415, Mann-Whitney(MW) = 0.6816, 95% CI 0.51-0.86); Color Trails Tests 1 and 2 (p = 0.0223/0.0170, MW = 0.72/0.73, 95% CI 0.53-0.90/0.54-0.91), both effect sizes lying above the benchmark for "large" superiority (MW > 0.71)]. While for the primary multivariate ensemble, statistical significance was just missed in the intention-to-treat population (p < 0.1, MW = 0.63, 95% CI 0.48-0.77, derived standardized mean difference (SMD) 0.45, 95% CI -0.07 to 1.04, derived OR 2.1, 95% CI 0.89-5.95), the per-protocol analysis showed a statistical significant superiority of Cerebrolysin (p = 0.0240, MW = 0.69, 95% CI 0.53 to 0.85, derived SMD 0.69, 95% CI 0.09 to 1.47, derived OR 3.2, 95% CI 1.16 to 12.8), with effect sizes of six single outcomes lying above the benchmark for "large" superiority. Safety aspects were comparable to placebo.
Our trial suggests beneficial effects of Cerebrolysin on outcome after TBI. Results should be confirmed by a larger RCT with a comparable multidimensional approach.
评估脑活素作为附加治疗药物用于中重度创伤性脑损伤患者的安全性和疗效。
在一项前瞻性、随机、双盲、安慰剂对照、平行组、多中心 IIIb/IV 期试验中，患者在接受标准治疗（每天 50ml 脑活素或生理盐水，连续 10 天，随后再进行两个 10 天的 10ml 每日治疗周期）的同时接受研究药物治疗。主要终点是通过多元相关敏感 Wei-Lachin 程序分析的 14 项综合结果量表的多维综合指标。
在纳入的 46 例 TBI 患者（脑活素 22 例，安慰剂 24 例）中，3 项单一结果显示脑活素具有统计学显著优势[Stroop 字/点干扰（p=0.0415，MW=0.6816，95%CI 0.51-0.86）；色迹试验 1 和 2（p=0.0223/0.0170，MW=0.72/0.73，95%CI 0.53-0.90/0.54-0.91），两个效应大小均大于“大”优势的基准值（MW>0.71）]。虽然对于主要的多变量综合指标，意向治疗人群的统计学意义仅差一点（p<0.1，MW=0.63，95%CI 0.48-0.77，衍生标准化均数差（SMD）0.45，95%CI-0.07 至 1.04，衍生 OR 2.1，95%CI 0.89-5.95），但方案分析显示脑活素具有统计学显著优势（p=0.0240，MW=0.69，95%CI 0.53-0.85，衍生 SMD 0.69，95%CI 0.09-1.47，衍生 OR 3.2，95%CI 1.16-12.8），6 项单一结果的效应大小均大于“大”优势的基准值。安全性方面与安慰剂相当。
我们的试验提示脑活素对 TBI 后的结局有有益影响。结果应通过具有类似多维方法的更大 RCT 来证实。
