[同时使用脑蛋白水解物和阿替普酶对脑卒中患者脑梗死出血转化及功能转归的影响：CEREHETIS，一项随机、多中心的前瞻性试验]

[Effects of simultaneous use of Cerebrolysin and alteplase on hemorrhagic transformation of brain infarction and functional outcome in stroke patients: CEREHETIS, a randomized, multicenter pilot trial].

作者信息

Khasanova D R, Kalinin M N

机构信息

Kazan State Medical University, Kazan, Russia.

Interregional Clinical Diagnostic Center, Kazan, Russia.

出版信息

Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(8. Vyp. 2):60-69. doi: 10.17116/jnevro202312308260.

DOI:10.17116/jnevro202312308260

PMID:37682097

Abstract

OBJECTIVE

The study aimed to assess effects of the simultaneous use of Cerebrolysin and intravenous thrombolysis (Alteplase) on hemorrhagic transformation (HT) and functional outcome as well as to analyze the treatment safety in acute stroke patients.

MATERIAL AND METHODS

It was a prospective, randomized, open-label, multicenter, parallel-group, active-controlled pilot study (Trial Registration Number: ISRCTN87656744, https://doi.org/10.1186/ISRCTN87656744, Trial registration date: 16/02/2021). The intervention group (=126) was treated with Cerebrolysin infusion (30 mL) started simultaneously with Alteplase (0.9 mg/kg) via a separate IV line. The Cerebrolysin treatment continued for 14 consecutive days with the baseline therapy along. The control group (=215) received only Alteplase and the baseline therapy. The primary endpoints were the rate of any and symptomatic hemorrhagic transformation (HT) from admission to day 14. Secondary endpoints were treatment safety and functional outcome measured with the National Institutes of Health stroke scale (NIHSS) in 24 h and on day 14, and with the modified Rankin scale (mRS) on day 90.

RESULTS

Treatment with Cerebrolysin resulted in a significant reduction of the symptomatic HT rate with an odds ratio of 0.248 (95% CI: 0.072-0.851; =0.019). No serious adverse events related to Cerebrolysin were observed. On day 14, the intervention group showed a significant reduction in the NIHSS score (=0.045). However, no difference in the mRS score was observed on day 90, but there was a trend towards its improvement.

CONCLUSION

The combination of Cerebrolysin and Alteplase was safe and significantly reduced the rate of symptomatic HT and improved early neurological deficit. However, no difference in functional outcome was found on day 90, but there was a trend towards favorable functional outcome.

摘要

目的

本研究旨在评估同时使用脑蛋白水解物和静脉溶栓（阿替普酶）对出血性转化（HT）和功能结局的影响，并分析急性卒中患者的治疗安全性。

材料与方法

这是一项前瞻性、随机、开放标签、多中心、平行组、活性对照的试点研究（试验注册号：ISRCTN87656744，https://doi.org/10.1186/ISRCTN87656744，试验注册日期：2021年2月16日）。干预组（n = 126）在通过单独静脉通路开始阿替普酶（0.9 mg/kg）治疗的同时，静脉输注脑蛋白水解物（30 mL）。脑蛋白水解物治疗与基础治疗一起持续14天。对照组（n = 215）仅接受阿替普酶和基础治疗。主要终点是从入院到第14天任何类型和有症状的出血性转化（HT）发生率。次要终点是治疗安全性以及在24小时和第14天使用美国国立卫生研究院卒中量表（NIHSS）测量的功能结局，以及在第90天使用改良Rankin量表（mRS）测量的功能结局。

结果

使用脑蛋白水解物治疗可使有症状的HT发生率显著降低，优势比为0.248（95%CI：0.072 - 0.851；P = 0.019）。未观察到与脑蛋白水解物相关的严重不良事件。在第14天，干预组的NIHSS评分显著降低（P = 0.045）。然而，在第90天，mRS评分未观察到差异，但有改善的趋势。