曲克芦丁脑蛋白水解物治疗颅脑创伤的多中心随机对照临床研究

A controlled, multi-center, randomized study of efficacy and safety of troxerutin and cerebroprotein hydrolysate injection for traumatic brain injury

目的探讨曲克芦丁脑蛋白水解物注射液治疗颅脑创伤患者的有效性和安全性。方法前瞻性纳入以卫生计生委北京医院为主的10家医院神经外科2013年6月至2014年7月收治的360例颅脑创伤患者，采用中心分层随机法，将患者分为试验组（240例）与对照组（120例），所有患者均从入院开始用药，试验组给予曲克芦丁脑蛋白水解物注射液（40mg／ml，2ml／d，静脉滴注），对照组给予相同剂量的灭菌注射用水，治疗14d。通过量表比较两组患者的格拉斯哥昏迷评分（GCS）、格拉斯哥预后分级（GOS）、意识恢复情况、语言功能、运动功能、Karnofsky功能状态评分（KPS）及不良事件发生率。结果360例患者中，实际完成321例（治疗组213例，对照组108例）。治疗14d，试验组的平均GCS评分显著高于对照组[分别为（14．1±2．0）分、（13．4±2．3）分，P=0．007]，且试验组清醒患者的比例高于对照组（分别为81．8％、70．0％，P=0．036）。治疗后30d随访，试验组患者的GOS预后良好率（82．3％比58．1％）、语言功能正常百分比（86．1％比61．9％）、上、下肢功能正常的百分比（88．9％、90．4％比78．1％、81．9％）及KPS评分（91．3分比89．1分）均高于对照组（均P〈0．05）。两组均无药物严重不良事件发生。结论曲克芦丁脑蛋白水解物注射液治疗颅脑损伤患者，可缩短患者意识恢复时间，提高患者生命质量和远期预后。

Objective To evaluate the treatment efficacy and safety of troxerutin and cerebroprotein hydrolysate injection（TCHI） in patients with traumatic brain injury. Methods A total of 360 patients with traumatic brain injury were admitted to neurosurgery departments at 10 medical centers （mainly led by Beijing Hospital of Health Ministry） and enrolled into this prospective, multi-center, placebo-controlled, clinical trial from June 2013 to July 2014. Through stratified random sampling, patients were randomized into the TCHI （n =240） group and placebo group （n = 120）. TCHI（40 mg/ml, 2ml/d,iv） or placebo had been intravenously administered for 14 days starting from patient admission. The parameters were compared between the two groups that included Glasgow coma scale （GCS）, Glasgow outcome scale （GOS）, level of consciousness, language and motor functions, Karnofsky performance status scale （KPS） and incidence rate of adverse events. Results The study was successfully conducted in 321 out of the 360 cases, which included 213 patients in the TCHI group and 108 patients in the placebo group. The treatment lasted 14 days in both groups. The GCS in TCHI group （14.1±2.0） was significantly higher than that in placebo group （ 13.4±2.3） （P = 0.007）, and the ratio of consciousness in TCHI group was remarkably higher than that in placebo group （81.8% vs. 70.0% ） （P =0. 036）. At the 30-day follow-up, the rate of good outcomes assessed by GOS （82.3% vs. 58. 1% ）, rate of normal verbal functional （86. 1% vs 61.9% ）, rate of normal function in upper/lower limb （88.9%/90.4% vs. 78. 1%/81.9% ） and KPS score（91.3 vs. 89.1 ） （P 〈 0.05 ）. No serious adverse effects were noted in either group. Conclusion TCHI could be helpful for shortening the coma period and improving the Datient＇s life oualitv as well as long-term outcome.