Clark W M, Williams B J, Selzer K A, Zweifler R M, Sabounjian L A, Gammans R E
Oregon Stroke Center, Oregon Health Sciences University, Portland 97201, USA.
Stroke. 1999 Dec;30(12):2592-7. doi: 10.1161/01.str.30.12.2592.
BACKGROUND AND PURPOSE: Citicoline (cytidine-5'-diphosphocholine; CDP-choline) may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation. A previous dose-comparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects. METHODS: The current trial was a 33-center, randomized, double-blind, efficacy trial in 394 patients comparing placebo (n=127) with citicoline (n=267) (500 mg po daily) for 6 weeks, with a 6-week posttreatment follow-up period. Patients with acute (24 hours) ischemic strokes clinically assessed to be in the middle cerebral artery territory with National Institutes of Health Stroke Scale (NIHSS) > or = 5 were enrolled. RESULTS: Mean time to treatment was 12 hours, and mean age was 71 for placebo and 70 for citicoline. Although mean baseline NIHSS were similar for both groups, there was a higher percentage of placebo patients with NIHSS <8 (34% vs 22%; P<0.01). The incidence and type of side effects were similar between the groups. The planned primary analysis (logistic regression: 5 categories Barthel) failed the proportional odds assumption and was rendered unreliable. There were no between-group differences seen on the planned secondary assessment analyses at 90 days, including the Barthel Index > or = 95 at 12 weeks (last observation carried forward: placebo 40%; citicoline 40%) or mortality rate (placebo 18%; citicoline 17%). However, post hoc analyses in a subgroup of patients with baseline NIHSS > or = 8 found that citicoline-treated patients were more likely to have a full recovery (Barthel > or = 95): placebo 21%; citicoline 33%; P=0.05; whereas no difference was seen in patients with baseline NIHSS<8 (placebo 77%; citicoline 69%; P>0.1. CONCLUSIONS: The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke who were enrolled in this trial. Post hoc analyses indicate that there may be a subgroup of patients with moderate to severe strokes who would benefit.
背景与目的：胞磷胆碱（胞苷-5'-二磷酸胆碱；CDP-胆碱）可通过稳定细胞膜和减少自由基生成来减轻中枢神经系统缺血性损伤。一项先前针对急性中风患者的剂量比较试验发现，500毫克胞磷胆碱似乎能改善神经功能结局且副作用最小。 方法：本试验是一项在33个中心开展的随机、双盲、疗效试验，纳入394例患者，将安慰剂组（n = 127）与胞磷胆碱组（n = 267）（每日口服500毫克）进行比较，治疗6周，并进行为期6周的治疗后随访。纳入临床评估为大脑中动脉区域急性（24小时）缺血性中风且美国国立卫生研究院卒中量表（NIHSS）评分≥5分的患者。 结果：治疗的平均时间为12小时，安慰剂组的平均年龄为71岁，胞磷胆碱组为70岁。尽管两组的平均基线NIHSS相似，但NIHSS<8分的安慰剂组患者比例更高（34%对22%；P<0.01）。两组间副作用的发生率和类型相似。计划的主要分析（逻辑回归：5类巴氏指数）未满足比例优势假设，结果不可靠。在90天的计划次要评估分析中，包括12周时巴氏指数≥95分（末次观察结转：安慰剂组40%；胞磷胆碱组40%）或死亡率（安慰剂组18%；胞磷胆碱组17%），未发现组间差异。然而，对基线NIHSS≥8分的患者亚组进行的事后分析发现，接受胞磷胆碱治疗的患者更有可能完全康复（巴氏指数≥95分）：安慰剂组21%；胞磷胆碱组33%；P = 0.05；而基线NIHSS<8分的患者未发现差异（安慰剂组77%；胞磷胆碱组69%；P>0.1）。 结论：本研究结果表明，胞磷胆碱在改善本试验中纳入的急性缺血性中风患者的结局方面是安全但无效的。事后分析表明，可能有一组中重度中风患者会从中受益。
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