Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Lancet. 2012 Jul 28;380(9839):349-57. doi: 10.1016/S0140-6736(12)60813-7. Epub 2012 Jun 11.
BACKGROUND: Citicoline is approved in some countries for the treatment of acute ischaemic stroke. The drug has shown some evidence of efficacy in a pooled analysis. We sought to confirm the efficacy of citicoline in a larger trial. METHODS: We undertook a randomised, placebo-controlled, sequential trial in patients with moderate-to-severe acute ischaemic stroke admitted at university hospitals in Germany, Portugal, and Spain. Using a centralised minimisation process, patients were randomly assigned in a 1:1 ratio to receive citicoline or placebo within 24 h after the onset of symptoms (1000 mg every 12 h intravenously during the first 3 days and orally thereafter for a total of 6 weeks [2×500 mg oral tablets given every 12 h]). All study participants were masked. The primary outcome was recovery at 90 days measured by a global test combining three measures of success: National Institutes of Health Stroke Scale ≤1, modified Rankin score ≤1, and Barthel Index ≥95. Safety endpoints included symptomatic intracranial haemorrhage in patients treated with recombinant tissue plasminogen activator, neurological deterioration, and mortality. This trial is registered, NCT00331890. RESULTS: 2298 patients were enrolled into the study from Nov 26, 2006, to Oct 27, 2011. 37 centres in Spain, 11 in Portugal, and 11 in Germany recruited patients. Of the 2298 patients who gave informed consent and underwent randomisation, 1148 were assigned to citicoline and 1150 to placebo. The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients. The final randomised analysis was based on data for 2298 patients: 1148 in citicoline group and 1150 in placebo group. Global recovery was similar in both groups (odds ratio 1·03, 95% CI 0·86-1·25; p=0·364). No significant differences were reported in the safety variables nor in the rate of adverse events. INTERPRETATION: Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke. FUNDING: Ferrer Grupo.
背景：胞磷胆碱在一些国家被批准用于治疗急性缺血性脑卒中。该药在汇总分析中显示出一定的疗效证据。我们旨在更大规模的试验中确认胞磷胆碱的疗效。
方法：我们在德国、葡萄牙和西班牙的大学附属医院开展了一项随机、安慰剂对照、序贯试验。通过中央化最小化程序，患者在症状发作后 24 小时内按 1:1 比例随机分配接受胞磷胆碱或安慰剂治疗（前 3 天内每 12 小时静脉注射 1000mg，此后口服共 6 周[每天 2 次，每次 500mg 口服片剂]）。所有研究参与者均设盲。主要结局是通过综合三种成功测量指标的全球评分在 90 天时的恢复情况：国立卫生研究院卒中量表（NIHSS）评分≤1、改良 Rankin 量表评分≤1 和巴氏指数（Barthel Index）≥95。安全性终点包括接受重组组织型纤溶酶原激活剂治疗的患者的症状性颅内出血、神经功能恶化和死亡率。本试验已注册，NCT00331890。
结果：2006 年 11 月 26 日至 2011 年 10 月 27 日，共纳入 2298 例患者。来自西班牙的 37 个中心、葡萄牙的 11 个中心和德国的 11 个中心纳入了患者。2298 例患者在知情同意并随机分组后，1148 例被分配至胞磷胆碱组，1150 例被分配至安慰剂组。根据 2078 例患者的完整数据，在第三次中期分析时，因无效而停止试验。最终随机分析基于 2298 例患者的数据：胞磷胆碱组 1148 例，安慰剂组 1150 例。两组的总体恢复情况相似（比值比 1.03，95%CI 0.86-1.25；p=0.364）。在安全性变量或不良事件发生率方面均无显著差异。
解释：在 ICTUS 试验的情况下，胞磷胆碱对治疗中度至重度急性缺血性脑卒中无效。
资金来源：Ferrer 集团。
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