Lees K R, Asplund K, Carolei A, Davis S M, Diener H C, Kaste M, Orgogozo J M, Whitehead J
University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, UK.
Lancet. 2000 Jun 3;355(9219):1949-54. doi: 10.1016/s0140-6736(00)02326-6.
Early treatment may improve acute ischaemic stroke outcome. Gavestinel is a selective antagonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor, and is neuroprotective in animal models of ischaemic stroke.
We did a randomised, double-blind, placebo-controlled trial to test whether gavestinel could improve functional outcome after acute stroke in human beings. Conscious patients with stroke involving limb weakness received either gavestinel at an intravenous loading dose of 800 mg followed by 200 mg every 12 h for five doses, or matching placebo, within 6 h of stroke onset. Stratification variables were age and stroke severity. A computed tomography brain scan within 18 h of stroke onset identified the primary efficacy population with ischaemic stroke. Outcome was assessed by an independent observer with the Barthel index at 3 months. Three outcome categories were applied: good (Barthel index 95-100), moderate (60-90), and poor (0-55 or dead). Analysis was by intention to treat.
Of 1804 patients randomised, 16 received no treatment, and 333 had primary intracranial haemorrhage. 891 patients received gavestinel and 897 received placebo. Outcome in 721 patients who received gavestinel and were analysed for the primary endpoint at 3 months was good in 246 (34.1%), moderate in 136 (18.8%), and poor in 339 (47.0%), compared with 256 (34.9%), 133 (18.1%), and 345 (47.0%), respectively, of 734 patients who received placebo (p=0.8). Mortality at 3 months was 147 (20.4%) in the gavestinel group and 138 (18.8%) in the placebo group. Outcomes within preplanned subgroup and secondary analyses were also neutral. There were no significant differences in serious side-effects between the groups.
Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome.
早期治疗可能改善急性缺血性卒中的预后。加维斯替奈是N-甲基-D-天冬氨酸（NMDA）受体甘氨酸位点的选择性拮抗剂，在缺血性卒中动物模型中具有神经保护作用。
我们进行了一项随机、双盲、安慰剂对照试验，以测试加维斯替奈能否改善人类急性卒中后的功能预后。意识清醒且有肢体无力症状的卒中患者在卒中发作6小时内，要么接受静脉负荷剂量800mg的加维斯替奈，随后每12小时200mg，共五剂，要么接受匹配的安慰剂。分层变量为年龄和卒中严重程度。卒中发作18小时内的脑部计算机断层扫描确定了缺血性卒中的主要疗效人群。3个月时由独立观察者用巴氏指数评估预后。应用了三个预后类别：良好（巴氏指数95 - 100）、中等（60 - 90）和差（0 - 55或死亡）。分析采用意向性治疗。
在1804例随机分组的患者中，16例未接受治疗，333例有原发性颅内出血。891例患者接受加维斯替奈治疗，897例接受安慰剂治疗。721例接受加维斯替奈治疗并在3个月时进行主要终点分析的患者中，预后良好的有246例（34.1%），中等的有136例（18.8%），差的有339例（47.0%）；而734例接受安慰剂治疗的患者中，相应比例分别为256例（34.9%）、133例（18.1%）和345例（47.0%）（p = 0.8）。加维斯替奈组3个月时的死亡率为147例（20.4%），安慰剂组为138例（18.8%）。预先计划的亚组分析和次要分析中的结果也均为阴性。两组之间严重副作用无显著差异。
急性缺血性卒中6小时内使用加维斯替奈治疗并未改善预后。
