Remote Ischemic Conditioning After Stroke Trial 2: A Phase IIb Randomized Controlled Trial in Hyperacute Stroke
Remote Ischemic Conditioning After Stroke Trial 2: A Phase IIb Randomized Controlled Trial in Hyperacute Stroke
复制标题
DOI：
10.1161/jaha.119.013572
复制
发表时间：
2019-12-03
影响因子：
5.4
通讯作者：
Bath, Philip M.
中科院分区：
文献类型：
--
作者：
England, Timothy J.;Hedstrom, Amanda;Bath, Philip M.
背景肢体缺血和再灌注（远程缺血调节 [RIC]）的反复发作可以保护大脑免受缺血性再灌注损伤。方法和结果我们对超急性卒中患者进行了一项 IIb 期盲法剂量递增假对照试验，随机以 1:1 的比例接受 RIC（四个 5 分钟周期）或对非麻痹性上肢进行假手术，分 3 组增加剂量，在 6 小时内开始。发作。主要结果是试验可行性（招募、人员流失）。次要结局包括依从性、耐受性、安全性（严重不良事件）、第 1 天和第 4 天的血浆生物标志物（S100-ss 蛋白、基质金属蛋白酶-9 和神经元特异性烯醇化酶）和功能结果。从 2 个中心招募了 60 名参与者（每月 3 名），没有失访：随机分组时间为 4 小时 5 分钟（SD 72 分钟），年龄 72 岁 (12)，男性 60%，血压 154/80 mm Hg (25/12)，美国国立卫生研究院卒中量表 8.4 (6.9)，55% 接受溶栓治疗。 RIC 耐受性良好，RIC 和假手术之间的依从性没有差异，由于出院或转移，两组在第 3 天均出现下降（P=0.001，重复测量方差分析）。假手术组的 S100ss 增加（平均增加 111 pg/mL [302]，P=0.041，重复测量 ANCOVA），但 RIC 组则没有。基质金属蛋白酶-9、神经元特异性烯醇化酶、严重不良事件的数量（RIC 10 与假手术 10，P=0.81）、死亡（2 与 4，P=0.36）或改良 Rankin 量表评分（2 [四分位距 1-4]、2 [四分位距，1-3]；P=0.85）均无差异。结论 RIC 在超急性卒中中是可行的每天两次，持续 2 天，对于少数患有超急性中风的人群来说似乎是安全的。有必要进行更大规模的 III 期试验。
BackgroundRepeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may protect the brain from ischemic reperfusion injury.Methods and ResultsWe performed a phase IIb blinded dose-escalation sham-controlled trial in patients with hyperacute stroke, randomized 1:1 to receive RIC (four 5-minute cycles) or sham to the nonparetic upper limb, in 3 blocks of increasing dose, starting within 6 hours of ictus. The primary outcome was trial feasibility (recruitment, attrition). Secondary outcomes included adherence, tolerability, safety (serious adverse events), plasma biomarkers at days 1 and 4 (S100-ss protein, matrix metalloproteinase-9, and neuron-specific enolase), and functional outcome. Sixty participants were recruited from 2 centers (3 per month) with no loss to follow-up: time to randomization 4 hours 5 minutes (SD 72 minutes), age 72 years (12), men 60%, blood pressure 154/80 mm Hg (25/12), National Institutes of Health Stroke Scale 8.4 (6.9), and 55% thrombolyzed. RIC was well tolerated with adherence not differing between RIC and sham, falling in both groups on day 3 (P=0.001, repeated measures ANOVA) because of discharge or transfer. S100ss increased in the sham group (mean rise 111 pg/mL [302], P=0.041, repeated measures ANCOVA) but not the RIC group. There were no differences in matrix metalloproteinase-9, neuron-specific enolase, number with serious adverse events (RIC 10 versus sham 10, P=0.81), deaths (2 versus 4, P=0.36), or modified Rankin Scale score (2 [interquartile range 1-4], 2 [interquartile range, 1-3]; P=0.85).ConclusionsRIC in hyperacute stroke is feasible when given twice daily for 2 days and appears safe in a small population with hyperacute stroke. A larger phase III trial is warranted.