依达拉奉对急性脑梗死治疗时间窗的多中心、双盲、随机对照临床试验

A randomized,double blind,and parallel controlled multicenter clinical trial on therapeutic window of edaravone in acute cerebral infarction

目的观察依达拉奉注射液对急性缺血性脑梗死的有效治疗时间窗。方法采用多中心、随机双盲、安慰剂平行对照临床试验设计方法,共入选224例急性脑梗死患者,进入符合方案分析集209例:试验组(A组)101例(依达拉奉30mg加入氯化钠注射液100mL,iv,gtt,bid×14d),其中起病72h内(A1组)60例,发病72h～1wk内(A2组)41例;对照组(B组)108例(等量氯化钠注射液15mL加入氯化钠注射液100mL,iv,gtt,bid×14d)。2组患者基础治疗相同。治疗前和治疗后d7、14、21对2组患者进行神经功能缺损评分(ESS)和日常生活活动能力(ADL)评分,并进行疗效、安全性比较。结果治疗后d 14 A组和B组ESS有效率(50.5%vs.35.2%),ADL有效率(61.4%vs.43.5%)均有显著差异(P<0.01);d 21 A组和B组ESS有效率(65.4%vs.48.2%),ADL有效率(71.3%vs.55.6%)均有显著差异(P<0.05);其中A1组和A2组d 14有效率(ESS 55%vs.44%、ADL 62%vs.61%)、d 21(ESS 70%vs.58%、ADL 73%vs.68%),均无显著差异(P>0.05)。A组和B组、A1组和A2组不良反应发生率与不良事件发生率均无显著差异(P>0.05)。结论依达拉奉治疗急性缺血性脑梗死有较长的时间窗,发病1wk内使用仍然具有显著的治疗效果。

AIM To study the therapeutic window of edaravone injection on acute cerebral infarction （ACI）. METHODS A multicenter, randomized, placebo-controlled, parallel, double-blind trial was carried out on 224 patients with ACI, of whom 209 patients in per protocol set （PPS） were randomized into trial group （group A, n = 101 ） and control group （group B, n = 108）. The patients in the trial group were divided into two subgroups：A1 group （≤ 72 h, n = 60）and A2 group （72 h-1 wk, n = 41）. Based on conventional treatment, the patients in A1 and A2 group were administered with edaravonc 30 mg twice a day for 14 d, and the patients in control group were administered with same amount of normal saline. Before the treatment and at 7 th, 14 th and 28 th day after the treatment, the neurological deficits and therapeutic effects were assessed by European Stroke Scale （ESS） and Activities of Daily Living （ADL）, respectively. RESULTS At 14 d after the treatment, the effective rates of ESS in group A and B were 50.5% and 35.2% respectively （P 〈 0.01 ）, while those of the ADL were 61.4% and 43.5% respectively （P 〈 0.01）. At 21 d after the treatment, those of ESS in group A and B were 65.4% and 48.2% respectively （P 〈 0.01）, while those of ADL were 71.3% and 55.6% respectively （P 〈 0.05）. There were no significant differences in the adverse events and the adverse reactions between group A and B （P 〉 0.05）. At 14 th and 21 th day after the treatment, there were no significant differences in effective rates between group A1 （14 d： ESS 55%, ADL 62%; 21 d： ESS 70%, ADL 73%） and group A2 （14 d： ESS 44%, ADL 61%; 21 d： ESS 58%, ADL 68%） （P 〉 0.05）. There were no significant differences in the adverse events and the adverse reactions between group A1 and A2 （P 〉 0.05）. CONCLUSION There is a longer therapeutic window of edaravone injection in ACI. Edaravone injection provides effective improvements for both neurological deficits and ADL in ACI （onset within 1 wk） without conspicuous adverse reaction.