负荷剂量氯吡格雷治疗非心源性急性脑梗死／短暂性脑缺血发作的预研究

A Pilot Trial of Clopidogrel of Loading Dosage to Treat non Cardiaoembolic Acute Ischemic Stroke /Transient Ischemic Attack in China(CLASS-CHINA Pilot).

目的初步评价负荷剂量氯吡格雷治疗非心源性急性脑梗死/短暂性脑缺血发作(transient ischemic attack,TIA)的可行性和安全性。方法前瞻性、多中心、随机对照、平行开放研究。起病48 h内入院的非心源性急性脑梗死/TIA患者,随机分为负荷剂量氯吡格雷组(首剂300 mg,之后75 mg·d-1)、标准剂量氯吡格雷组(75 mg·d-1),连用28 d。主要疗效指标:7 d内卒中进展或复发;主要安全指标:危及生命出血。结果3个研究中心共收集71例患者。与常规剂量组相比,负荷剂量氯吡格雷组7 d内卒中进展或复发相对危险度下降(RRR)55.8%(95%CI:-14.2%～82.9%),3个月时死亡或依赖RRR 35.2%(95%CI:-39.2%～69.8%),4周时有效率、3个月时良好预后率均显示负荷剂量组优于常规剂量组的优势。但所有比较均未达到统计学差异。结论:负荷剂量氯吡格雷治疗非心源性急性脑梗死/TIA有优于常规剂量氯吡格雷的趋势,未发现安全问题,值得进一步研究。

Objective To explore the feasibility and safety of loading dose of clopidogrel treatment in patients with non cardiaoembolic acute ischemic stroke / transient ischemic attack （TIA）. Methods A multicenter, prospective, randomized, controlled parallel clinical trial was conducted to evaluate the feasibility and safety. Patients with non cardiaoembolic ischemic stroke or TIA within 48 h were randomized into load dose （300mg followed by daily 75 mg） or standard dose （daily 75 mg） elopidogrel group, respectively, and followed up for 90 days. Primary outcome was progressive or recurrent stroke within 7 d. Second outcomes included dead or dependent （ modified Rankin Scale, mRS 〉 2） , favorable outcome （ mRS 0 - 1 or Barthel Index 95 - 100） at 90 d and efficacy （ NIHSS improvement t〉18% ） at 28 d. Life threatening bleeding was used as primary safety endpoint. Results From July 2005 to March 2006, a total of 71 patients from 3 centers were enrolled and completed follow-up. Compared with non-loading dose treatment, loading clopidogrel treatment had a relative risk reduction （RRR） of 55.8% （95% CI ： - 14. 2 - 82.9%, P = 0. 077 ） for progressive or recurrent rate within 7 d, 35.2% （95% CI： -39. 2 - 69. 8% , P =0. 259） for death or dependence at 90 d. The efficacy at 28 d and the favorable outcome at 90 d were slightly better in patients treated with loading dosage clopidogrel （ P 〉 0. 05 ）. No life-threatening bleeding was found in all patients and no difference in safety of this drug was found between the two groups. Compared with the data from 3 randomized double blind clinical trials with aspirin, a favorable trend was suggested in loading dose clopidogrel treatment. Conclusions The load dose clopidogrel seems to be safe and effective in treating non cardioembolic acute ischemic stroke/TIA, which merits further study.