Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke-Full Dose Regimen Stroke Trial
Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke-Full Dose Regimen Stroke Trial
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DOI：
10.1161/strokeaha.115.010260
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发表时间：
2015-09-01
期刊：
影响因子：
8.3
通讯作者：
Pancioli, Arthur M.
中科院分区：
文献类型：
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作者：
Adeoye, Opeolu;Sucharew, Heidi;Pancioli, Arthur M.
背景和目的 - 在急性缺血性中风 (AIS) 和 CLEAR 增强方案 (CLEAR-ER) 试验中使用依替巴肽和重组组织型纤溶酶原激活剂 (r-tPA; CLEAR) 进行裂解的联合方法证明，与单独使用 r-tPA 相比，减少剂量的 r-tPA 加糖蛋白 2b/3a 抑制剂依替巴肽在 AIS 中的安全性。 CLEAR-全剂量方案 (CLEAR-FDR) 试验的目的是评估接受全剂量 r-tPA 加依替巴肽联合治疗的 AIS 患者中症状性脑出血 (sICH) 的发生率。方法-CLEAR-FDR 是一项单臂、前瞻性、开放标签、多中心研究。年龄为 18 至 85 岁的患者在症状出现 3 小时内接受 0.9 mg/kg IV r-tPA 治疗。获得同意后，给予依替巴肽（135μg/kg推注并以每分钟0.75μg/kg输注2小时）。主要终点是 36 小时内经历 sICH 的患者比例。由独立的临床监测员判定是否发生 sICH，并由独立的神经放射科医生审查所有图像。停止规则是前19名患者内发生3次sICH或29名患者内发生4次sICH。结果-从2013年10月至2014年12月，入组了27名AIS患者。中位年龄为 73 岁（范围，34-85；四分位距，65-80），美国国立卫生研究院卒中量表评分中位为 12（范围，6-26；四分位距，9-16）。观察到 1 例 sICH（3.7%；95% 置信区间，0.7%-18%）。结论 - 这些结果表明，全剂量 r-tPA 联合依替巴肽的安全性与单用 r-tPA 的 sICH 历史发生率相当，并支持开展一项 3 期试验，评估全剂量 r-tPA 联合依替巴肽改善 AIS 后的结局。
Background and Purpose-The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator (r-tPA; CLEAR) in Acute Ischemic Stroke (AIS) and CLEAR-Enhanced Regimen (CLEAR-ER) trials demonstrated safety of reduced dose r-tPA plus the glycoprotein 2b/3a inhibitor, eptifibatide, in AIS compared with r-tPA alone. The objective of the CLEAR-Full Dose Regimen (CLEAR-FDR) trial was to estimate the rate of symptomatic intracerebral hemorrhage (sICH) in AIS patients treated with the combination of full-dose r-tPA plus eptifibatide.Methods-CLEAR-FDR was a single-arm, prospective, open-label, multisite study. Patients aged 18 to 85 years treated with 0.9 mg/kg IV r-tPA within 3 hours of symptom onset were enrolled. After obtaining consent, eptifibatide (135 mu g/kg bolus and 2-hour infusion at 0.75 mu g/kg per minute) was administered. The primary end point was the proportion of patients who experienced sICH within 36 hours. An independent clinical monitor adjudicated if an sICH had occurred and an independent neuroradiologist reviewed all images. The stopping rule was 3 sICHs within the first 19 patients or 4 sICHs within 29 patients.Results-From October 2013 to December 2014, 27 patients with AIS were enrolled. Median age was 73 years (range, 34-85; interquartile range, 65-80) and median National Institute of Health stroke scale score was 12 (range, 6-26; interquartile range, 9-16). One sICH (3.7%; 95% confidence interval, 0.7%-18%) was observed.Conclusions-These results demonstrate comparable safety of full-dose r-tPA plus eptifibatide with historical rates of sICH with r-tPA alone and support proceeding with a phase 3 trial evaluating full-dose r-tPA combined with eptifibatide to improve outcomes after AIS.