A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke
A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke
复制标题
DOI：
10.1161/01.str.0000154872.73240.e9
复制
发表时间：
2005-03-01
期刊：
影响因子：
8.3
通讯作者：
Hemmen, TM
中科院分区：
文献类型：
--
作者：
Haley, EC;Lyden, PD;Hemmen, TM
背景和目的-重组组织型纤溶酶原激活剂（rtPA）是唯一被批准的急性缺血性中风治疗方法。然而，接受 rtPA 治疗的患者中有 6.4% 发生脑出血 (ICH)，这限制了其使用。替奈普酶 (TNK) 是 rtPA 的改良形式，具有更长的半衰期和更高的纤维蛋白特异性。与 rtPA 相比，心肌梗死后患者接受 TNK 治疗时全身出血较少。这项开放标签、剂量递增的安全性研究旨在开发 TNK 治疗缺血性中风的初步经验。方法——符合条件的患者在中风发作 3 小时内接受静脉推注 TNK 治疗。剂量递增是在 25 名患者中进行的，从 0.1 mg/kg 开始，到计划的最大剂量 0.6 mg/kg。主要终点是治疗 36 小时内出现症状性颅内出血。所有患者均随访 3 个月。结果-八十八 (88) 名患者接受 4 个剂量级别的治疗。在前 3 组（0.1、0.2、0.4 mg/kg）各 25 名患者中，没有出现症状，出现 2 名（8%）、8 名（32%）和 7 名（28%）无症状 ICH。在 13 名患者中 2 名 (15%) 出现症状、3 名 (23%) 出现无症状 ICH 后，0.5 mg/kg 的第四级入组结束。总体而言，3 个月时的改良 Rankin 评分与接受 rtPA 治疗的历史对照相似，并且治疗组之间没有显着差异。结论 - 0.1 至 0.4 mg/kg 的 TNK 剂量对于缺血性中风是安全的。未来的试验需要比较 TNK 与 rtPA 相比对神经系统结果和安全性的影响。
Background and Purpose-Recombinant tissue-type plasminogen activator (rtPA) is the only approved treatment in acute ischemic stroke. However, intracerebral hemorrhage (ICH) occurs in 6.4% of patients treated with rtPA and limits its use. Tenecteplase (TNK) is a modified form of rtPA, with longer half-life and greater fibrin specificity. Patients after myocardial infarction had fewer systemic hemorrhages when treated with TNK compared with rtPA. This open-label, dose-escalation safety study was conducted to develop initial experience with TNK in the treatment of ischemic stroke.Methods-Eligible patients were treated with an intravenous bolus infusion of TNK within 3 hours of stroke onset. The dose escalation was conducted in tiers of 25 patients, starting at 0.1 mg/kg, to a planned maximum of 0.6 mg/kg. The primary endpoint was symptomatic intracranial hemorrhage within 36 hours of treatment. All patients were followed-up for 3 months.Results-Eighty-eight (88) patients were treated in 4 dosing tiers. In the first 3 tiers (0.1, 0.2, 0.4 mg/kg) of 25 patients each, no symptomatic and 2 (8%), 8 (32%), and 7 (28%) asymptomatic ICHs occurred. Enrollment into the fourth tier at 0.5 mg/kg was closed after 2 of 13 patients (15%) had symptomatic and 3 (23%) had asymptomatic ICHs. Overall, modified Rankin scores at 3 months were similar to those of historical controls treated with rtPA and not significantly different between treatment groups.Conclusions-TNK doses of 0.1 to 0.4 mg/kg are safe in ischemic stroke. Future trials are needed to compare the effect of TNK on neurological outcome and safety as compared with rtPA.