Study of alteplase for respiratory failure in severe acute respiratory syndrome coronavirus 2/COVID-19: Study design of the phase IIa STARS trial
Study of alteplase for respiratory failure in severe acute respiratory syndrome coronavirus 2/COVID-19: Study design of the phase IIa STARS trial
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DOI：
10.1002/rth2.12395
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发表时间：
2020-08-19
影响因子：
4.6
通讯作者：
Yaffe, Michael B.
中科院分区：
文献类型：
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作者：
Moore, Hunter B.;Barrett, Christopher D.;Yaffe, Michael B.
背景2019冠状病毒病（COVID-19）大流行导致急性呼吸窘迫综合征（ARDS）大幅激增。之前的I期试验（非COVID-19）证明了使用纤溶治疗的ARDS患者的肺功能改善。现在需要使用广泛使用的组织型纤溶酶原激活剂（t-PA）阿替普酶进行随访试验，以评估该危重患者人群的最佳剂量和安全性。目的描述评价阿替普酶治疗中/重度COVID-19所致ARDS的安全性和有效性的IIa期试验的设计和原理。患者/方法将进行一项快速适应、实用、开放标签、随机、对照、IIa期临床试验，分为3组：静脉注射阿替普酶50 mg、静脉注射阿替普酶100 mg和对照（标准治疗）。入选标准为已知/疑似COVID-19感染，尽管进行了最大机械通气管理，但PaO 2/FiO（2）比值> 4小时。阿替普酶将通过50 mg或100 mg初始推注给药，随后输注肝素进行全身抗凝，如果PaO 2/FiO（2）改善>20%但未持续24小时，则重新给药阿替普酶。结果主要观察指标为随机分组后48 h PaO 2/FiO（2）的改善。其他结局包括无呼吸机和重症监护室天数、成功拔管（无重新插管
Background The coronavirus disease 2019 (COVID-19) pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non-COVID-19) demonstrated improvement in pulmonary function in patients ARDS using fibrinolytic therapy. A follow-up trial using the widely available tissue-type plasminogen activator (t-PA) alteplase is now needed to assess optimal dosing and safety in this critically ill patient population. Objective To describe the design and rationale of a phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID-19-induced ARDS. Patients/Methods A rapidly adaptive, pragmatic, open-label, randomized, controlled, phase IIa clinical trial will be conducted with 3 groups: intravenous alteplase 50 mg, intravenous alteplase 100 mg, and control (standard-of-care). Inclusion criteria are known/suspected COVID-19 infection with PaO2/FiO(2)ratio 4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50 mg or 100 mg followed by heparin infusion for systemic anticoagulation, with alteplase redosing if there is a >20% PaO2/FiO(2)improvement not sustained by 24 hours. Results The primary outcome is improvement in PaO2/FiO(2)at 48 hours after randomization. Other outcomes include ventilator- and intensive care unit-free days, successful extubation (no reintubation