Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
Department of Anaesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria.
Trials. 2021 Sep 20;22(1):643. doi: 10.1186/s13063-021-05588-9.
Acute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a Phase I clinical trial. Here, we present the protocol for a Phase IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients.
This is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of 7 days, ensued by a follow-up period of another 21 days.
The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion.
This trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47 .
急性呼吸窘迫综合征（ARDS）是一种具有多种潜在病因的复杂临床诊断。然而，其共同的特征是肺通透性水肿，导致肺泡扩散途径增加，随后出现氧合和脱羧功能受损。一种新型吸入性肽制剂（AP301，solnatide）在 ARDS 的动物模型中显著减轻肺水肿，并在 I 期临床试验中对健康人群进行安全给药。在这里，我们提出了一项 IIB 期临床试验的方案，旨在研究 ARDS 患者的安全性和可能的未来疗效终点。
这是一项随机、安慰剂对照、双盲干预研究。需要机械通气的中重度 ARDS 患者将被随机分为两组，分别接受递增剂量的 solnatide 或安慰剂治疗。在推进到更高剂量之前，数据安全监测委员会将调查前一组患者的数据，以确定是否存在任何违反患者安全的迹象。干预（应用研究药物）每天进行两次，共 7 天，随后进行 21 天的随访期。
本试验纳入的患者病情严重，需要机械通气。在筛选和干预阶段，需要收集大量的数据，且纳入任何给定患者的潜在时间窗口很短。然而，只要准备充分，遵循本方案将获得可靠的数据。在获得知情同意时需要特别谨慎，因为符合条件的患者在纳入时可能处于昏迷和/或深度镇静状态。
本试验前瞻性地在欧盟临床试验注册中心（clinicaltrialsregister.eu）注册。EudraCT 编号：2017-003855-47。
