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 .

中文翻译：

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序贯多次递增剂量索那肽治疗中度至重度 ARDS 患者肺通透性水肿的安全性和初步疗效——一项随机、安慰剂对照、双盲试验

急性呼吸窘迫综合征 (ARDS) 是一种复杂的临床诊断，具有多种可能的病因。然而，一个共同特征是肺通透性水肿，这会导致肺泡扩散途径增加，从而导致氧合和脱羧受损。在一项 I 期临床试验中，一种新型吸入肽制剂（AP301，solnatide）被证明可以显着减少 ARDS 动物模型中的肺水肿，并且可以安全地用于健康人类。在这里，我们提出了一项 IIB 期临床试验的协议，该试验旨在调查 ARDS 患者的安全性和未来可能的疗效终点。这是一项随机、安慰剂对照、双盲干预研究。需要机械通气的中度至重度 ARDS 患者将被随机分配到平行组，分别接受递增剂量的索那肽或安慰剂。在提高到更高剂量之前，数据安全监测委员会将调查以前患者的数据，以了解是否存在违反患者安全的任何迹象。干预（研究药物的应用）在 7 天内每天进行两次，随后是另外 21 天的随访期。纳入本试验的患者病情严重，需要机械通气。在筛选和干预阶段期间要收集的数据量很大，纳入任何特定患者的潜在时间框架很短。但是，如果准备得当，遵守该协议将有助于获取可靠的数据。需要特别注意知情同意，因为符合条件的患者在纳入时很可能处于昏迷和/或深度镇静状态。该试验在欧盟临床试验登记处（clinicaltrialsregister.eu）进行了前瞻性注册。EudraCT编号：2017-003855-47。