Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS - a Randomised, Placebo-controlled, Double-blind Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 92
- 试验地点
- 15
- 主要终点
- Safety endpoint: Any cause death
研究概览
简要总结
This phase IIb, randomized, placebo-controlled, double-blind, dose escalation study will assess the local and systemic safety of 7 days orally inhaled sequential multiple ascending doses of solnatide in patients with pulmonary permeability oedema and moderate-to-severe ARDS and review potential efficacy endpoints for a future phase III pivotal trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent
- •Male or female ≥18 years of age.
- •Patient has been admitted to an ICU, is mechanically ventilated (according to the ventilation and weaning protocol in Appendix I) and stable in this condition for at least 8 hours.
- •Moderate-to-severe ARDS diagnosis as defined by the Berlin Definition:
- •Onset of ARDS within 1 week of a known clinical insult or new or worsening respiratory symptoms.
- •Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules.
- •Respiratory failure not fully explained by cardiac failure or fluid overload (origin of oedema).
- •PaO2/FiO2 ≤ 200 mm Hg with Positive End-Expiratory Pressure (PEEP) ≥5 cm H2O.
- •ARDS diagnosis not older than 48 hours.
- •Extravascular lung water index (EVLWI) ≥ 10 ml/PBW as assessed with a validated bedside measurement (single indicator transpulmonary thermodilution measurement with the PiCCO® system).
- •Patient who meets criteria for extensive hemodynamic monitoring as per international intensive care medicine standards.
- •For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided.
- •Male and Female (WOCBP) patients using adequate contraception.
排除标准
- •History of clinically relevant allergies or idiosyncrasies to solnatide.
- •Known use of any other investigational or non-registered drug within 30 days prior to study enrolment.
- •Severe state of septic shock with a Mean Arterial Pressure (MAP) ≤ 65 mm Hg and a serum lactate level > 4 mmol/L (36 mg/dL) despite adequate volume resuscitation.
- •An underlying clinical condition that, in the opinion of the Investigator, would make it very unlikely for the patient to be successfully weaned from ventilation due to severe underlying diseases (e.g. severe malnutrition, severe neurological diseases, pulmonary fibrosis or COPD).
- •Extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support. In no way are patients to be denied or delayed these procedures to avoid exclusion from the study.
- •Neutrophil count < 0.3 x 109/L.
- •Cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks.
- •Cachexia (BMI < 18.5 kg/m2).
- •Cardiogenic pulmonary oedema diagnosed by echocardiography or pulmonary artery catheter.
- •Severe skin burns involving more than 15% of body surface.
- •Subjects who are extremely unlikely to survive more than 48 hours due to the acute conditions of the patient in the opinion of the Investigator.
- •Subjects transferred from a hospital not participating in this study who are already planned to be re-transferred during the observation period.
- •Subjects who are not expected to survive the next month because of an underlying uncorrectable medical condition or a do not resuscitate order.
- •Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.
研究组 & 干预措施
Solnatide 5mg
Solnatide 25 mg powder for reconstitution for solution for inhalation. 5mg administered
干预措施: Solnatide 25 mg powder for reconstitution for solution for inhalation (Drug)
Solnatide 60mg
Solnatide 25 mg powder for reconstitution for solution for inhalation. 60mg administered
干预措施: Solnatide 25 mg powder for reconstitution for solution for inhalation (Drug)
Solnatide 125mg
Solnatide 25 mg powder for reconstitution for solution for inhalation. 125mg administered
干预措施: Solnatide 25 mg powder for reconstitution for solution for inhalation (Drug)
Placebo
0,9% saline solution
干预措施: 0.9% Saline Solution (Drug)
结局指标
主要结局
Safety endpoint: Any cause death
时间窗: Randomisation - day 28
Primary Safety Endpoint: Composite endpoint including any cause death at day 28
Safety endpoint: Drug-related adverse events
时间窗: Randomisation - day 14
Primary Safety Endpoint: Composite endpoint including drug-related adverse events through day 14
Safety endpoint: All adverse events
时间窗: Randomisation - day 28
Primary Safety Endpoint: Composite endpoint including all adverse events through day 28
次要结局
- EVLWI(baseline - day 7)
- PVPI(baseline - day 7)
- Change of ventilatory settings(baseline - day 14)
- Murray lung injury score(baseline - day 7)
- Oxygenation ratio (PaO2 / FiO2 ratio)(baseline - day 7)
- Time to extubation(baseline - day 28)
- Ventilator-free days (VFD)(baseline - day 28)
- Days of hospitalization and in ICU(baseline - day 28)