Efficacy and Safety of 72-hour Infusion of Prostacyclin (1 ng/kg/Min) in Mechanically Ventilated Patients With Infectious Pulmonary Endotheliopathy - a Multicenter Randomized, Placebo-controlled, Blinded, Investigator-initiated Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 450
- 试验地点
- 5
- 主要终点
- 28-day mortality
研究概览
简要总结
The purpose of this clinical trial is to investigate the efficacy and safety of continuous intravenous administration of low dose iloprost versus placebo for 72-hours, in 450 mechanically ventilated patients with infectious respiratory failure. The study hypothesis is that iloprost may be beneficial as an endothelial rescue treatment as it is anticipated to deactivate the endothelium and restore vascular integrity in patients suffering from respiratory failure caused by endothelial breakdown, ultimately improving survival.
详细描述
Acute respiratory failure (ARF) is common in critically ill patients and 50% of all intensive care unit patients require mechanical ventilation. ARF occurs in a heterogenous patient group, most often in the setting of pneumonia, sepsis, aspiration of gastric contents or severe trauma and major surgery. Despite improvements in intensive care capabilities, ARF mortality remains high and the only treatment option, to date, is supportive care. A recent Cochrane analysis (2018) found no evidence for that any drug was effective in reducing deaths in mechanically ventilated patients with ARF, highlighting the high unmet medical need.
Given that the pulmonary system, apart from the brain, is the most highly vascularized vital organ in the body, extensive endothelial damage is a central feature of acute respiratory distress syndrome (ARDS) with respiratory failure being the rationale for the current study. Evidence support that iloprost infusion significantly improved endothelial function and integrity in mechanically ventilated patients with COVID-19 infection with reducing 28-day mortality by 50%.
The main objective in this clinical trial is to investigate whether continuous infusion of low dose iloprost at a dose of 1 ng/kg/min for 72-hours is safe and significantly reduce all-cause mortality at day 28.
Patients that are eligible for this trial will be temporarily incompetent due to acute severe illness relating to respiratory failure.
During the trial, patient will be given continuous infusion of low dose iloprost or placebo for 72 hours during their stay at the intensive care unit (ICU) and additional blood samples will be obtained at baseline, 24-, 48 and 72-hours.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) The preparation will be done by an unblinded study nurse independent of the including ICU´s, who will be responsible for preparing the investigational drug to be administered in a blinded fashion. Iloprost is a colorless fluid that is to be diluted in 0.9% saline. The infusion pump containing diluted active drug and placebo will be identical in both looks and behavior.
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
- •Adult intensive care patients (age ≥ 18 years)
- •Suspected pulmonary infection
- •Need for mechanical ventilation (< 24 hours from time of screening)
- •soluble thrombomodulin (sTM) ≥ 4 ng/mL in blood plasma
排除标准
- •Withdrawal from active therapy
- •Pregnancy (non-pregnancy confirmed by patient having a negative urine- or plasma Choriogonadotropin (hCG) or being postmenopausal defined as females at 60 years old or beyond or at the investigators discretion)
- •Septic shock according to the Sepsis 3 criteria AND a sTM> 10 ng/ml
- •Known hypersensitivity to iloprost or to any of the other ingredients.
- •Previously included in this trial or a prostacyclin trial within 30 days
- •Life-threatening bleeding defined by the treating physician
- •Known severe heart failure (NYHA class IV)
- •Suspected acute coronary syndrome
研究组 & 干预措施
Iloprost
Patients randomized to active treatment (n=225 patients) will receive continuous infusion of iloprost for 72 hours after inclusion or until discharge to ward or death, whichever comes first.
干预措施: Iloprost (Drug)
Isotonic saline
Patients randomized to placebo treatment (n=225 patients) will receive continuous infusion of placebo for 72 hours after inclusion or until discharge to ward or death, whichever comes first.
干预措施: Isotonic saline (Drug)
结局指标
主要结局
28-day mortality
时间窗: Day 28
All-cause mortality at day 28
次要结局
- 90-day mortality(Day 90)
- Vasopressor-free days(Until ICU discharge, maximun 90 days after randomization])
- Serious adverse events (SAEs)(Until day 7 after randomization)
- Mechanical ventilation free days(Until ICU discharge, maximun 90 days after randomization])
- Serious adverse reactions (SARs)(Until day 7 after randomization)
- Renal replacement-free days(Until ICU discharge, maximun 90 days after randomization])
研究者
Pär Johansson
Sponsor
Rigshospitalet, Denmark