Efficacy and Safety of 72-hour Infusion of Prostacyclin (1 Nanogram(ng)/ Kilo(kg)/Minute(Min)) in Patients With COVID-19 Induced Pulmonary Endotheliopathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 5
- 主要终点
- Mechanical ventilation free days
研究概览
简要总结
The purpose of this trial is to investigate the efficacy and safety of continuous intravenous administration of low dose iloprost versus placebo for 72-hours, in 80 patients with COVID-19 suffering from 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 COVID-19 patients suffering from respiratory failure caused by endothelial breakdown, ultimately improving survival. 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 COMBAT-COVID-19.
详细描述
Patients with the most severe type of sepsis, those with septic shock have a mortality rate between 30% to 45% due to multiple organ failure. The poor outcome of shocked patients, and especially those with sepsis, may by related to microvascular endothelial dysfunction.
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by coronavirus 2 (SARS-CoV-2) and, thus, being a novel cause of sepsis. The disease was first identified in 2019 in Wuhan, the capital of Hubei, China, and has since spread globally, resulting in the 2019-20 coronavirus pandemic. Common symptoms include fever, cough and shortness of breath, muscle pain and sputum production. While many cases result in mild symptoms, some progress to pneumonia and multi-organ failure. In particular COVID-19 is associated with ARDS with respiratory failure and high mortality.
Evidence support that iloprost infusion significantly improved endothelial function and integrity, The main objective in this trial is to investigate whether continuous infusion of lov dose iloprost at a dose of 1 ng/kg/min for 72-hours is safe and significantly reduce the need of respiratory support in the intensive care unit (ICU) compared to infusion of placebo in patients with COVID-19 induced pulmonary endotheliopathy (SHINE).
Patients that are eligible for this trial will be temporarily incompetent due to acute severe illness relating to respiratory failure, therefore informed consent will be obtained from a scientific guardian. Next-of kin and subsequently the patient will co-sign as soon as possible hereafter. During the trial, patient will be given continuous infusion of low dose iloprost or placebo for 72 hours and additional blood samples will be obtained at baseline and at 24 hours. Follow up on respiratory failure and mortality will be performed on dag 28 and 90.
This trial is conducted in accordance with the Helsinki 2 Declaration and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Guideline for Good Clinical Practice (ICH-GCP) and in compliance with the protocol. As part of the quality assurance on-site monitoring visit will be performed by the an independent GCP-unit including source data verification. Standard Operation Procedure (SOP) to address protocol specific procedures such as data collection and adverse event reporting are developed.
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
The preparation will be done by an unblinded study nurse at the respective ICU´s, who will be responsible for preparing the investigational drug so that it can be administered in 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 on how the fluid looks and behaves.
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 (aged 18 years or above)
- •Confirmed COVID-19 infection
- •Need for mechanical ventilation (< 72 hours at time of screening)
- •Soluble thrombomodulin (sTM) ≥ 4 ng/mL
排除标准
- •Withdrawal from active therapy
- •Pregnancy (non-pregnancy confirmed by patient being postmenopausal (age 60 or above) or having a negative urine- or plasma-hCG)
- •Known hypersensitivity to iloprost or to any of the other ingredients.
- •Previously included in this trial or a prostacyclin trial within 30 days
- •Consent cannot be obtained
- •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=40 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=40 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
Mechanical ventilation free days
时间窗: Until ICU discharge, maximun 28 days after randomization
Days alive without mechanical ventilation in the ICU within 28 days
次要结局
- 28 and 90-day mortality(Day 28 and 90 after randomization)
- Modified Sequential Organ Failure Assessment (SOFA)(Until ICU discharge, maximun 90 days after randomization)
- Vasopressor free days(Until ICU discharge, maximun 90 days after randomization)
- Renal replacement free days(Until ICU discharge, maximun 90 days after randomization)
- Mechanical ventilation free days(Until ICU discharge, maximun 90 days after randomization)
- Serious adverse reactions (SARs)(Until day 7 after randomization)
- Serious adverse events (SAEs)(Until day 7 after randomization)
研究者
Pär Johansson
Sponsor
Rigshospitalet, Denmark