Infusion of Prostacyclin vs Placebo for 72-hours in Mechanically Ventilated Patients With Acute Respiratory Failure
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Iloprost, Isotonic saline.
- Who it may be relevant to
- Registry conditions: Acute Respiratory Failure, Endothelial Dysfunction, Pulmonary Infection. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Denmark
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
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
Overview
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.
Detailed description
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.
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) will address protocol specific procedures.
Interventions
- Drug Iloprost
Continuously infusion for 72 hours at 3 ml/hours. Treatment dose 1 ng/kg/min - Drug Isotonic saline
Continuously infusion for 72 hours at 3 ml/hours
Primary outcome measures
- 28-day mortality [Time frame: Day 28]
Secondary outcome measures (6)
- 90-day mortality [Time frame: Day 90]
- Vasopressor-free days [Time frame: Until ICU discharge, maximun 90 days after randomization]]
- Renal replacement-free days [Time frame: Until ICU discharge, maximun 90 days after randomization]]
- Mechanical ventilation free days [Time frame: Until ICU discharge, maximun 90 days after randomization]]
- Serious adverse reactions (SARs) [Time frame: Until day 7 after randomization]
- Serious adverse events (SAEs) [Time frame: Until day 7 after randomization]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
Denmark · 5 centers
- Dept. of Anaesthesia and Intensive Care, Bispebjerg Hospital — Copenhagen
- Dept. of Intensive Care, Copenhagen University Hospital Herlev — Herlev
- Dept. of Anaesthesia and Intensive Care, Nordsjaelands Hospital — Hillerød
- Dept. of Intensive care, Hvidovre Hospital — Hvidovre
- Department of Anesthesia and Intensive Care Medicine, Zealand University Hospital — Køge
Identifiers
NCT: NCT06319274 · COMBAT-ARF