NCT06319274

Infusion of Prostacyclin vs Placebo for 72-hours in Mechanically Ventilated Patients With Acute Respiratory Failure

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 450 (estimated)
• Sponsor: Pär Johansson · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Acute Respiratory Failure
• Endothelial Dysfunction
• Pulmonary Infection

Interventions

Type	Name	Description
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

Timeline

• Start date: 2024-04-15
• Primary completion: 2027-09-30
• Completion: 2027-09-30
• First posted: 2024-03-20
• Last updated: 2025-08-22

Locations

5 sites across 1 country: Denmark