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

NCT ID: NCT06319274

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 450 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-15
• Study Completion Date: 2027-09-30

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Iloprost

Intervention Type: DRUG

Continuously infusion for 72 hours at 3 ml/hours. Treatment dose 1 ng/kg/min

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.

Group Type: PLACEBO_COMPARATOR

Isotonic saline

Intervention Type: DRUG

Continuously infusion for 72 hours at 3 ml/hours

Interventions

Iloprost

Continuously infusion for 72 hours at 3 ml/hours. Treatment dose 1 ng/kg/min

Intervention Type: DRUG

Isotonic saline

Continuously infusion for 72 hours at 3 ml/hours

Intervention Type: DRUG

Other Intervention Names

Ilomedin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pär Johansson

OTHER

Sponsor Role: lead

Responsible Party

Pär Johansson

Sponsor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Pär I Johansson, MD, DMSc

Role: STUDY_DIRECTOR

Rigshospitalet, Denmark

Peter Soee-Jensen, MD

Role: PRINCIPAL_INVESTIGATOR

+4538682458

Locations

Dept. of Anaesthesia and Intensive Care, Bispebjerg Hospital

Copenhagen, , Denmark

Site Status: RECRUITING

Dept. of Intensive Care, Copenhagen University Hospital Herlev

Herlev, , Denmark

Site Status: RECRUITING

Dept. of Anaesthesia and Intensive Care, Nordsjaelands Hospital

Hillerød, , Denmark

Site Status: RECRUITING

Dept. of Intensive care, Hvidovre Hospital

Hvidovre, , Denmark

Site Status: RECRUITING

Department of Anesthesia and Intensive Care Medicine, Zealand University Hospital

Køge, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Pär I Johansson, MD, DMSc

Role: CONTACT

per.johansson@regionh.dk

+4535452030

Kristine H Pedersen, MSc. Pharm.

Role: CONTACT

kristine.holst.pedersen.01@regionh.dk

+4535453489

Facility Contacts

Niels E Clausen, MD

Role: primary

Peter Soee-Jensen, MD

Role: primary

Morten Bestle, MD

Role: primary

Klaus T Kristiansen, MD

Role: primary

klaus.tjelle.kristiansen.02@regionh.dk

+4538620394

Lars Peter K Andersen, MD, PhD

Role: primary

Other Identifiers

COMBAT-ARF

Identifier Type: -

Identifier Source: org_study_id