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

NCT06319274 | Recruiting Phase 2 DMC

• 1 other identifier: COMBAT-ARF
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 5

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.

Conditions

Acute Respiratory Failure; Endothelial Dysfunction; Pulmonary Infection

Keywords

Endotheliopathy; SHINE

Outcome Measures

Primary Outcomes (1)

• 28-day mortality

  All-cause mortality at day 28

  Day 28

Secondary Outcomes (6)

• 90-day mortality

  Day 90

• 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

Study Arms (2)

Iloprost

EXPERIMENTAL

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.

Drug: Iloprost

Isotonic saline

PLACEBO COMPARATOR

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.

Drug: Isotonic saline

Interventions

Iloprost DRUG

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

Also known as: Ilomedin

Iloprost

Isotonic saline DRUG

Continuously infusion for 72 hours at 3 ml/hours

Isotonic saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pär Johansson: lead

Study Sites (5)

Dept. of Anaesthesia and Intensive Care, Bispebjerg Hospital

Copenhagen, 2400, Denmark

RECRUITING

Dept. of Intensive Care, Copenhagen University Hospital Herlev

Herlev, 2730, Denmark

RECRUITING

Dept. of Anaesthesia and Intensive Care, Nordsjaelands Hospital

Hillerød, 3400, Denmark

RECRUITING

Dept. of Intensive care, Hvidovre Hospital

Hvidovre, 2650, Denmark

RECRUITING

Department of Anesthesia and Intensive Care Medicine, Zealand University Hospital

Køge, 4600, Denmark

RECRUITING

MeSH Terms

Interventions

Iloprost; Sodium Chloride

Intervention Hierarchy (Ancestors)

Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Pär I Johansson, MD, DMSc

  Rigshospitalet, Denmark

  STUDY DIRECTOR

• Peter Soee-Jensen, MD

  +4538682458

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pär I Johansson, MD, DMSc

CONTACT

+4535452030; per.johansson@regionh.dk

Kristine H Pedersen, MSc. Pharm.

CONTACT

+4535453489; kristine.holst.pedersen.01@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor

Model Details: Randomization active/placebo (1:1) parallel arms

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 20, 2024
• Study Start: April 15, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: August 22, 2025

Record last verified: 2025-08

Locations

DK (5)