Acute Respiratory FailurePhase 2COMBAT-ARFNCT06319274
Infusion of Prostacyclin vs Placebo for 72-hours in Mechanically Ventilated Patients With Acute Respiratory Failure
A Phase 2 study testing Iloprost and Isotonic saline in people with Acute Respiratory Failure and Endothelial Dysfunction, run by Pär Johansson at 5 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Failure, Endothelial Dysfunction, Pulmonary Infection
- What is being tested?
- Iloprost and Isotonic saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 450 participants
- Where
- 5 sitesDenmark
- Study dates
- 15 Apr 2024to 30 Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Denmark5 sites, 5 recruiting
- Recruiting
Dept. of Anaesthesia and Intensive Care, Bispebjerg Hospital
Copenhagen, 2400
Niels E Clausen, MD
Niels E Clausen, MD
- Recruiting
Dept. of Intensive Care, Copenhagen University Hospital Herlev
Herlev, 2730
Peter Soee-Jensen, MD
Peter Soee-Jensen, MD
- Recruiting
Dept. of Anaesthesia and Intensive Care, Nordsjaelands Hospital
Hillerød, 3400
Morten Bestle, MD
Morten Bestle, MD
- Recruiting
Dept. of Intensive care, Hvidovre Hospital
Hvidovre, 2650
Klaus T Kristiansen, MD, +4538620394, klaus.tjelle.kristiansen.02@regionh.dk
Klaus T Kristiansen, MD
- Recruiting
Department of Anesthesia and Intensive Care Medicine, Zealand University Hospital
Køge, 4600
Lars Peter K Andersen, MD, PhD
Lars Peter K Andersen, MD, PhD
About this study
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
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.
Read the 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.
- Being tested
- Iloprost, Isotonic saline
- Keywords
- Endotheliopathy, SHINE
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IloprostDrug
Also called Ilomedin
Continuously infusion for 72 hours at 3 ml/hours. Treatment dose 1 ng/kg/min
Isotonic salineDrug
Continuously infusion for 72 hours at 3 ml/hours
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Isotonic saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
28-day mortality
All-cause mortality at day 28
Measured: Day 28
Secondary outcomes (6)
90-day mortality
All-cause mortality at day 90
Measured: Day 90
Vasopressor-free days
Days alive without vasopressor in the ICU within 28- and 90 days
Measured: Until ICU discharge, maximun 90 days after randomization]
Renal replacement-free days
Days alive without renal replacement in the ICU within 28- and 90 days
Measured: Until ICU discharge, maximun 90 days after randomization]
Mechanical ventilation free days
Days alive without mechanical ventilation in the ICU within 28- and 90 days
Measured: Until ICU discharge, maximun 90 days after randomization]
Serious adverse reactions (SARs)
Total number and numbers of patient with one or more serious adverse reactions within the first 7 days
Measured: Until day 7 after randomization
Serious adverse events (SAEs)
Total numbers and numbers of patients with one or more serious adverse events within the first 7 days
Measured: Until day 7 after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2024
- Study start15 Apr 2024
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomization active/placebo (1:1) parallel arms
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pär Johansson
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Pär Johansson, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Pär I Johansson, MD, DMSc, Study director, Copenhagen University Hospital, RigshospitaletPeter Soee-Jensen, MD, Principal investigator, +4538682458
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06319274
- Sponsor's protocol ID
- COMBAT-ARF
- Acronym
- COMBAT-ARF
- Status last verified
- Aug 2025
- First submitted
- 13 Mar 2024
- Last updated
- 22 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06319274
- Acronym / sponsor ID
- COMBAT-ARF / COMBAT-ARF
- Keywords
- Endotheliopathy, SHINE
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Pär JohanssonUniversity, hospital or other
- Study start
- 15 Apr 2024 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 20 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomization active/placebo (1:1) parallel arms
| Arm | Type | Receives |
|---|---|---|
| Iloprost | Experimental | Drug: IloprostPatients 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. |
| Isotonic saline | Placebo comparator | Drug: Isotonic salinePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IloprostAlso: IlomedinContinuously infusion for 72 hours at 3 ml/hours. Treatment dose 1 ng/kg/min | Drug | Iloprost |
| Isotonic salineContinuously infusion for 72 hours at 3 ml/hours | Drug | Isotonic saline |
Primary outcome
28-day mortality
Time frame: Day 28
All-cause mortality at day 28
6 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pär I Johansson, MD, DMSc study director
Copenhagen University Hospital, Rigshospitalet
Peter Soee-Jensen, MD principal investigator
+4538682458
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Iloprost and Isotonic saline in people with Acute Respiratory Failure and Endothelial Dysfunction, run by Pär Johansson at 5 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pär I Johansson, MD, DMSc (+4535452030, per.johansson@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
28-day mortality (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2025.