Infusion of Prostacyclin (Iloprost) vs Placebo for 72-hours in COVID-19 Patients With Respiratory Failure

NCT04420741 | Completed Phase 2

• 2 other identifiers: COMBAT-COVID-192020-001296-33
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this trial is to investigate the efficacy and safety of continuous intravenous administration of low dose iloprost versus placebo for 72-hours, in 80 patients with COVID-19 suffering from 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 COVID-19 patients suffering from respiratory failure caused by endothelial breakdown, ultimately improving survival. 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 COMBAT-COVID-19.

Conditions

COVID-19; Respiratory Failure

Keywords

COVID-19; SHINE; Endotheliopathy

Outcome Measures

Primary Outcomes (1)

• Mechanical ventilation free days

  Days alive without mechanical ventilation in the ICU within 28 days

  Until ICU discharge, maximun 28 days after randomization

Secondary Outcomes (7)

• 28 and 90-day mortality

  Day 28 and 90 after randomization

• Modified Sequential Organ Failure Assessment (SOFA)

  Until ICU discharge, maximun 90 days after randomization

• 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

Study Arms (2)

Iloprost

EXPERIMENTAL

Patients randomized to active treatment (n=40 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=40 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 (aged 18 years or above)
• Confirmed COVID-19 infection
• Need for mechanical ventilation (\< 72 hours at time of screening)
• Soluble thrombomodulin (sTM) ≥ 4 ng/mL

You may not qualify if:

• Withdrawal from active therapy
• Pregnancy (non-pregnancy confirmed by patient being postmenopausal (age 60 or above) or having a negative urine- or plasma-hCG)
• Known hypersensitivity to iloprost or to any of the other ingredients.
• Previously included in this trial or a prostacyclin trial within 30 days
• Consent cannot be obtained
• 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, Denmark

Location

Dept. of Intensive Care, Copenhagen University Hospital, Rigshospitalet

Copenhagen, Denmark

Location

Dept. of Intensive Care, Copenhagen University Hospital Herlev

Herlev, Denmark

Location

Dept. of Anaesthesia and Intensive Care, Nordsjaelands Hospital

Hillerød, Denmark

Location

Dept. of Anaesthesia and Intensive Care, Hvidovre Hospital

Hvidovre, Denmark

Location

Related Publications (2)

• Johansson PI, Soe-Jensen P, Bestle MH, Clausen NE, Kristiansen KT, Lange T, Stensballe J, Perner A. Prostacyclin in Intubated Patients with COVID-19 and Severe Endotheliopathy: A Multicenter, Randomized Clinical Trial. Am J Respir Crit Care Med. 2022 Feb 1;205(3):324-329. doi: 10.1164/rccm.202108-1855OC.

  PMID: 34813414 BACKGROUND

• Johansson PI, Bestle M, Soe-Jensen P, Kristiansen KT, Stensballe J, Clausen NE, Perner A. The effect of prostacyclin (Iloprost) infusion at a dose of 1 ng/kg/min for 72 hours compared to placebo in mechanically ventilated patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial. Trials. 2020 Aug 26;21(1):746. doi: 10.1186/s13063-020-04696-2.

  PMID: 32847626 RESULT

MeSH Terms

Conditions

COVID-19; Respiratory Insufficiency

Interventions

Iloprost; Sodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

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

• Anders Perner, MD, PhD

  Copenhagen University Hospital, Intensive care Unit 4131

  PRINCIPAL INVESTIGATOR

• Pär I Johansson, MD, DMSc

  Copenhagen University Hospital, Capital Blood Bank 2034

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The preparation will be done by an unblinded study nurse at the respective ICU´s, who will be responsible for preparing the investigational drug so that it can be administered in 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 on how the fluid looks and behaves.
• 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: June 4, 2020
• First Posted: June 9, 2020
• Study Start: June 15, 2020
• Primary Completion: February 23, 2021
• Study Completion: April 23, 2021
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (5)