- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04420741
Infusion of Prostacyclin (Iloprost) vs Placebo for 72-hours in COVID-19 Patients With Respiratory Failure (COMBAT-COVID)
Efficacy and Safety of 72-hour Infusion of Prostacyclin (1 Nanogram(ng)/ Kilo(kg)/Minute(Min)) in Patients With COVID-19 Induced Pulmonary Endotheliopathy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Patients with the most severe type of sepsis, those with septic shock have a mortality rate between 30% to 45% due to multiple organ failure. The poor outcome of shocked patients, and especially those with sepsis, may by related to microvascular endothelial dysfunction.
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by coronavirus 2 (SARS-CoV-2) and, thus, being a novel cause of sepsis. The disease was first identified in 2019 in Wuhan, the capital of Hubei, China, and has since spread globally, resulting in the 2019-20 coronavirus pandemic. Common symptoms include fever, cough and shortness of breath, muscle pain and sputum production. While many cases result in mild symptoms, some progress to pneumonia and multi-organ failure. In particular COVID-19 is associated with ARDS with respiratory failure and high mortality.
Evidence support that iloprost infusion significantly improved endothelial function and integrity, The main objective in this trial is to investigate whether continuous infusion of lov dose iloprost at a dose of 1 ng/kg/min for 72-hours is safe and significantly reduce the need of respiratory support in the intensive care unit (ICU) compared to infusion of placebo in patients with COVID-19 induced pulmonary endotheliopathy (SHINE).
Patients that are eligible for this trial will be temporarily incompetent due to acute severe illness relating to respiratory failure, therefore informed consent will be obtained from a scientific guardian. Next-of kin and subsequently the patient will co-sign as soon as possible hereafter. During the trial, patient will be given continuous infusion of low dose iloprost or placebo for 72 hours and additional blood samples will be obtained at baseline and at 24 hours. Follow up on respiratory failure and mortality will be performed on dag 28 and 90.
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) to address protocol specific procedures such as data collection and adverse event reporting are developed.
The number of patients participating is based on a power calculation using the data on days alive and free from mechanical ventilation in the ICU within 28 days from a randomized, double blind, placebo controlled clinical trial in patients with acute respiratory distress syndrome ARDS (NTC 02622724).
The number of patients may be increased if required for regulatory approval for this indication.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Copenhagen, Denmark
- Dept. of Anaesthesia and Intensive Care, Bispebjerg Hospital
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Copenhagen, Denmark
- Dept. of Intensive Care, Copenhagen University Hospital, Rigshospitalet
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Herlev, Denmark
- Dept. of Intensive Care, Copenhagen University Hospital Herlev
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Hillerød, Denmark
- Dept. of Anaesthesia and Intensive Care, Nordsjaelands Hospital
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Hvidovre, Denmark
- Dept. of Anaesthesia and Intensive Care, Hvidovre Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Iloprost
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.
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Continuously infusion for 72 hours at 3 ml/hours.
Treatment dose 1 ng/kg/min
Other Names:
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Placebo Comparator: Isotonic saline
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.
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Continuously infusion for 72 hours at 3 ml/hours
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mechanical ventilation free days
Time Frame: Until ICU discharge, maximun 28 days after randomization
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Days alive without mechanical ventilation in the ICU within 28 days
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Until ICU discharge, maximun 28 days after randomization
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
28 and 90-day mortality
Time Frame: Day 28 and 90 after randomization
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Vital status of the patient at day 28 and day 90
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Day 28 and 90 after randomization
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Modified Sequential Organ Failure Assessment (SOFA)
Time Frame: Until ICU discharge, maximun 90 days after randomization
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Mean daily modified SOFA score in the intensive care unit (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; range score 0-20).
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Until ICU discharge, maximun 90 days after randomization
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Vasopressor free days
Time Frame: Until ICU discharge, maximun 90 days after randomization
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Days alive without vasopressor in the ICU within 28-and 90 days
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Until ICU discharge, maximun 90 days after randomization
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Renal replacement free days
Time Frame: Until ICU discharge, maximun 90 days after randomization
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Days without renal replacement in the ICU within 28 -and 90 days
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Until ICU discharge, maximun 90 days after randomization
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Mechanical ventilation free days
Time Frame: Until ICU discharge, maximun 90 days after randomization
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Days alive without mechanical ventilation in the ICU within 90 days
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Until ICU discharge, maximun 90 days after randomization
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Serious adverse reactions (SARs)
Time Frame: Until day 7 after randomization
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Numbers of serious adverse reactions within the first 7 days
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Until day 7 after randomization
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Serious adverse events (SAEs)
Time Frame: Until day 7 after randomization
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Numbers of serious adverse events within the first 7 days
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Until day 7 after randomization
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Anders Perner, MD, PhD, Copenhagen University Hospital, Intensive care Unit 4131
- Study Director: Pär I Johansson, MD, DMSc, Copenhagen University Hospital, Capital Blood Bank 2034
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Respiration Disorders
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- COVID-19
- Respiratory Insufficiency
- Vasodilator Agents
- Platelet Aggregation Inhibitors
- Iloprost
Other Study ID Numbers
- COMBAT-COVID-19
- 2020-001296-33 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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