Infusion of Prostacyclin (Iloprost) vs Placebo for 72-hours in Patients With Septic Shock Suffering From Organ Failure

NCT04123444 | Completed Phase 2 DMC

• 2 other identifiers: COMBAT-SHINE2019-001131-31
• Study Type: interventional
• Target: 279
• Locations: 1 country
• Sites: 6

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 up to a total of 380 patients with septic shock suffering from organ 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 septic shock patients suffering from organ failure caused by endothelial breakdown, ultimately improving survival.

Conditions

Septic Shock

Outcome Measures

Primary Outcomes (1)

• Modified Sequential Organ Failure Assessment (SOFA)

  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).

  Up to 90 days after randomization

Secondary Outcomes (6)

• 28 and 90-day mortality

  Day 28 and 90 after randomization

• Vasopressor free days

  Until ICU discharge, maximun 90 days after randomization

• Mechanical ventilation free days

  Until ICU discharge, maximun 90 days after randomization

• Renal replacement 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=190 patients) will receive continuous infusion of iloprost for 72 hours after inclusion or until discharge to ward or death, whichever comes first.

Drug: Iloprost

Placebo

PLACEBO COMPARATOR

Patients randomized to placebo treatment (n=190 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. treatment dose 1 ng/kg/min

Also known as: Iloprost infusion

Iloprost

Isotonic saline DRUG

Continuously infusion for 72 hours.

Also known as: Isotonic saline infusion

Placebo

Eligibility Criteria

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

You may qualify if:

• All the following criteria must be fulfilled:
• Adult intensive care patients (age ≥ 18 years)
• Septic shock defined according to the Sepsis-3 criteria:
• suspected or documented infection
• persisting hypotension requiring vasopressors to maintain a mean arterial blood pressure of 65 mmHg or above
• Lactate level of 2 mmol/L or above despite fluid therapy within the last 3 hours at screening
• Soluble thrombomodulin (sTM) above 10 ng/mL

You may not qualify if:

• Patients who fulfil any of the following criteria will be excluded:
• Withdrawal from active therapy
• Pregnancy
• Known hypersensitivity to iloprost.
• Life-threatening bleeding as defined by the treating physician
• Known severe heart failure (New York Heart Association (NYHA) class IV)
• Suspected acute coronary syndrome
• Previously included in this trial
• Septic shock for more than 12 hours at the time of screening
• Informed consent cannot be obtained
• Included in other clinical trials with prostacyclin within 90 days

Sponsors & Collaborators

• Jakob Stensballe, MD, PhD: lead
• Innovation Fund Denmark: collaborator
• Independent Research Fund Denmark: collaborator

Study Sites (6)

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

Region Sealand University Hospital

Køge, Denmark

Location

Related Publications (2)

• Bestle MH, Stensballe J, Lange T, Clausen NE, Soe-Jensen P, Pedersen KH, Gybel-Brask M, Kjaer MN, Steensen CO, Jensen DB, Gartner R, Schonemann-Lund M, Kristiansen KT, Lindhardt A, Johansson PI, Perner A. Iloprost and Organ Dysfunction in Adults With Septic Shock and Endotheliopathy: A Randomized Clinical Trial. JAMA Netw Open. 2024 Sep 3;7(9):e2432444. doi: 10.1001/jamanetworkopen.2024.32444.

  PMID: 39259541 DERIVED

• Bestle MH, Clausen NE, Soe-Jensen P, Kristiansen KT, Lange T, Johansson PI, Stensballe J, Perner A. Efficacy and safety of iloprost in patients with septic shock-induced endotheliopathy-Protocol for the multicenter randomized, placebo-controlled, blinded, investigator-initiated trial. Acta Anaesthesiol Scand. 2020 May;64(5):705-711. doi: 10.1111/aas.13546. Epub 2020 Feb 3.

  PMID: 31950481 DERIVED

MeSH Terms

Conditions

Shock, Septic

Interventions

Iloprost; Sodium Chloride

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

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

• Morten Bestle, MD, PhD

  Nordsjaelands Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patient, investigator, outcome assessor and care provider will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor

Model Details: Randomization in 2 parallel arms Adaptive phase 2b/3 trial

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 11, 2019
• Study Start: October 30, 2019
• Primary Completion: June 28, 2022
• Study Completion: June 28, 2022
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (6)