The OSIRIS ECPR Trial (OSIRIS)

Out-of-hospital Refractory Cardiac Arrest Treated with Extracorporeal Cardiopulmonary Resuscitation

The OSIRIS trial is an investigator-initiated, multicenter, multinational, open-label, randomized controlled trial with a 2:1 concealed allocation of refractory out-of-hospital cardiac arrest (OHCA) patients to the extracorporeal cardiopulmonary resuscitation (ECPR) based approach versus the conventional cardiopulmonary resuscitation (CCPR) approach.

Study Overview

• Status: Not yet recruiting
• Conditions: Extracorporeal Membrane Oxygenation; Ventricular Fibrillation; Cardiac Arrest; Out-Of-Hospital Cardiac Arrest; Sudden Cardiac Arrest; Extracorporeal Cardiopulmonary Resuscitation
• Intervention / Treatment: Procedure: Extracorporeal cardiopulmonary resuscitation based approach; Procedure: Conventional cardiopulmonary resuscitation

Detailed Description

ECPR for OHCA is a resource-intensive method and poses significant challenges for both prehospital and hospital systems. Recent meta-analyses have highlighted persisting uncertainties regarding the routine use of ECPR strategy for OHCA, emphasizing the need for further research.

The refractory OHCA trial is a multicenter, multinational, open-label, randomized trial with a 2:1 concealed allocation of refractory OHCA patients to ECPR-based approach versus CCPR approach.

ECPR-based approach is defined as advanced cardiac life support (ACLS) per current guidelines with aim to proceed to in-hospital or out-of-hospital veno-arterial extracorporeal membrane oxygenation (V-A ECMO) if (return of spontaneous circulation) ROSC is not achieved before the cannulation.

CCPR is defined as conventional ACLS per current guidelines without mechanical circulatory support (MCS) use until sustained ROSC is achieved or the patient pronounced dead.

This study was designed to test the hypothesis that invasive, ECPR-based approach when compared to CCPR:

1. increases survival in selected adults with refractory OHCA.
2. and can be successfully implemented in different cities and countries.

The study will include adults 18-70 years of age suffering refractory OHCA of presumed cardiac cause. Refractory OHCA is characterized as either 3 unsuccessful defibrillations in ongoing shockable rhythms or 10 minutes of ACLS without ROSC in the case of a non-shockable rhythm following the first or second defibrillation.

• Study Type: Interventional
• Enrollment (Estimated): 686
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jan Belohlavek, MD, PhD; Phone Number: +420724371594; Email: jan.belohlavek@vfn.cz
• Study Contact Backup: Name: Daniel Rob, MD, PhD; Phone Number: +420721932067; Email: daniel.rob@vfn.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 and ≤ 70 years presumed or known
2. Witnessed OHCA
3. Bystander CPR provided
4. Presumed cardiac or unknown cause
5. An initial documented shockable rhythm of VF (ventricular fibrillation) or pulseless VT (ventricular tachycardia)
6. Minimum of ≥ 10 min of ACLS without ROSC or at least ≥ 3 defibrillations in ongoing VF/pulseless VT
7. Body morphology able to accommodate a mechanical chest compression device
8. ECPR team and intensive care unit (ICU) capacity in the receiving center available
9. Estimated transfer time from the scene to the hospital ≤ 30 minutes or to the scene ≤ 30 minutes
10. Eligible for intensive care without restrictions or limitations

Exclusion Criteria:

1. ACLS ≥ 30 minutes before randomization
2. Known limitations in care or a Do Not Attempt to Resuscitate (DNAR) order
3. Known severe disease making 90-day survival unlikely
4. Known bleeding diathesis or acute or recent intracranial bleeding
5. Known, obvious or suspected pregnancy
6. Known pre-arrest severe cognitive dysfunction (mRS ≥ 4)
7. Known hypothermia as a cause of cardiac arrest

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ECPR-based; ECPR-based approach is defined as advanced cardiac life support (ACLS) per current guidelines with aim to proceed to in-hospital or out-of-hospital veno-arterial extracorporeal membrane oxygenation (V-A ECMO) if return of spontaneous circulation (ROSC) is not achieved before the cannulation.	Procedure: Extracorporeal cardiopulmonary resuscitation based approach; ECPR-based approach is defined as ACLS per current guidelines with aim to proceed to in-hospital or out-of-hospital V-A ECMO if ROSC is not achieved before the cannulation.; Other Names: ECPR-based approach
Active Comparator: CCPR; CCPR is defined as conventional advanced cardiac life support (ACLS) per current guidelines without mechanical circulatory support (MCS) use until sustained return of spontaneous circulation (ROSC) is achieved or the patient pronounced dead.	Procedure: Conventional cardiopulmonary resuscitation; CCPR is defined as conventional ACLS per current guidelines without MCS use until sustained ROSC is achieved or the patient pronounced dead.; Other Names: CCPR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day survival	90-day survival	90-days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day neurological outcome	90-day neurological outcome measured using the modified Rankin Scale (mRS-scale) (mRS 0-3 indicating a good outcome, and mRS 4-6 indicating a poor outcome)	90-days
90-day Health-related quality of life	90-day Health-related quality of life (HRQoL) using EuroQol 5-Dimension 5-Level (EQ5D-5L)	90-days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival to discharge	Survival to hospital discharge for the index event	up to 90-days
30-day survival	30-day survival	30-days
Neurological outcome at discharge	Neurological outcome at discharge from index hospitalization (mRS 0-3 indicating a good outcome, and mRS 4-6 indicating a poor outcome)	up to 90-days
Neurological outcome at 30 days	Neurological outcome at 30 days (mRS 0-3 indicating a good outcome, and mRS 4-6 indicating a poor outcome)	30-days
Neurological outcome at 30 days or discharge	Neurological outcome at 30 days or discharge whatever comes first measured using the mRS scale (mRS 0-3 good outcome, mRS 4-6 poor outcome)	discharge date or 30-days
Win ratio	Win ratio (Dead vs alive, all steps on the mRS-scale, safety event, HRQoL)	up to 90-days
Potential organ donor	Number of participants fulfilling criteria of donor after brain death (DBD) or donor after circulatory death (DCD))	up to 90-days
Accepted organ donor	Number of participants with DBD or DCD who met the established medical, legal, and ethical criteria for organ donation and whose organs were harvested for transplantation.	up to 90-days
Additional mechanical circulatory support (MCS) implantation	Additional mechanical circulatory support (MCS) implantation (any MCS use in the standard arm or additional MCS implantation to ECMO in the intervention arm)	up to 90-days
Best neurological outcome at any time within 90 days (mRS scale)	Best neurological outcome at any time within 90 days, assessed using the mRS scale (mRS 0-3 indicating a favorable outcome and mRS 4-6 indicating an unfavorable outcome).	up to 90-days
Cardiovascular mortality at 90 days	Mortality due to myocardial infarction, heart failure, cardiogenic shock, cardiac arrhytmia, rearrest, ischemic stroke	90-days
Major Adverse Cardiovascular Events (MACE) at 90 days	MACE include CV death, nonfatal MI, stroke, resuscitated cardiac arrest	90-days

Collaborators and Investigators

• Sponsor: General University Hospital, Prague
• Collaborators: Karolinska Institutet; Medical University of Vienna; Aarhus University Hospital; Heinrich-Heine University, Duesseldorf; Ludwig-Maximilians - University of Munich; University of London; Royal Brompton & Harefield NHS Foundation Trust; University Hospital, Zürich; University Hospital Freiburg; University Medical Centre Ljubljana; Heart Center Leipzig - University Hospital; Masaryk University; Hospital Vall d'Hebron; Region Hovedstadens Apotek; European Clinical Research Infrastructure Network; Insel Gruppe AG, University Hospital Bern; Uniwersytet Wrocławski
• Investigators: Principal Investigator: Jan Bělohlávek, MD, PhD, General University Hospital, Prague

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: January 30, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 30, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: cardiac arrest; out-of-hospital cardiac arrest; extracorporeal membrane oxygenation; extracorporeal cardiopulmonary resuscitation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Death; Death, Sudden; Heart Arrest; Death, Sudden, Cardiac; Out-of-Hospital Cardiac Arrest; Ventricular Fibrillation
• Other Study ID Numbers: 442024-41/24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No