The Application of Positive End-Expiratory Pressure in Out-of-Hospital Cardiac Arrest: The Lazarus-PEEP Trial. (Lazarus-PEEP)

The goal of this clinical trial is to learn whether using Positive End-Expiratory Pressure (PEEP) during cardiopulmonary resuscitation (CPR) improves outcomes for adults who experience out-of-hospital cardiac arrest, a condition where the heart suddenly stops beating. PEEP is used during ventilation, which may enhance oxygen levels by keeping the airways open throughout CPR.

This study aims to determine if using PEEP during CPR helps restart the heart more effectively, improves survival rates, and enhances survival with good neurologic outcomes after a cardiac arrest compared to standard CPR without PEEP.

Researchers will randomly assign participants to one of two groups: one receiving CPR with PEEP set at 5 cm of water pressure and the other receiving standard CPR without PEEP. Participants will be treated by emergency medical teams trained in advanced life support, and specialised sensors will measure airflow and airway pressure during resuscitation.

Additionally, the study will evaluate potential side effects associated with PEEP, such as increased pressure within the chest or lung injuries. Findings from this trial will guide recommendations on the usage of PEEP in standard CPR practices to potentially improve patient outcomes.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Arrest (CA); Out-of-hospital Cardiac Arrest (OHCA); Positive End-expiratory Pressure (PEEP); Ventilation During Resuscitation
• Intervention / Treatment: Device: Disposable PEEP Valve set at 5 cm H20.; Device: Controle

Detailed Description

Introduction: Sudden cardiac arrest is a significant cause of mortality, with an estimated annual incidence of 84 cases per 100,000 individuals in Europe. Effective cardiopulmonary resuscitation (CPR), including proper ventilation, is crucial for survival. However, the interplay between ventilation and circulation during CPR is complex and not fully understood. While ventilation is necessary for oxygenation, excessive hyperventilation and high intrathoracic pressures can be detrimental. Positive End-Expiratory Pressure (PEEP) may improve oxygenation and ventilation by maintaining alveolar patency and improving oxygenation. Previous observational studies have suggested that PEEP might enhance the rate of Return of Spontaneous Circulation (ROSC) and improve short-term outcomes. However, no prospective randomised clinical trials have been conducted to confirm these findings. The Lazarus-PEEP trial aims to address this gap by evaluating the efficacy and safety of PEEP during CPR for out-of-hospital cardiac arrest (OHCA) patients.

Methodology: The study will be conducted at Ghent University Hospital and three non-university hospitals in Belgium, enrolling adult patients who experience non-traumatic OHCA and are intubated and ventilated during resuscitation efforts by an advanced life support (MUG) team. Participants will be randomised to receive either PEEP at 5 cm H2O or no PEEP (0 cm H2O) during CPR. Custom-built sensors will measure tracheal airflow and pressure, while additional data on CPR quality and patient outcomes will be collected. The trial's primary outcome measure is the rate of ROSC, with secondary outcomes including survival to hospital admission and discharge, as well as neurological outcomes at discharge.

Outcome: The study will evaluate the effectiveness of PEEP in improving ROSC rates, short-term survival, and neurological outcomes. Safety profiles will also be examined, focusing on adverse effects such as barotrauma and increased intrathoracic pressures. Comprehensive data collection will provide insights into the physiological impact of PEEP during CPR and its feasibility in a pre-hospital setting.

Conclusion: The Lazarus-PEEP trial aims to gather strong evidence on the potential advantages and risks of utilizing PEEP during CPR for OHCA patients. The results will inform evidence-based guidelines and enhance resuscitation practices, potentially leading to improved patient outcomes. The findings will be disseminated through influential journals, major scientific conferences, and public data-sharing platforms to ensure widespread accessibility and impact.

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Thomas Tackaert, MD; Phone Number: 0032 53 72 49 96; Email: thomas.tackaert@ugent.be

Study Locations

• Belgium
  • Aalst, Belgium, B-9300
    • Recruiting
    • AZORG: campus Merestraat
    • Contact: AZORG: campus Merestraat; Phone Number: 0032 53 76 40 06; Email: spoedopname.asz@azorg.be
    • Principal Investigator: Jolien Volcke, MD
  • Aalst, Belgium, B-9300
    • Recruiting
    • AZORG: Campus Moorselbaan
    • Contact: AZORG: Campus Moorselbaan; Phone Number: 0032 53 72 49 96
    • Principal Investigator: Thomas Tackaert, MD
  • Geraardsbergen, Belgium, B-9500
    • Recruiting
    • AZORG: campus Geraardsbergen
    • Contact: AZORG: campus Geraardsbergen; Phone Number: 0032 54 43 27 11; Email: spoedopname@azorg.be
    • Principal Investigator: Jolien Volcke, MD
  • Ghent, Belgium, B-9240
    • Recruiting
    • UZ Ghent
    • Contact: Spoedgevallendienst UZ Gent; Phone Number: 0032 9 332 50 24; Email: secretariaatspoed@uzgent.be
    • Principal Investigator: Saïd Hachimi Hachimi Idrissi, MD, PhD, Professor
    • Sub-Investigator: Tom Coucke, MD
    • Sub-Investigator: Hannah Van Belleghem, MD
    • Sub-Investigator: Sarah Ballet
  • Knokke, Belgium, 8300
    • Recruiting
    • AZ Zeno
    • Contact: Urgentiegeneeskunde - spoed AZ Zeno Knokke-Heist; Phone Number: 0032 50 535 112; Email: info@azzeno.be
    • Principal Investigator: Tom De Coninck, MD
  • West-Flandres
    • Ostend, West-Flandres, Belgium, 8400
      • Recruiting
      • AZ Oostende
      • Contact: Maxim Vanwulpen, MD, PhD; Phone Number: 0032 59 41 40 80; Email: maxim.vanwulpen@azoostende.be
      • Principal Investigator: Maxim Vanwulpen, MD, PhD
• France
  • Besançon, France
    • Active, not recruiting
    • Centre hospitalier universitaire (CHU) Besançon-Franche-Comté

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age: Adults aged 18 years and older.
2. Type of Cardiac Arrest: Patients who have experienced a non-traumatic out-of-hospital cardiac arrest.
3. CPR Administration: Patients receiving cardiopulmonary resuscitation from an advanced life support (ALS) team.
4. Intubation and Ventilation: Patients who are intubated and ventilated during resuscitation efforts.

Exclusion Criteria:

1. Cardiac arrest in patient younger than 18 years of age.
2. Traumatic cardiac arrest, including drowning, penetrating or blunt injury, and burns.
3. Immediate Return of Spontaneous Circulation (ROSC): Patients who achieve ROSC before intubation and initiation of intubation.
4. Pregnancy.
5. Mechanical ventilation during arrest: patients already receiving mechanical ventilation at the moment of cardiac arrest, due to reasons other than their arrest, will be excluded.
6. Do Not Resuscitate (DNR) Orders: Patients with existing DNR orders or any advanced directive indicating that CPR should not be performed.
7. Failure to intubate: if intubation is unsuccessful, ventilation by any means (MBV, SGA) should take priority over the study protocol, and the patient is excluded.
8. Enrolment in Other Studies: Patients currently enrolled in another interventional clinical trial that could interfere with the outcomes of this study.

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: Intervention; Ventilation during cardiac arrest with an adult Resuscitation Bag with a pressure relief valve set at 40 cm H20 and a disposable PEEP Valve set at 5 cm H20.	Device: Disposable PEEP Valve set at 5 cm H20.; Ventilation during cardiac arrest with an adult Resuscitation Bag with a pressure relief valve set at 40 cm H20 and a 22 mm disposable PEEP Valve set at 5 cm H20.
Active Comparator: Controle; Ventilation during cardiac arrest with an adult Resuscitation Bag with a pressure relief valve set at 40 cm H20 without a disposable PEEP Valve.	Device: Controle; Ventilation during cardiac arrest with an adult Resuscitation Bag with a pressure relief valve set at 40 cm H20 without a disposable PEEP Valve.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return of spontaneous circulation (ROSC)	The occurrence of Return of spontaneous circulation (ROSC), defined as the return of sustained spontaneous circulation for at least 20 minutes per ERC guidelines	Day one

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival to hospital admission		Day one
Survival to hospital discharge		From enrolment until hospital discharge or death - whichever happens first. Average hospitalisation after OHCA is 24 days.
30-day survival		From enrollment to the end of 30 days.
90-day survival		From enrollment to the end of 90 days.
Neurological outcome at discharge	Neurological outcome at discharge, as defined by the Cerebral Performance Category Scale.	From enrolment until hospital discharge or death - whichever happens first. Average hospitalisation after OHCA is 24 days.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airflow during ventilation	The Sensirion SFM3200AW flow sensor will measure airflow during cardiopulmonary resuscitation, measured in ml.	Periprocedural
Airway pressure during ventilation	The Wika CPT2500 sensor will measure airway pressure during cardiopulmonary resuscitation, measured in mbar.	Periprocedural
Occurence of potential adverse effects	The incidence of barotrauma, including pneumothorax and pneumomediastinum	Day one
Capnography	the ZOLL® X Series® monitor-defibrillator will be used to collect capnography data during cardiopulmonary resuscitation, measured in mmHg.	Periprocedural
Compression depth	The ZOLL® X Series® monitor-defibrillator will be used to measure Compression depth, measured in mm.	Periprocedural
Compression frequency	The ZOLL® X Series® monitor-defibrillator will be used to measure Compression frequency, measured in compressions/minute.	Periprocedural

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Saïd Hachimi Idrissi, MD, PhD, Professor, UZ Gent

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: March 31, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: ONZ-2024-0496

Plan for Individual participant data (IPD)

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

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