Clinical trial NCT06939335: The Application of Positive End-Expiratory Pressure in Out-of-Hospital Cardiac Arrest: The Lazarus-PEEP Trial.
Official title: The Application of Positive End-Expiratory Pressure in Out-of-Hospital Cardiac Arrest: The Lazarus-PEEP Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cardiac Arrest (CA)
Out-of-hospital Cardiac Arrest (OHCA)
Positive End-expiratory Pressure (PEEP)
Ventilation During Resuscitation
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2025-04-22
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter parallel controlled randomised clinical trial
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Return of spontaneous circulation (ROSC)
timeFrame: Day one
Secondary outcomes:
measure: Survival to hospital admission
timeFrame: Day one
measure: Survival to hospital discharge
timeFrame: From enrolment until hospital discharge or death - whichever happens first. Average hospitalisation after OHCA is 24 days.
measure: 30-day survival
timeFrame: From enrollment to the end of 30 days.
measure: 90-day survival
timeFrame: From enrollment to the end of 90 days.
measure: Neurological outcome at discharge
timeFrame: From enrolment until hospital discharge or death - whichever happens first. Average hospitalisation after OHCA is 24 days.
Other outcomes:
measure: Airflow during ventilation
timeFrame: Periprocedural
measure: Airway pressure during ventilation
timeFrame: Periprocedural
measure: Occurence of potential adverse effects
timeFrame: Day one
measure: Capnography
timeFrame: Periprocedural
measure: Compression depth
timeFrame: Periprocedural
measure: Compression frequency
timeFrame: Periprocedural
Locations:
city: Aalst
country: Belgium
facility: AZORG: campus Merestraat
city: Aalst
country: Belgium
facility: AZORG: Campus Moorselbaan
city: Geraardsbergen
country: Belgium
facility: AZORG: campus Geraardsbergen
city: Ghent
country: Belgium
facility: UZ Ghent
city: Knokke
country: Belgium
facility: AZ Zeno
Study officials:
affiliation: UZ Gent
name: Saïd Hachimi Idrissi, MD, PhD, Professor
role: PRINCIPAL_INVESTIGATOR
References: