Clinical trial NCT04691089: Cardiopulmonary Resuscitation Performance of Professional Rescuers With a New Defibrillation Algorithm
Official title: Professional Rescuers Cardiopulmonary Resuscitation Performance After Implementation of a Defibrillation Algorithm for Early Treatment of Refibrillation, an Observational Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiac Arrest, Sudden
Ventricular Tachycardia
Ventricular Fibrillation
Sudden Cardiac Death
Keywords: Cardiac Arrest
Automatic External Defibrillator
Chest Compression Fraction
Electrical Cardiac Analysis under Chest Compressions
Lead sponsor: French Defence Health Service
Sponsor class: OTHER_GOV
First posted: 2020-12-31
Enrollment: 285
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Medical OHCA patients of the greater Paris (Paris, Haut-de-Seine, Seine-Saint-Denis and Val- de-Marne Country)

Brief summary: In the Paris (France) Medical Emergency system, in the early phase of Out-of-hospital Cardiac Arrest (OHCA), the treatment of a Ventricular Fibrillation (VF) consists of delivering an External Electric Shock (EES) by a rescuer with the use of an Automated External Defibrillator (AED). This latter realizes a cardiac rhythm analysis every two minutes. This analysis requires that chest compressions (CC) be interrupted for a while. However, CC interruptions are potentially harmful due to the brain, and heart perfusions decrease.

On the other hand, the recurrence of VF occurs mostly during the first minute after the shock, whereas the delay between 2 rhythm analysis is 2 minutes. The consequence is excessive time spent in VF, which is deleterious in terms of coronary and cerebral perfusion.

The investigator implements a new AED algorithm whose operating principle is as follows. One minute after an EES administration, the AED realizes a cardiac rhythm analysis during which the rescuers do not need to interrupt the chest compressions (CC): this is called the rhythm analysis " in presence of CC" The detection of a VF " in presence of CC " needs to be confirmed, " in absence of CC " The CC's are therefore interrupted for new rhythm analysis. Once the presence of VF is approved, the AED proposes a shock to be administred

The aim of the study

Study Design:

This is a prospective observational study.

The eligibility criteria are as follows:

* Patients in Out-Of-Hospital Cardiac Arrest.
* Basic Life support care with an AED.

The primary endpoint is the " chest-compression fraction (CCF) " that represents the CPR-time performance during the ten first minutes of BLS care ( or \< 10 min in case of Return Of Spontaneus Circulation (ROSC))

Detailed description: BACKGROUND

For Out-Of-Hospital Cardiac Arrest (OHCA) patients suffering from ventricular fibrillation (VF) or ventricular tachycardia (VT), BLS care consists of administering external electric shocks (EES) and cardiopulmonary resuscitation (CPR). However, despite successful defibrillation, VF recurs in 50% of cases. Rescuers are forced to repeat EES as often as needed, without the recommendations specifying a maximum number.

International guidelines recommend a 2-min CPR time between 2 rhythm analysis, that means one shock every 2 min. Since refibrillation occurs mostly during the first-minute post-shock, the patient will have to wait until the end of the 2 minutes before receiving the next EES. During that time, the chest compressions (CC) provide a reduced fraction of physiologic blood flow.

The new AED algorithm provides the following changes :

* After a 60-second post-shock CPR-period, the AED performs an analysis "in presence of CC" i.e., without CC interruption is performed.
* Each time the AED detects a VF "in presence of CC" the algorithm requires the CC to be interrupted to perform an analysis "in absence of CC " to confirm the rhythm shockability.
* Analyses "in presence of CC" are triggered every minute, possibly followed or not by an analysis " in absence of CC "
* at least, the algorithm performs an analysis " in absence of CC " systematically every 2 minutes.

This new algorithm fits in between two historical CPR algorithms used in western medical systems - the one-minute and the two-minute CPR cycle- depending on the rhythm shockability detected " in presence of CC "

OBJECTIVES

The main objective is to measure the " CC fraction " during the ten first minutes of Fire Fighter BLS care in OHCA.

The secondary objectives :

1. Report on the available CPR quality parameters (CC frequency, hands-off maximum).
2. Report on the AED's diagnostic performance when analyzing the rhythm "in presence of CC "
3. Report on the AED's diagnostic performance when analyzing the rhythm " in absence of CC "
4. Report on the overall AED's diagnostic performance that results from the combination of two consecutive analyses " in presence of CC " and " in absence of CC"
5. Report on post-shock rhythms and their incidence
6. Report on the number of EES per patient
7. Report on the time distribution for the shocks administered per-patient to describe the rhythmic storm.
8. Report on the incidence of Return Of Spontaneous Circulation (ROSC), survival at hospital admission, and survival at hospital discharge.
9. Compare these reports to a historical cohort (2017).

METHOD

This is a prospective observational study.

* The observation window is limited to CPR cycles within the first 10 minutes of BLS care, or less if ROSC is presumed.
* The choice of 10 minutes is intended to observe the BLS team's action, without interfering with the ALS team that arrives later.
* The three following criteria define a presumptive ROSC:
* 1. presence of QRS complexes of broadly similar morphology
* 2. synchronous impedance curve variation with the QRS complexes (indicating intrathoracic movement, in that case, cardiac mechanical activity)
* 3. no on-going CC
* A CPR cycle is defined by the delay between two " in absence of CC " analyses.

The study does not imply any change in current practice. There is no planned interim analysis.

All consecutive participants with inclusion criteria and no exclusion criteria will be analyzed.

STUDY SIZE

The sample size was calculated to perform a non-inferiority analysis first, followed by a superiority test if non-inferiority was demonstrated.

Non-inferiority test. The formula for calculating the required sample size in each group is based on a well-established statistical methodology designed for comparing two means in the context of a non-inferiority test.

n = ((Z α/2 + Z β)2 X (σ12 + σ22)) / (μ1- μ2 - δ)2

With:

* Sample size (n): the number of subjects required in each group.
* α risk: Initially set at 0.025, this value is adjusted to account for multiple hypothesis testing by applying the Bonferroni correction.
* Power 1- β: Established at 90%
* Expected mean difference: This value is set to zero for this study.
* σ (Standard Deviation): The value for each group has been set to 17.
* δ (Non-Inferiority Margin): This margin is set at 5, an arbitrary value considered the maximal loss of effect (inferiority) that would be clinically acceptable when comparing CCF 2021 with CCF 2017

After the calculations, the required sample size was 208 subjects for each group involved in the non-inferiority testing.

Superiority test. Should the non-inferiority hypothesis not be rejected, the study design allows for a subsequent superiority test to be conducted.

For superiority, the investigators use the formula :

n = ((Z α/2 + Z β)2 X (σ12 + σ22)) / (μ1- μ2)2

With:

* Z α/2 : the Z value for an alpha/2 significance level
* Z β : the Z value for a 1-beta power
* σ12 and σ22 : the variances of the two groups
* μ1 and μ2 : the means of the two groups.

For α risk = 0.025 (Bonferroni correction), a power established at 90%, a standard deviation of 17, and a detectable difference between the two groups of 5%, the required sample size was 256 subjects for each group involved in the superiority testing. (STATA : sampsi 65 70 ,SD(17) alpha(0.025)) To account for a 10% loss of subjects, the number of patients was increased to 282, rounded up to 285 per group, i.e., a total of 570 patients.

To observe 285 shockable patients, the investigators estimate the observation time required to be one year.

Note that this same number of patients will be sufficient to detect an absolute 10% difference with an alpha risk of 5% and a power of 90%, between patients in the "2017" group and patients in the "2020" group with regard to the secondary endpoint "Survival at hospital admission"

INTERRUPTION OR STOPPING OF THE STUDY

The sponsor has the responsibility to report, to the national health authority, any serious and unexpected adverse events attributable to the new AED algorithm.

RISKS

A full report on the risks, the description of incidents, accidents and adverse events will be the subject of a chapter in the results section and also in the discussion.

FINANCING

Funding for the study is provided by the Paris Fire Brigade (promoter, following acceptance of the survey under French policy for clinical research projects)

DISCUSSION

The study will report on the CC fraction of an AED algorithm designed to analyze "under CC."

Eligibility criteria: Inclusion Criteria:

-Non-traumatic OHCA in adults, treated by a BLS team and connected to an AED equipped either with the 2017 or with the 2020 algorithm.

Exclusion Criteria:

* Use of AED in a pediatric mode
* CPR administered in 15:2 mode
* Patient already connected to another defibrillator at the arrival of the BLS Team
* No shock advised by defibrillator at first analysis
* Patient with a pacemaker

Secondary Exclusion Criteria

* Surviving patients' opposition to the use of their data.
* Patients with unreadable electrocardiographic or impedance data.

Primary outcomes:
measure: Report on Chest Compression Fraction (CCf)
timeFrame: 10 minutes
Secondary outcomes:
measure: Report on Cardiopulmonary Resuscitation (CPR) parameters : CPR ratio
timeFrame: 10 minutes
measure: Report on Cardiopulmonary Resuscitation (CPR) parameters :Prompt CPR fraction
timeFrame: 10 minutes
measure: Report on Cardiopulmonary Resuscitation (CPR) parameters:Maximal Hands-Off time
timeFrame: 10 minutes
measure: Report on Cardiopulmonary Resuscitation (CPR) parameters:Chest Compression Frequency
timeFrame: 10 minutes
measure: Report on the diagnostic performance of the AED algorithms "during CC" and " in absence of CC"
timeFrame: 10 minutes
measure: Report on the overall diagnostic performance resulting from the combination of the consecutive analyses " in presence of CC " and " in absence of CC"
timeFrame: 10 minutes
measure: Report on five-second-post-shock rhythms and their incidence
timeFrame: 10 minutes
measure: Report on 60-second-post-shock rhythms and their incidence
timeFrame: 10 minutes
measure: Report on 120 second-post-shock rhythms and their incidence
timeFrame: 10 minutes
measure: Report on 15-second-post-shock rhythms and their incidence
timeFrame: 10 minutes
measure: Report on 30-second-post-shock rhythms and their incidence
timeFrame: 10 minutes
measure: Report on the number of electrical shocks (EES) delivered and the duration of the rhythmic storm
timeFrame: 1 hour
measure: Report on the number of electrical shocks (EES) intended and the duration of the rhythmic storm
timeFrame: 1 hour
measure: Report on the temporal distribution of electrical shocks (EES) and the duration of the rhythmic storm
timeFrame: 1 hour
measure: Report on the delay from start to end of cumulative VF episodes
timeFrame: 1 hour
measure: The time period from the AED-switch-on and the first EES (describe in seconds)
timeFrame: 1 hour
measure: The distribution over time of EES.
timeFrame: 1 hour
measure: Outcomes - ROSC
timeFrame: 2 hours
measure: Outcomes - admitted alive at hospital
timeFrame: 2 hours
measure: Outcomes - discharged from hospital
timeFrame: 1 month
measure: Compare Chest Compression Fraction (CCf) to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Prompt CPR fraction (duration between the two AED announcements "resume massage" and "interrupt massage"/ total management time; describe as a %)
timeFrame: 10 minutes
measure: CPR ratio (time during which the patient receives chest compression and bag ventilation / total management time; describe as a %)
timeFrame: 10 minutes
measure: Maximal Hands-Off time (longest time frame without any CC; describe in seconds)
timeFrame: 10 minutes
measure: Chest Compression Frequency (i.e., measurement of the mobile frequency over 3 to 5 compressions; describe as number of chest compressions by minute)
timeFrame: 10 minutes
measure: Compare Sensibility and Specificity of AED algorithm "during CC" and "in absence of CC" to 2017 algorithm Sensibility and Specificity
timeFrame: 10 minutes
measure: Compare the overall diagnostic performance resulting from the combination of the consecutive analyses " in presence of CC " and " in absence of CC" to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Compare post-shock rhythms and their incidence to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Compare post-shock rhythms and their incidence to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Compare post-shock rhythms and their incidence to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Compare post-shock rhythms and their incidence to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Compare number of electrical shocks (EES) and the duration of the rhythmic storm to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Compare number of electrical shocks (EES) and the duration of the rhythmic storm to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Compare number of electrical shocks (EES) and the duration of the rhythmic storm to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Compare number of electrical shocks (EES) and the duration of the rhythmic storm to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Compare number of electrical shocks (EES) and the duration of the rhythmic storm to Paris Fire Brigade 2017 historical data
timeFrame: 10 minutes
measure: Outcomes - ROSC
timeFrame: 1 hour
measure: Outcomes - admitted alive at hospital
timeFrame: 2 hours
measure: Outcomes - hospital discharge
timeFrame: 1 month
Other outcomes:
Locations:
city: Paris
country: France
facility: Paris Fire Brigade
state: Non, Merci
Study officials:
affiliation: Paris Fire Brigade
name: Clément DERKENNE, MD
role: PRINCIPAL_INVESTIGATOR
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