Impact of low dose epinephrine in the management of out-of-hospital cardiac arrest on neurological outcome: A multicenter randomized and double-blind trial (Low-EPI Study)

2023-505349-26-00 Protocol 2021PI170 Therapeutic confirmatory (Phase III) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 26 sites · Protocol 2021PI170

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Authorised, recruitment pending
Participants planned 4,336
Countries 1
Sites 26

Out-of-hospital cardiac arrest.

To evaluate the impact of a low dose of epinephrine (0.5 mg bolus) versus the standard dose (1 mg bolus) of epinephrine on 28-day survival with a favorable neurological outcome in patients with out-of-hospital cardiac arrest (OHCA) managed by a Mobile Medical Team (MMT).

Key facts

Sponsor
CHRU De Nancy
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Decision date (initial)
2025-10-08
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
French Ministry of Health (PHRC-N)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To evaluate the impact of a low dose of epinephrine (0.5 mg bolus) versus the standard dose (1 mg bolus) of epinephrine on 28-day survival with a favorable neurological outcome in patients with out-of-hospital cardiac arrest (OHCA) managed by a Mobile Medical Team (MMT).

Secondary objectives 1

  1. The secondary objectives are to compare the following outcomes between patients who receive the standard dose (1 mg bolus) of epinephrine and those who receive a low dose of epinephrine (0.5 mg bolus): • Return of spontaneous circulation (ROSC). • Survival at hospital admission. • 28-day survival. • 28-day neurological outcome as evaluated by the Modified Rankin Scale (mRS) score

Conditions and MedDRA coding

Out-of-hospital cardiac arrest.

VersionLevelCodeTermSystem organ class
20.0 PT 10007515 Cardiac arrest 100000004849

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Main treatment and follow-up period
Randomized treatment during out-of-hospital resuscitation followed by 28-day follow-up to assess survival and neurological outcome
 Randomised Controlled Double [{"id":170478,"code":3,"name":"Monitor"},{"id":170477,"code":1,"name":"Subject"},{"id":170480,"code":4,"name":"Analyst"},{"id":170479,"code":2,"name":"Investigator"},{"id":170476,"code":5,"name":"Carer"}] Standard dose: 1 mg epinephrine IV bolus every 3–5 minutes during CardioPulmonary Resuscitation (CPR).
Low dose: 0.5 mg epinephrine IV bolus every 3–5 minutes during CardioPulmonary Resuscitation (CPR)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. Male or female, aged ≥18 years.
  2. Out-of-hospital cardiac arrest for which resuscitation is decided by the SMUR team.
  3. Medical Out-of-hospital cardiac arrest.
  4. Affiliated with or beneficiary of a social security plan

Exclusion criteria 3

  1. Non-medical OHCA (traumatic, drownings, electrocution, asphyxia, overdose, unknown cause).
  2. out-of-hospital cardiac arrest without advanced life support (Do Not Attempt Resuscitation order, body finding, the decision not to attempt ALS is at the physician’s discretion).
  3. Individuals referred to in Articles 10, 31, 32, 33 and 34 of Regulation (EU) No 536/2014, including. ­ Pregnant women, birthing or breastfeeding mothers ­ Adults under legal protection measure (such as guardianship, conservatorship) ­ Individuals deprived of liberty due to judicial or administrative decision

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. 28-day survival with a favorable neurological function defined as a Modified Rankin Scale (mRS) of score 2 or less at 28-days.

Secondary endpoints 1

  1. The secondary endpoints are: • Return of Spontaneous Circulation, assessed during cardiopulmonary resuscitation (CPR) and defined as a clinical assessment that shows signs of life, including palpable pulse or generating a blood pressure. • Survival at hospital admission. • 28-day survival. • Modified Rankin Scale (mRS) score used as a continuous variable (in contrast with the use of the mRS scale in the primary outcome).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

ADRENALINE RENAUDIN 0,50 mg/ml, solution injectable

PRD2894039 · Product

Active substance
Epinephrine Bitartrate
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS BOLUS INJECTION/IV INFUSION
Max daily dose
5 mg milligram(s)
Max total dose
5 mg milligram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
C01CA24 — EPINEPHRINE
Marketing authorisation
34009 364 336 5 6
MA holder
LABORATOIRE RENAUDIN
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
blind external packaging and blind labeling for clinical trial

Comparator 1

ADRENALINE RENAUDIN 1 mg/ml, solution injectable en ampoule

PRD2895851 · Product

Active substance
Epinephrine Bitartrate
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS BOLUS USE
Max daily dose
10 mg milligram(s)
Max total dose
10 mg milligram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
C01CA24 — EPINEPHRINE
Marketing authorisation
34009 565 454 5 2
MA holder
LABORATOIRE RENAUDIN
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
blind external packaging and blind labeling for clinical trial

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHRU De Nancy

18 Total trials 13 Recruiting 3 Ended
Academic / Non-commercial
Sponsor organisation
CHRU De Nancy
Address
Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Bp 60034 29 Avenue Du Mal De Lattre De Tassigny Bp 60034
City
Nancy Cedex
Postcode
54035
Country
France

Scientific contact point

Organisation
CHRU De Nancy
Contact name
Tahar CHOUIHED

Public contact point

Organisation
CHRU De Nancy
Contact name
Tahar CHOUIHED

Locations

1 EU/EEA country · 26 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Authorised, recruitment pending 4,336 26
Rest of world — 0 —

Investigational sites

France

26 sites · Authorised, recruitment pending
Centre Hospitalier Universitaire De Toulouse
CHU PURPAN / SAMU 31-, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
Centre hospitalier Annecy Genevois Site Julien en GENEVOIS
SMUR, Chemin du Loup, BP 14110,, Saint-Julien-en-Genevois
Centre Hospitalier Universitaire De Montpellier
SAMU – SMUR CHU Lapeyronie, 191 Avenue Du Doyen Gaston Giraud, 34295, Montpellier Cedex 5
CHU Besancon
Médecine d'urgence et de réanimation, 3 Boulevard Alexander Fleming, Cs 81816, Besancon Cedex
Centre Hospitalier Universitaire De Poitiers
Service Urgences SAMU SMUR 86, 2 Rue De La Miletrie, 86000, Poitiers
Centre Hospitalier Annecy Genevois
SMUR, 1 Avenue De L Hopital, Bp 90074, Epagny Metz Tessy
CHRU De Nancy
Samu - Smur - Service des Urgences, 29 Avenue Du Mal De Lattre De Tassigny, 54000, Nancy
Hopital Beaujon
SMUR, 100 Boulevard Du General Leclerc, 92110, Clichy
Centre Hospitalier De Colmar
Pôle Urgence Pasteur, 39 Avenue De La Liberte, Bp 60535, Colmar Cedex
Assistance Publique Hopitaux De Paris
Urgences, 2 Rue Ambroise Pare, 75010, Paris
Brigade de Sapeurs-Pompiers de Paris
Division Santé, 12 Rue Henri Regnault, 92400, COURBEVOIE
CH SUD Francilien
SAMU-SMUR 91, 40 avenue Serge Dassault, 91100, Corbeil-Essonnes
Centre Hospitalier Universitaire De Nice
Département hospitalo-universitaire de médecine d’urgence DHUMU, 30 Voie Romaine, 06000, Nice
Centre Hospitalier Regional Et Universitaire De Brest
Urgences, Boulevard Tanguy Prigent, 29200, Brest
Centre Hospitalier Universitaire De Nimes
Service des urgences, SMUR, 4 Place Du Professeur Robert Debre, Bp 40026, Nimes Cedex 9
Centre Hospitalier Universitaire De Rennes
Urgences-SAMU35-SAS-SMUR-CESU, 2 Rue Henri Le Guilloux, 35000, Rennes
Centre Hospitalier Universitaire De Nantes
Département des urgences SAMU, 7 Quai Moncousu, 44000, Nantes
Hopital Necker Enfants Malades
SAMU de Paris – SMUR de NECKER, 149 Rue De Sevres, 75015, Paris
Centre Hospitalier Universitaire Grenoble Alpes
SAMU 38, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9
Hospices Civils De Lyon
SAMU/ SAU, 5 Place D Arsonval, 69437, Lyon Cedex 03
Centre Hospitalier Universitaire Reims
SAU Adultes et SAMU, 45 Rue Cognacq Jay, 51092, Reims Cedex
Assistance Publique Hopitaux De Paris
SAMU 92 – SMUR Raymond Poincaré, Garches, 104 Boulevard Raymond Poincare, 92380, Garches
Centre Hospitalier De La Cote Basque
Urgences / SAMU/ SMUR, 13 Avenue Interne Jacques Loeb, 64100, Bayonne
Assistance Publique Hopitaux De Paris
Urgences générales, 43 Boulevard De L Hopital, 75013, Paris
Centre Hospitalier Universitaire Rouen
Département de médecine d'urgence, 1 Rue De Germont, Bp 96031, Rouen Cedex
Centre Hospitalier Regional Universitaire De Tours
Département des urgences, 2 Boulevard Tonnelle, 37000, Tours

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2023-505349-26-00 2.0
Recruitment arrangements (for publication) K_Recruitment arrangements_2023-505349-26-00 1.2
Subject information and informed consent form (for publication) L1_ICF_patient_Poursuite 1.2
Subject information and informed consent form (for publication) L1_SIS_Commun_Poursuite 2.0
Subject information and informed consent form (for publication) L1_SIS_Commun_suivi termine 2.0
Subject information and informed consent form (for publication) L1_SIS_Information adaptee sequelles_CE_Poursuite 2.0
Subject information and informed consent form (for publication) L1_SIS_Information adaptee sequelles_Opposition_Suivi termine 2.1
Subject information and informed consent form (for publication) L1_SIS_Patient decede 2.1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC_Adrenaline 0_5mg 1.0
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC_Adrenaline 1mg 1
Synopsis of the protocol (for publication) D1_Protocole synopsis_Fr_2023-505349-26-00 2.0

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-07-09 France Acceptable
2025-10-06
 2025-10-08
2 SUBSTANTIAL MODIFICATION SM-1 2026-03-02 France Acceptable
2026-03-27
 2026-05-20

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