Clinical trial • Phase III • Cardiology
Epinephrine bitartrate for Out-of-hospital cardiac arrest | Cardiac arrest
Phase III trial of Epinephrine bitartrate for Out-of-hospital cardiac arrest | Cardiac arrest.
Overview
- Trial Therapeutic Area
- Cardiology
- Trial Disease
- Out-of-hospital cardiac arrest | Cardiac arrest
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 09-07-2025
- First CTIS Authorization Date
- 08-10-2025
Trial design
Randomised, standard dose arm: adrenaline renaudin 1 mg/ml, solution injectable en ampoule — 1 mg epinephrine iv bolus every 3–5 minutes during cardiopulmonary resuscitation (cpr). test arm (low dose): adrenaline renaudin 0,50 mg/ml, solution injectable — 0.5 mg epinephrine iv bolus every 3–5 minutes during cpr.-controlled Phase III trial across 26 sites in France.
- Randomised
- Yes
- Comparator
- Standard dose arm: ADRENALINE RENAUDIN 1 mg/ml, solution injectable en ampoule — 1 mg epinephrine IV bolus every 3–5 minutes during cardiopulmonary resuscitation (CPR). Test arm (low dose): ADRENALINE RENAUDIN 0,50 mg/ml, solution injectable — 0.5 mg epinephrine IV bolus every 3–5 minutes during CPR.
- Target Sample Size
- 4336
- Trial Duration For Participant
- 28
Stratification factors
- SMUR vehicle
Eligibility
Recruits 4336 Vulnerable populations are explicitly considered and partly excluded: the protocol excludes persons referred to in Articles 10, 31, 32, 33 and 34 of Regulation (EU) No 536/2014 (including pregnant, birthing or breastfeeding women; adults under legal protection measures such as guardianship or conservatorship; and individuals deprived of liberty). Subject information and informed consent documents (multiple L1 documents including adapted information for sequelae, deceased subjects and follow-up) are provided for participants; only adults (≥18 years) are eligible..
- Pregnancy Exclusion
- 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
- Vulnerable Population
- Vulnerable populations are explicitly considered and partly excluded: the protocol excludes persons referred to in Articles 10, 31, 32, 33 and 34 of Regulation (EU) No 536/2014 (including pregnant, birthing or breastfeeding women; adults under legal protection measures such as guardianship or conservatorship; and individuals deprived of liberty). Subject information and informed consent documents (multiple L1 documents including adapted information for sequelae, deceased subjects and follow-up) are provided for participants; only adults (≥18 years) are eligible.
Inclusion criteria
- {"criterion_text":"- Male or female, aged ≥18 years."}
- {"criterion_text":"- Out-of-hospital cardiac arrest for which resuscitation is decided by the SMUR team."}
- {"criterion_text":"- Medical Out-of-hospital cardiac arrest."}
- {"criterion_text":"- Affiliated with or beneficiary of a social security plan"}
Exclusion criteria
- {"criterion_text":"- Non-medical OHCA (traumatic, drownings, electrocution, asphyxia, overdose, unknown cause)."}
- {"criterion_text":"- 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)."}
- {"criterion_text":"- Individuals referred to in Articles 10, 31, 32, 33 and 34 of Regulation (EU) No 536/2014, including. \tPregnant women, birthing or breastfeeding mothers \tAdults under legal protection measure (such as guardianship, conservatorship) \tIndividuals deprived of liberty due to judicial or administrative decision"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 28-day survival with a favorable neurological function defined as a Modified Rankin Scale (mRS) of score 2 or less at 28-days.","definition_or_measurement_approach":"Defined as a Modified Rankin Scale (mRS) score of 2 or less measured at 28 days."}
Secondary endpoints
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"Assessed during CPR; defined as clinical signs of life including a palpable pulse or measurable blood pressure."}
- {"endpoint_text":"- Survival at hospital admission.","definition_or_measurement_approach":"Alive status at time of hospital admission (binary)."}
- {"endpoint_text":"- 28-day survival.","definition_or_measurement_approach":"Survival status at 28 days after the cardiac arrest (binary)."}
- {"endpoint_text":"- Modified Rankin Scale (mRS) score used as a continuous variable (in contrast with the use of the mRS scale in the primary outcome).","definition_or_measurement_approach":"mRS score evaluated at 28 days and analysed as a continuous variable."}
Recruitment
- Planned Sample Size
- 4336
- Recruitment Window Months
- 48
- Consent Approach
- Participants are adults (≥18 years). Subject information and informed consent forms are provided (multiple L1 documents listed, including adapted information for sequelae, deceased subjects, opposition and follow-up). The protocol lists subject information and ICF documents for use; explicit procedures for emergency/deferred consent are not detailed in the provided CTIS data.
Methods
- Enrollment occurs in the out-of-hospital setting by SMUR (mobile medical team) personnel: eligible patients are identified during out-of-hospital cardiac arrest events for which resuscitation is decided by the SMUR team and randomized on scene.
Geography
- Total Number Of Sites
- 26
- Total Number Of Participants
- 4336
France
- Earliest CTIS Part Ii Submission Date
- 29-09-2025
- Latest Decision Or Authorization Date
- 08-10-2025
- Processing Time Days
- 9
- Number Of Sites
- 26
- Number Of Participants
- 4336
Sites
- Site Name
- Centre Hospitalier De Colmar
- Department Name
- Pôle Urgence Pasteur
- Principal Investigator Name
- Yannick GOTTWALLES
- Principal Investigator Email
- yannick.gottwalles@ch-colmar.fr
- Contact Person Name
- Yannick GOTTWALLES
- Contact Person Email
- yannick.gottwalles@ch-colmar.fr
- Site Name
- Centre Hospitalier Universitaire De Nimes
- Department Name
- Service des urgences, SMUR
- Principal Investigator Name
- Fabien COISY
- Principal Investigator Email
- fabien.cosy@chu-nimes.fr
- Contact Person Name
- Fabien COISY
- Contact Person Email
- fabien.cosy@chu-nimes.fr
- Site Name
- Centre Hospitalier Universitaire De Nice
- Department Name
- Département hospitalo-universitaire de médecine d’urgence DHUMU
- Principal Investigator Name
- Julie CONTENTI
- Principal Investigator Email
- contenti.j@chu-nice.fr
- Contact Person Name
- Julie CONTENTI
- Contact Person Email
- contenti.j@chu-nice.fr
- Site Name
- Centre Hospitalier De La Cote Basque
- Department Name
- Urgences / SAMU/ SMUR
- Principal Investigator Name
- Xavier PEREIRA
- Principal Investigator Email
- x.perreira@ch-cotebasque.fr
- Contact Person Name
- Xavier PEREIRA
- Contact Person Email
- x.perreira@ch-cotebasque.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- SAMU 92 – SMUR Raymond Poincaré, Garches
- Principal Investigator Name
- Armelle SÉVERIN
- Principal Investigator Email
- armelle.severin@aphp.fr
- Contact Person Name
- Armelle SÉVERIN
- Contact Person Email
- armelle.severin@aphp.fr
- Site Name
- Centre Hospitalier Regional Universitaire De Tours
- Department Name
- Département des urgences
- Principal Investigator Name
- Alexandre JEZIORNY
- Principal Investigator Email
- a.jeziorny@chu-tours.fr
- Contact Person Name
- Alexandre JEZIORNY
- Contact Person Email
- a.jeziorny@chu-tours.fr
- Site Name
- Hopital Necker Enfants Malades
- Department Name
- SAMU de Paris – SMUR de NECKER
- Principal Investigator Name
- Alice HUTIN
- Principal Investigator Email
- alice.hutin@aphp.fr
- Contact Person Name
- Alice HUTIN
- Contact Person Email
- alice.hutin@aphp.fr
- Site Name
- Centre Hospitalier Regional Et Universitaire De Brest
- Department Name
- Urgences
- Principal Investigator Name
- Adrien BASSET
- Principal Investigator Email
- adrien.basset@chu-brest.fr
- Contact Person Name
- Adrien BASSET
- Contact Person Email
- adrien.basset@chu-brest.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Urgences
- Principal Investigator Name
- Anthony CHAUVIN
- Principal Investigator Email
- anthony.chauvin@aphp.fr
- Contact Person Name
- Anthony CHAUVIN
- Contact Person Email
- anthony.chauvin@aphp.fr
- Site Name
- Hopital Beaujon
- Department Name
- SMUR
- Principal Investigator Name
- Bénédicte DOUAY
- Principal Investigator Email
- benedicte.douay@aphp.fr
- Contact Person Name
- Bénédicte DOUAY
- Contact Person Email
- benedicte.douay@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Montpellier
- Department Name
- SAMU – SMUR CHU Lapeyronie
- Principal Investigator Name
- Thomas SANCHEZ
- Principal Investigator Email
- thomas-sanchez@chu-montpellier.fr
- Contact Person Name
- Thomas SANCHEZ
- Contact Person Email
- thomas-sanchez@chu-montpellier.fr
- Site Name
- Centre Hospitalier Universitaire De Poitiers
- Department Name
- Service Urgences SAMU SMUR 86
- Principal Investigator Name
- Nicolas MARJANOVIC
- Principal Investigator Email
- nicolas.marjanovic@chu-poitiers.fr
- Contact Person Name
- Nicolas MARJANOVIC
- Contact Person Email
- nicolas.marjanovic@chu-poitiers.fr
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- Urgences-SAMU35-SAS-SMUR-CESU
- Principal Investigator Name
- Nicolas PESCHANSKI
- Principal Investigator Email
- n-peschanski@live.fr
- Contact Person Name
- Nicolas PESCHANSKI
- Contact Person Email
- n-peschanski@live.fr
- Site Name
- Centre Hospitalier Annecy Genevois
- Department Name
- SMUR
- Principal Investigator Name
- Hugo SCHMIT
- Principal Investigator Email
- hschmit@ch-annecygenevois.fr
- Contact Person Name
- Hugo SCHMIT
- Contact Person Email
- hschmit@ch-annecygenevois.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Urgences générales
- Principal Investigator Name
- Clémentine CASSARD
- Principal Investigator Email
- clementine.cassard@aphp.fr
- Contact Person Name
- Clémentine CASSARD
- Contact Person Email
- clementine.cassard@aphp.fr
- Site Name
- Centre Hospitalier Universitaire Rouen
- Department Name
- Département de médecine d'urgence
- Principal Investigator Name
- Marie OZANNE
- Principal Investigator Email
- m.ozanne@chu-rouen.fr
- Contact Person Name
- Marie OZANNE
- Contact Person Email
- m.ozanne@chu-rouen.fr
- Site Name
- Centre hospitalier Annecy Genevois Site Julien en GENEVOIS
- Department Name
- SMUR
- Principal Investigator Name
- Arnaud RELLY
- Principal Investigator Email
- arelly@ch-annecygenevois.fr
- Contact Person Name
- Arnaud RELLY
- Contact Person Email
- arelly@ch-annecygenevois.fr
- Site Name
- CHU Besancon
- Department Name
- Médecine d'urgence et de réanimation
- Principal Investigator Name
- Abdo KHOURY
- Principal Investigator Email
- akhoury@chu-besancon.fr
- Contact Person Name
- Abdo KHOURY
- Contact Person Email
- akhoury@chu-besancon.fr
- Site Name
- Centre Hospitalier Universitaire Reims
- Department Name
- SAU Adultes et SAMU
- Principal Investigator Name
- Stéphane GENNAI
- Principal Investigator Email
- s.gennai@chu-reims.fr
- Contact Person Name
- Stéphane GENNAI
- Contact Person Email
- s.gennai@chu-reims.fr
- Site Name
- Brigade de Sapeurs-Pompiers de Paris
- Department Name
- Division Santé
- Principal Investigator Name
- Simon-Pierre CORCOSTEGUI
- Principal Investigator Email
- simon-pierre.corcostegui@pompiersparis.fr
- Contact Person Name
- Simon-Pierre CORCOSTEGUI
- Contact Person Email
- simon-pierre.corcostegui@pompiersparis.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- CHU PURPAN / SAMU 31-
- Principal Investigator Name
- Bertand GUIHARD
- Principal Investigator Email
- samu.secretariat@chu-toulouse.fr
- Contact Person Name
- Bertand GUIHARD
- Contact Person Email
- samu.secretariat@chu-toulouse.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- SAMU/ SAU
- Principal Investigator Name
- Youri YORDANOV
- Principal Investigator Email
- youri.yordanov@chu-lyon.fr
- Contact Person Name
- Youri YORDANOV
- Contact Person Email
- youri.yordanov@chu-lyon.fr
- Site Name
- Centre Hospitalier Universitaire De Nantes
- Department Name
- Département des urgences SAMU
- Principal Investigator Name
- François JAVAUDIN
- Principal Investigator Email
- francois.javaudin@chu-nantes.fr
- Contact Person Name
- François JAVAUDIN
- Contact Person Email
- francois.javaudin@chu-nantes.fr
- Site Name
- CH SUD Francilien
- Department Name
- SAMU-SMUR 91
- Principal Investigator Name
- Romain BARDELAY
- Principal Investigator Email
- secretariat@samu91.org
- Contact Person Name
- Romain BARDELAY
- Contact Person Email
- secretariat@samu91.org
- Site Name
- Centre Hospitalier Universitaire Grenoble Alpes
- Department Name
- SAMU 38
- Principal Investigator Name
- Nicolas SEGOND
- Principal Investigator Email
- nsegond@chu.grenoble.fr
- Contact Person Name
- Nicolas SEGOND
- Contact Person Email
- nsegond@chu.grenoble.fr
- Site Name
- CHRU De Nancy
- Department Name
- Samu - Smur - Service des Urgences
- Principal Investigator Name
- Tahar CHOUIHED
- Principal Investigator Email
- T.CHOUIHEDMAHJOUB@chru-nancy.fr
- Contact Person Name
- Tahar CHOUIHED
- Contact Person Email
- T.CHOUIHEDMAHJOUB@chru-nancy.fr
Sponsor
Primary sponsor
- Full Name
- CHRU De Nancy
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- France
Investigational products
- Investigational Product Name
- ADRENALINE RENAUDIN 0,50 mg/ml, solution injectable
- Active Substance
- Epinephrine bitartrate
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS BOLUS INJECTION/IV INFUSION
- Route
- Intravenous bolus
- Authorisation Status
- Authorised (marketing authorisation available in FR)
- Starting Dose
- 0.5 mg (IV bolus)
- Dose Levels
- 0.5 mg
- Frequency
- Every 3–5 minutes during cardiopulmonary resuscitation (CPR)
- Investigational Product Name
- ADRENALINE RENAUDIN 1 mg/ml, solution injectable en ampoule
- Active Substance
- Epinephrine bitartrate
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS BOLUS USE
- Route
- Intravenous bolus
- Authorisation Status
- Authorised (marketing authorisation available in FR)
- Starting Dose
- 1 mg (IV bolus)
- Dose Levels
- 1 mg
- Frequency
- Every 3–5 minutes during cardiopulmonary resuscitation (CPR)
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