Impact of Low Dose Epinephrine in the Management of Out-of-hospital Cardiac Arrest on Neurological Outcome (Low-EPI)

Impact of Low Dose Epinephrine in the Management of Out-of-hospital Cardiac Arrest on Neurological Outcome: A Multicenter Randomized and Double-blind Trial.

This study will test whether a lower dose of epinephrine (0.5 mg) given during emergency treatment for out-of-hospital cardiac arrest helps more patients survive with good brain function, compared to the standard dose (1 mg). Adults who experience cardiac arrest outside the hospital and are treated by emergency medical teams will be randomly assigned to receive either the low dose or the standard dose of epinephrine. The study will compare survival and neurological outcomes between the two groups over 28 days.

Study Overview

• Status: Not yet recruiting
• Conditions: Out-of-hospital Cardiac Arrest (OHCA)
• Intervention / Treatment: Drug: Epinephrine 0.5 mg intravenous bolus; Drug: Epinephrine 1 mg intravenous bolus

• Study Type: Interventional
• Enrollment (Estimated): 4336
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tahar CHOUIHED, MD, PhD; Phone Number: 0033383157322; Email: T.CHOUIHEDMAHJOUB@chru-nancy.fr
• Study Contact Backup: Name: Nicolas Girerd, MD PhD; Phone Number: 0033383157322; Email: n.girerd@chru-nancy.fr

Study Locations

• France
  • Annecy, France
    • CH Annecy
    • Contact: Hugo SCHMIT, MD PHD; Phone Number: +33 4 50 63 63 63; Email: hschmit@ch-annecygenevois.fr
    • Principal Investigator: Hugo SCHMIT, MD PhD
  • Bayonne, France
    • Centre Hospitalier de la Cote Basque
    • Contact: Pereira Xavier, MD; Phone Number: +33 5 59 44 35 35; Email: xpereira@ch-cotebasque.fr
    • Principal Investigator: Xavier Pereira, MD
  • Besançon, France
    • CHU Besançon
    • Contact: Abdo KHOURY, MD; Phone Number: 0033381668836; Email: akhoury@chu-besancon.fr
    • Principal Investigator: Abdo KHOURY, MD
  • Brest, France
    • CHU Brest
    • Contact: Adrien Basset, MD; Phone Number: +33 2 98 22 33 33; Email: adrien.basset@chu-brest.fr
    • Principal Investigator: Adrien Basset, MD
  • Colmar, France
    • Chu Colmar
    • Principal Investigator: Yannick GOTTWALLES, MD
    • Contact: Yannick GOTTWALLES, MD; Phone Number: +33 3 89 12 40 00; Email: yannick.GOTTWALLES@ch-colmar.fr
  • Corbeil-Essonnes, France
    • Ch Sud Francilien
    • Principal Investigator: Romain BARDELAY, MD
    • Contact: Romain BARDELAY, MD; Phone Number: 0033161696169; Email: secretariat@samu91.org
  • Courbevoie, France
    • Brigade de Sapeurs-Pompiers de Paris
    • Contact: Simon-Pierre CORCOSTEGUI, MD; Phone Number: 0033149047425; Email: simon-pierre.corcostegui@pompiersparis.fr
    • Principal Investigator: Simon-Pierre CORCOSTEGUI, MD
  • La Tronche, France
    • Centre Hospitalier Universitaire Grenoble Alpes
    • Principal Investigator: Nicolas Segond, MD
    • Contact: Nicolas SEGOND, MD; Phone Number: 0033476767575; Email: nsegond@chu.grenoble.fr
  • Lyon, France
    • Hospices Civils de Lyon
  • Montpellier, France
    • CHU Montpellier
    • Contact: Thomas SANCHEZ, MD; Phone Number: +33 4 67 33 67 33; Email: thomas-sanchez@chu-montpellier.fr
    • Principal Investigator: Thomas Sanchez, MD
  • Nancy, France
    • CHRU Nancy
    • Principal Investigator: Tahar CHOUIHED, MD, PhD
    • Contact: Tahar CHOUIHED, MD, PhD; Phone Number: 0033383858585; Email: T.CHOUIHEDMAHJOUB@chru-nancy.fr
  • Nantes, France
    • Centre Hospitalier Universitaire de Nantes
    • Contact: François JAVAUDIN, MD; Email: francois.javaudin@chu-nantes.fr
    • Principal Investigator: François JAVAUDIN, MD
  • Nice, France
    • CHU Nice
    • Contact: Julie CONTENTI, MD PHD; Phone Number: +33 4 92 03 77 77; Email: contenti.j@chu-nice.fr
    • Principal Investigator: Julie Contenti, MD PhD
  • Nîmes, France
    • CHU Nimes
    • Principal Investigator: Fabien COISY, MD
    • Contact: Fabien COISY, MD; Phone Number: +33 4 66 68 68 68; Email: fabien.coisy@chu-nimes.fr
  • Paris, France
    • Hôpital Lariboisière
    • Contact: Anthony CHAUVIN, MD PHD; Phone Number: +33 1 49 95 65 65; Email: anthony.chauvin@aphp.fr
    • Contact: clementine.cassard@aphp.fr
    • Principal Investigator: Anthony Chauvin, MD PhD
  • Paris, France
    • Hôpital Beaujon
    • Contact: Bénédicte DOUAY, MD; Phone Number: +33 1 40 87 50 00; Email: benedicte.douay@aphp.fr
    • Principal Investigator: Benedicte Douay, MD
  • Paris, France
    • AP-HP Hôpital Necker
    • Contact: Alice HUTIN, MD; Phone Number: +33 1 44 49 40 00; Email: alice.hutin@aphp.fr
    • Principal Investigator: Alice HUTIN, MD
  • Paris, France
    • La Pitie Salpetriere
    • Contact: clementine.cassard@aphp.fr
    • Contact: Clémentine Cassard, MD; Phone Number: +33 1 42 16 00 00
    • Principal Investigator: Célmentine Cassard, MD
  • Paris, France
    • Raymond Poincaré Hospital
    • Contact: Armelle Severin, MD; Phone Number: +33 1 47 10 79 00; Email: armelle.severin@aphp.fr
    • Principal Investigator: Armelle Severin, MD
  • Poitiers, France
    • CHU Poitiers
    • Contact: Nicolas MARJANOVIC, MD; Phone Number: +33 5 49 44 44 44; Email: nicolas.MARJANOVIC@chu-poitiers.fr
    • Principal Investigator: Nicolas MARJANOVIC, MD PhD
  • Reims, France
    • Centre Hospitalier Universitaire Reims
    • Contact: Stéphane GENNAI, MD; Phone Number: 0033326787878; Email: s.gennai@chu-reims.fr
    • Principal Investigator: Stéphane GENNAI, MD
  • Rennes, France
    • CHU Rennes
    • Contact: Nicolas PESCHANSKI, MD PHD; Phone Number: +33 2 99 28 43 21; Email: nicolas.PESCHANSKI@chru-rennes.fr
    • Principal Investigator: Nicolas PESCHANSKI, MD PhD
  • Rouen, France
    • CHU Rouen
    • Contact: Marie OZANNE, MD; Phone Number: +33 2 32 88 89 90; Email: m.ozanne@chu-rouen.fr
    • Principal Investigator: Marie Ozanne, MD
  • Saint-Julien-en-Genevois, France
    • Centre hospitalier Annecy Genevois Site Julien en GENEVOIS
    • Contact: Arnaud RELLY, MD; Phone Number: 003345063601; Email: arelly@ch-annecygenevois.fr
    • Principal Investigator: Arnaud RELLY, MD
  • Toulouse, France
    • Centre Hospitalier Universitaire de Toulouse
    • Principal Investigator: Bertrand GUIHARD, MD
    • Contact: Bertand GUIHARD, MD; Phone Number: 0033561772233; Email: samu.secretariat@chu-toulouse.fr
  • Tours, France
    • CHU Tours
    • Contact: Alexandre JEZIORNY, MD; Phone Number: +33 2 47 47 47 47; Email: a.JEZIORNY@chu-tours.fr
    • Principal Investigator: Alexandre JEZIORNY, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Male or female, aged ≥18 years. Out-of-hospital cardiac arrest for which resuscitation is decided by the SMUR team.

Medical Out-of-hospital cardiac arrest. Affiliated with or beneficiary of a social security plan

Exclusion Criteria:

• Non-medical Out-of-hospital cardiac arrest (traumatic, drownings, electrocution, asphyxia, overdose, unknown cause).

• Out-of-hospital cardiac arrest without advanced life support (Do Not Attempt Resuscitation order, body finding, the decision not to attempt advanced life support is at the physician's discretion).

  • 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epinephrine 0.5 mg intravenous bolus every 3-5 minutes during Cardio-Pulmonary Resuscitation	Drug: Epinephrine 0.5 mg intravenous bolus; Epinephrine 0.5 mg/mL solution for injection, administered as a 0.5 mg intravenous bolus every 3 to 5 minutes during cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest. T
Active Comparator: Epinephrine 1 mg IV bolus every 3-5 minutes during Cardio-Pulmonary Resuscitation; Epinephrine 1 mg intravenous bolus every 3-5 minutes during Cardio-Pulmonary Resuscitation	Drug: Epinephrine 1 mg intravenous bolus; Epinephrine 1 mg/mL solution for injection, administered as a 1 mg intravenous bolus every 3 to 5 minutes during cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) score	The mRS score is a validated score measuring neurologic outcomes after cardio-pulmonary resuscitation (CPR) : mRS 0. No symptoms.; mRS 1. No significant disability. Able to perform all usual activities, despite some symptoms.; mRS 2. Slight disability. Independent but unable to perform usual activities (work, sports, leisure). mRS 3. Moderate disability. Requires assistance, but able to walk alone.; mRS 4. Moderately severe disability. Walking assistance and daily living activities not possible. mRS 5. Major disability. Bedridden, incontinent and requires constant nursing care and attention.; mRS 6. Death.	28-day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return of Spontaneous Circulation (ROSC).	Return of Spontaneous Circulation (ROSC) during cardiopulmonary resuscitation, defined as clinical signs of life including palpable pulse or blood pressure.	Periprocedural period of cardiopulmonary resuscitation
Vital status	Survival at hospital admission.	Periprocedural period of cardiopulmonary resuscitation
vital status	28-day survival	28 days post-cardiac arrest
Modified Rankin Scale (mRS) score.	Modified Rankin Scale (mRS) score used as a continuous variable (in contrast with the use of the mRS scale in the primary outcome). The mRS score is a validated score measuring neurologic outcomes after cardio-pulmonary resuscitation (CPR) : mRS 0. No symptoms.; mRS 1. No significant disability. Able to perform all usual activities, despite some symptoms.; mRS 2. Slight disability. Independent but unable to perform usual activities (work, sports, leisure). mRS 3. Moderate disability. Requires assistance, but able to walk alone.; mRS 4. Moderately severe disability. Walking assistance and/or daily living activities not possible. mRS 5. Major disability. Bedridden, incontinent and requires constant nursing care and attention.; mRS 6. Death. The mRS score will be assessed 28 days after cardiac arrest.	28 days post-cardiac arrest

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Emergency Medicine; Cardiac Arrest; Neurological Outcome; Epinephrine,
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Catechols; Phenols; Benzene Derivatives; Alcohols; Amino Alcohols; Ethanolamines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Epinephrine
• Other Study ID Numbers: 2021PI170; 2023-505349-26-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No