Mean Arterial Pressure After Out-of-hospital Cardiac Arrest (METAPHORE)

September 4, 2026 updated by: Centre Hospitalier le Mans

Mean Arterial Pressure After Out-of-hospital Cardiac Arrest: the METAPHORE Randomized Trial

Out-of-hospital cardiac arrest is a public health problem for which overall survival is below 10%. Post-cardiac arrest syndrome is the principal cause of death in intensive care units (ICU), due to refractory shock or brain injuries secondary to anoxia. Brain anoxia is responsible for severe neurological sequelae that may be aggravated by cerebral hypoperfusion during the first few hours after the return of spontaneous circulation. Current recommendations are to ensure that arterial blood pressure is sufficient for the perfusion of organs, but no minimum threshold mean arterial pressure (MAP) has been defined. In practice, most teams target a MAP of at least 65 mmHg. Several observational studies have shown a correlation between MAP and neurological prognosis, patients with a higher initial MAP having a better outcome. Recent pilot studies have demonstrated the feasibility of increasing the target MAP after cardiac arrest, but conflicting results have been obtained concerning patient prognosis. These findings may be explained by changes to the autoregulation of the brain after cardiac arrest, with a shift of the curve towards the right, or its abolition. Cerebral blood flow is dependent on MAP, and a target MAP of 65 mmHg for these patients may result in insufficient brain perfusion. Conversely, a too high MAP might cause brain lesions due to vasogenic edema, hemorrhagic complications or excess perfusion in conditions of diminished brain metabolism. An interventional study is required to evaluate the effect of increasing MAP on neurofunctional outcome after cardiac arrest. Given the data available for brain autoregulation, the correlation between MAP and prognosis, and the risks theoretically associated with a higher MAP, investigator plans to compare a standard threshold of MAP (≥ 65 mmHg) with a high threshold of MAP (≥ 90 mmHg). Investigator hypothesizes that a high MAP within the first 24 hours after cardiac arrest will improve neurofunctional outcome.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

1380

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Brest, France, 29609
        • Recruiting
        • CHU Brest - Hôpital de La Cavale Blanche
        • Principal Investigator:
          • Pierre BAILLY, MD
        • Contact:
      • Brive-la-Gaillarde, France, 19100
        • Recruiting
        • CH Brive
        • Principal Investigator:
          • Nicolas PICHON, MD
        • Contact:
      • Caen, France, 14000
        • Recruiting
        • CHU Caen
        • Contact:
        • Principal Investigator:
          • Damien DU CHEYRON, PhD
      • Cannes, France, 06400
        • Not yet recruiting
        • Hopital de Cannes - Simone Veil
        • Contact:
        • Contact:
          • Pierre ALFONSI BERTRAND
        • Principal Investigator:
          • Pierre ALFONSI BERTRAND, MD
      • Cholet, France, 49300
        • Recruiting
        • CH Cholet
        • Contact:
        • Principal Investigator:
          • Fabien JAROUSSEAU, MD
      • Dieppe, France, 76200
        • Recruiting
        • CH Dieppe
        • Contact:
        • Principal Investigator:
          • Antoine MARCHALOT, MD
      • Dijon, France, 21079
        • Recruiting
        • CHU Dijon - Hôpital F. Mitterrand
        • Contact:
        • Principal Investigator:
          • Jean-Pierre QUENOT, PhD
      • La Roche-sur-Yon, France, 85925
        • Recruiting
        • CHD Vendée
        • Contact:
        • Principal Investigator:
          • Gwenhael COLIN, MD
      • Le Chesnay, France, 78150
        • Recruiting
        • CH Versailles
        • Contact:
        • Principal Investigator:
          • Marine PAUL, MD
      • Le Mans, France, 72000
        • Recruiting
        • Centre Hospitalier du Mans
        • Contact:
        • Principal Investigator:
          • Nicolas CHUDEAU, MD
      • Lens, France, 62300
        • Recruiting
        • CH Dr Schaffner
        • Contact:
        • Principal Investigator:
          • Olivier NIGEON, MD
      • Lille, France, 59037
        • Recruiting
        • CHU Lille
        • Contact:
        • Principal Investigator:
          • Patrick GIRARDIE, MD
      • Limoges, France, 87042
        • Recruiting
        • Chu Limoges
        • Contact:
        • Principal Investigator:
          • Marine GOUDELIN, MD
      • Marseille, France, 13005
        • Recruiting
        • APHM - Hôpital de la Timone
        • Principal Investigator:
          • Jérémy BOURENNE, MD
        • Contact:
      • Massy, France, 91300
        • Recruiting
        • Hôpital Jacques Cartier
        • Contact:
        • Principal Investigator:
          • Wulfran BOUGOUIN, PhD
      • Nantes, France, 44093
        • Recruiting
        • CHU Nantes
        • Principal Investigator:
          • Jean-Baptiste Lascarrou, MD
        • Contact:
      • Nice, France, 06001
        • Recruiting
        • CHU Nice - Hôpital Pasteur
        • Contact:
        • Principal Investigator:
          • Denis DOYEN, PhD
      • Nice, France, 06202
        • Recruiting
        • CHU Nice - Hôpital Archet
        • Contact:
        • Principal Investigator:
          • Mathieu JOSWIAK, MD
      • Nîmes, France, 30029
        • Recruiting
        • CHU Nîmes
        • Contact:
        • Principal Investigator:
          • Saber Davide BARBAR, MD
      • Orléans, France, 45067
        • Recruiting
        • CHR Orléans
        • Principal Investigator:
          • Grégoire MULLER, MD
        • Contact:
      • Paris, France, 75014
        • Recruiting
        • Hôpital Cochin
        • Contact:
        • Principal Investigator:
          • Alain CARIOU, PhD
      • Paris, France, 75015
        • Recruiting
        • APHP - Hôpital Européen Georges Pompidou (HEGP)
        • Contact:
        • Principal Investigator:
          • Nicolas BRECHOT, PhD
      • Paris, France, 75651
        • Not yet recruiting
        • Groupe Hospitalier Pitié-Salpêtriere Charles Foix
        • Contact:
        • Principal Investigator:
          • Martin DRES, PhD
      • Poitiers, France, 86021
        • Recruiting
        • CHU Poitiers
        • Contact:
        • Principal Investigator:
          • Arnaud THILLE, PhD
      • Rennes, France, 35000
        • Recruiting
        • CHU Rennes
        • Principal Investigator:
          • Benoit PAINVIN, MD
        • Contact:
      • Saint-Denis, France, 93207
        • Recruiting
        • Centre Cardiologique du Nord
        • Contact:
        • Principal Investigator:
          • Tristan MORICHAU-BEAUCHANT, MD
      • Saint-Nazaire, France, 44600
        • Recruiting
        • Centre hospitalier Saint Nazaire
        • Contact:
        • Principal Investigator:
          • Julien LORBER
      • Strasbourg, France, 67091
        • Recruiting
        • CHRU Strasbourg - Nouvel Hôpital Civil
        • Principal Investigator:
          • Hamid MERDJI, MD
        • Contact:
      • Tours, France, 37044
        • Recruiting
        • CHRU Tours - Hôpital Bretonneau
        • Contact:
        • Principal Investigator:
          • Charlotte SALMON GANDONNIERE, MD
      • Vannes, France, 56000
    • Sarthe
      • Montpellier, Sarthe, France, 34295
        • Not yet recruiting
        • Hopital Lapeyronie
        • Contact:
        • Principal Investigator:
          • Boris Jung, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Admission to ICU following an out-of-hospital cardiac arrest with an initially shockable or non-shockable rhythm ;
  • Sustained ROSC defined as 20 minutes with signs of circulation without the need for chest compressions;
  • Under invasive mechanical ventilation for coma, defined as a Glasgow score ≤ 8/15;
  • Consent from a relative or of a procedure for emergency inclusion.

Exclusion Criteria:

  • Age < 18 years ;
  • In-hospital cardiac arrest (first cardiac arrest);
  • Unwitnessed CA with initial rhythm of asystole
  • Delay between ROSC and attempting randomisation > 6 hours ;
  • Cardiac arrest in a context of multiple trauma ;
  • Cardiac arrest in a context of hemorrhagic shock or severe hemorrhage necessitating hemostasis (surgery or radiological or endoscopic hemostasis) ;
  • Cardiac arrest secondary to an acute brain disease (ischemic or hemorrhagic stroke, subarachnoid hemorrhage, severe traumatic brain injury) ;
  • Refractory shock :

Defined as a MAP < 65 mmHg for more than one hour on norepinephrine or epinephrine at a dose > 1 µg/kg/min despite adequate fluid resuscitation ;

  • Extracorporeal circulatory support prior to inclusion;
  • Known allergy to norepinephrine or to any of its excipients;
  • Decision to limit care before inclusion ;
  • Modified Rankin score of 4 or 5 before cardiac arrest ;
  • Inclusion in another interventional study in which the principal endpoint is neurological prognosis ;
  • Pregnancy or breast feeding ;
  • Adult patient deprived of freedom or under legal protection (patients under guardianship or curatorship) (article L1121-6 of the French Health Code) ;
  • Non-French speaking;
  • Patient already included in this trial ;
  • Absence of social security cover.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: high MAP threshold

Norepinephrine will be titrated to maintain MAP ≥ 90 mmHg. This threshold will be maintained for the 24 hours following inclusion by the perfusion of norepinephrine at an appropriate dose.

From 24 hours after inclusion until ICU discharge, a MAP ≥ 65 mmHg will be targeted
Procedure: Maintain MAP ≥ 90 mmHg
Maintain MAP ≥ 90 mmHg for the 24 hours following inclusion by perfusion of norepinephrine
Active Comparator: standard MAP threshold

Norepinephrine will be titrated to maintain MAP ≥ 65 mmHg. This target MAP will be maintained for 24 hours after randomization through the perfusion of norepinephrine at an appropriate flow rate.

From 24 hours after inclusion until ICU discharge, a MAP ≥ 65 mmHg will be targeted
Procedure: Maintain MAP ≥ 65 mmHg
Maintain MAP ≥ 65 mmHg for 24 hours after randomization through the perfusion of norepinephrine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with a good neurofunctional outcome 180 days after inclusion
Time Frame: 180 days after inclusion
Good neurofunctional outcome will be defined by a modified Rankin scale (mRS) of 0 to 3.This score is a global evaluation scale for disability, with seven levels (0 = no symptoms; 6 = patient dead).This score will be measured by psychologist who will be blinded to the randomization arm.
180 days after inclusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients alive at Intensive Care Unit discharge, at hospital discharge, at day 28 (D28) and six months (D180) after inclusion
Time Frame: From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks), from hospital admission to hospital discharge (up to 12 weeks), 28 days and 180 days after inclusion
Proportion of patients alive at Intensive Care Unit discharge, at hospital discharge, at day 28 (D28) and six months (D180) after inclusion
From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks), from hospital admission to hospital discharge (up to 12 weeks), 28 days and 180 days after inclusion
Proportion of patients alive at Intensive Care Unit discharge with good neurofunctionnal outcome
Time Frame: From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)
Good neurofunctional outcome will be defined by a modified Rankin scale (mRS) of 0 to 3.This score is a global evaluation scale for disability, with seven levels (0 = no symptoms; 6 = patient dead
From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)
Quality of life six months after inclusion
Time Frame: 6 months after inclusion
Quality of life is measured by EuroQol-5D-5L. It's a measure of health-related quality of life and comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). EuroQol-5D-5L could be administered by telephone
6 months after inclusion
Evaluation of Clinical Frailty at six months after inclusion
Time Frame: Six months after inclusion
Clinical Frailty is measured by the Clinical Frailty Scale (CFS). It summarizes the overall level of fitness or frailty of a patient with a score from 1 (very fit) to 9 (terminally ill)
Six months after inclusion
Number of ICU-free days at Day 28
Time Frame: Day 28
Number of ICU-free days is calculated from the number of days alive outside the ICU by Day 28
Day 28
Number of ventilator-free days, number of catecholamine-free days and number of renal replacement therapy-free days at day 28
Time Frame: 28 days after inclusion
Number of ventilator-free days, number of catecholamine-free days and number of renal replacement therapy-free days is calculated from the number of days alive without invasive mechanical ventilation, catecholamine infusion or renal replacement therapy by Day 28
28 days after inclusion
Proportion of patients with acute kidney injury stage 3 and need for renal replacement therapy (RRT) within Intensive Care Unit stay and persistant need for RRT at Intensive Care Unit discharge
Time Frame: From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)
Acute kidney injury stage 3 is defined by at least one of the following criteria: serum creatinine concentration of more than 4 mg/dl (354 µmol/liter) or greater than 3 times the baseline creatinine level, anuria (urine output of 100 ml/day or less) for more than 12 hours, oliguria (urine output below 0.3 ml/kg/h or below 500 ml/day) for more than 24 hours;
From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular complications
Time Frame: within 7 days after inclusion
Cardiovascular complications are assessed by determining the number of patients presenting a severe cardiovascular complication within 7 days of inclusion
within 7 days after inclusion
Neurological complications
Time Frame: within 7 days of inclusion
Neurological complications are asssessed by determining the number of patients presenting stroke (ischemic stroke, subarachnoid hemorrhage or cerebral hematoma), confirmed by imaging (CT-scan or MRI) within 7 days of inclusion (systematic cerebral imaging is not required by the protocol but only in case of clinical suspicion of stroke or for neuroprognostication)
within 7 days of inclusion
Cutaneous complications within 7 days of inclusion
Time Frame: within 7 days of inclusion
Cutaneous complications are assessed by determining the number of patients presenting necrosis of the extremities within 7 days of inclusion
within 7 days of inclusion
Digestive complications within 7 days after inclusion
Time Frame: within 7 days of inclusion
Digestive complications are assessed by determining the number of patients presenting a clinical suspicion of digestive ischemia, confirmed by imaging (CT-scan), endoscopy or exploratory laparotomy, within 7 days of inclusion
within 7 days of inclusion
Major bleeding within 7 days of inclusion
Time Frame: within 7 days of inclusion
Major bleeding is assessed by determining the number of patients presenting one of the International Society on Thrombosis and Haemostasis (ISTH) criteria within 7 days of inclusion (fatal bleeding and/or symptomatic bleeding in a critical area or in an organ such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial or intramuscular with compartment syndrome and/or bleeding causing a fall in hemoglobin level of 20 g.L-1 or more or leading to transfusion of two or more units of red cells)
within 7 days of inclusion
Global complications within 7 days of inclusion
Time Frame: within 7 days of inclusion
Global complications are defined by the proportion of patients with at least one complication (cardiovascular, neurological, cutaneous, digestive or hemorrhagic) within 7 days of inclusion
within 7 days of inclusion
Proportion of patients with a good neurofunctional prognosis at six months in the subgroup of patients with an initial shockable cardiac arrest rhythm and in the subgroup of patients with an initial non-shockable cardiac arrest rhythm
Time Frame: 6 months after inclusion
Proportion of patients with a good neurofunctional prognosis at six months in the subgroup of patients with an initial shockable cardiac arrest rhythm and in the subgroup of patients with an initial non-shockable cardiac arrest rhythm
6 months after inclusion
Proportion of patients with a good neurofunctional prognosis at six months in the subgroup of patients with confirmed chronic arterial hypertension and in the subgroup of patients without chronic arterial hypertension
Time Frame: 6 months after inclusion
Proportion of patients with a good neurofunctional prognosis at six months in the subgroup of patients with confirmed chronic arterial hypertension and in the subgroup of patients without chronic arterial hypertension. Chronic high blood pressure is defined as need for chronic treatment prior to cardiac arrest;
6 months after inclusion
Proportion of patients with good neurofunctional prognosis at six months in the three risks subgroups of patients identified by CAHP score (< 150, 150-200 and > 200).
Time Frame: 6 months after inclusion
Proportion of patients with good neurofunctional prognosis at six months in the three risks subgroups of patients identified by CAHP score (< 150, 150-200 and > 200). The CAHP score represents a simple tool for early stratification of patients admitted in ICU after OHCA, using seven variables (age, rhythm, time from collapse to basic life support, time from basic life support to ROSC, location of cardiac arrest, epinephrine dose and arterial pH)
6 months after inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier le Mans

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 28, 2024

Primary Completion (Estimated)

March 28, 2028

Study Completion (Estimated)

March 28, 2028

Study Registration Dates

First Submitted

August 2, 2022

First Submitted That Met QC Criteria

August 2, 2022

First Posted (Actual)

August 4, 2022

Study Record Updates

Last Update Posted (Actual)

September 9, 2026

Last Update Submitted That Met QC Criteria

September 4, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHM-2022/S03/07

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After publication of the main results, the anonymized data necessary for carrying out additional analyses may be made available upon request addressed to the coordinating investigator and the scientific committee

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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