CClinicalTrials.gg
RecruitingNCT05486884METAPHOREUpdated Sep 9, 2026

Mean Arterial Pressure After Out-of-hospital Cardiac Arrest

An interventional study of Maintain MAP ≥ 90 mmHg and Maintain MAP ≥ 65 mmHg in Cardiac Arrest and Out-of-hospital Cardiac Arrest (OHCA), sponsored by Centre Hospitalier le Mans. Recruiting at 31 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-09.

Sponsored by Centre Hospitalier le Mans · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
1,380
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Cardiac Arrest
  • Out-of-hospital Cardiac Arrest (OHCA)

Keywords

  • cardiac arrest
  • outcome
  • cerebral blood flow
  • mean arterial pressure
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
1,380 participants (estimated)

Study arms

  • 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

  • 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

Interventions

  • ProcedureMaintain MAP ≥ 90 mmHg

    Maintain MAP ≥ 90 mmHg for the 24 hours following inclusion by perfusion of norepinephrine

  • ProcedureMaintain MAP ≥ 65 mmHg

    Maintain MAP ≥ 65 mmHg for 24 hours after randomization through the perfusion of norepinephrine

05

What researchers measure

Primary outcomes

  1. Proportion of patients with a good neurofunctional outcome 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.

    Time frame: 180 days after inclusion

Secondary outcomes

  1. Proportion of patients alive at Intensive Care Unit discharge, at hospital discharge, at day 28 (D28) and six months (D180) after inclusion

    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

  2. Proportion of patients alive at Intensive Care Unit discharge with good neurofunctionnal outcome

    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

    Time frame: From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)

  3. Quality of life six 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

    Time frame: 6 months after inclusion

  4. Evaluation of Clinical Frailty at 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)

    Time frame: Six months after inclusion

  5. Number of ICU-free days at Day 28

    Number of ICU-free days is calculated from the number of days alive outside the ICU by Day 28

    Time frame: Day 28

  6. Number of ventilator-free days, number of catecholamine-free days and number of renal replacement therapy-free days at day 28

    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

    Time frame: 28 days after inclusion

  7. 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

    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;

    Time frame: From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)

Other outcomes

  1. Cardiovascular complications

    Cardiovascular complications are assessed by determining the number of patients presenting a severe cardiovascular complication within 7 days of inclusion

    Time frame: within 7 days after inclusion

  2. Neurological complications

    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)

    Time frame: within 7 days of inclusion

  3. Cutaneous complications 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

    Time frame: within 7 days of inclusion

  4. Digestive complications within 7 days after 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

    Time frame: within 7 days of inclusion

  5. Major bleeding 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)

    Time frame: within 7 days of inclusion

  6. Global complications 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

    Time frame: within 7 days of inclusion

  7. 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

    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

  8. 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

    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;

    Time frame: 6 months after inclusion

  9. 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).

    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)

    Time frame: 6 months after inclusion

06

Study locations

28 of 31 sites recruiting
  • Hopital Lapeyronie
    Montpellier, Sarthe 34295, France
    Not yet recruiting
  • CHU Brest - Hôpital de La Cavale Blanche
    Brest, 29609, France
    Recruiting
  • CH Brive
    Brive-la-Gaillarde, 19100, France
    Recruiting
  • CHU Caen
    Caen, 14000, France
    • Damien DU CHEYRON, PhD · Contact · ducheyron-d@chu-caen.fr · +332 31 06 47 16
    • Damien DU CHEYRON, PhD · Principal investigator
    Recruiting
  • Hopital de Cannes - Simone Veil
    Cannes, 06400, France
    • Pierre ALFONSI BERTRAND, MD · Contact · p.alfonsibertrand@ch-cannes.fr · +33492186708
    • Pierre ALFONSI BERTRAND · Contact
    • Pierre ALFONSI BERTRAND, MD · Principal investigator
    Not yet recruiting
  • CH Cholet
    Cholet, 49300, France
    Recruiting
  • CH Dieppe
    Dieppe, 76200, France
    • Antoine MARCHALOT, MD · Contact · amarchalot@ch-dieppe.fr · +332 32 14 72 53
    • Antoine MARCHALOT, MD · Principal investigator
    Recruiting
  • CHU Dijon - Hôpital F. Mitterrand
    Dijon, 21079, France
    Recruiting
  • CHD Vendée
    La Roche-sur-Yon, 85925, France
    • Gwenhael COLIN, MD · Contact · gwenhael.colin@ght85.fr · +332 51 44 60 35
    • Gwenhael COLIN, MD · Principal investigator
    Recruiting
  • CH Versailles
    Le Chesnay, 78150, France
    • Marine PAUL, MD · Contact · mpaul@ch-versailles.fr · +331 39 63 83 59
    • Marine PAUL, MD · Principal investigator
    Recruiting
  • Centre Hospitalier Du Mans
    Le Mans, 72000, France
    • Christelle JADEAU · Contact · cjadeau@ch-lemans.fr · +33244710781
    • Nicolas CHUDEAU, MD · Principal investigator
    Recruiting
  • CH Dr Schaffner
    Lens, 62300, France
    • Olivier NIGEON, MD · Contact · onigeon@ch-lens.fr · +332 21 69 10 88
    • Olivier NIGEON, MD · Principal investigator
    Recruiting
  • CHU Lille
    Lille, 59037, France
    Recruiting
  • CHU Limoges
    Limoges, 87042, France
    Recruiting
  • APHM - Hôpital de la Timone
    Marseille, 13005, France
    • Jérémy BOURENNE, MD · Contact · Jeremy.BOURENNE@ap-hm.fr · +334 13 42 95 66
    • Jérémy BOURENNE, MD · Principal investigator
    Recruiting
  • Hôpital Jacques Cartier
    Massy, 91300, France
    Recruiting
  • CHU Nantes
    Nantes, 44093, France
    Recruiting
  • CHU Nice - Hôpital Pasteur
    Nice, 06001, France
    • Denis DOYEN, PhD · Contact · doyen.d@chu-nice.fr · +334 92 03 55 10
    • Denis DOYEN, PhD · Principal investigator
    Recruiting
  • CHU Nice - Hôpital Archet
    Nice, 06202, France
    • Mathieu JOSWIAK, MD · Contact · joswiak.m@chu-nice.fr · +334 92 03 55 10
    • Mathieu JOSWIAK, MD · Principal investigator
    Recruiting
  • CHU Nîmes
    Nîmes, 30029, France
    • Saber Davide BARBAR, MD · Contact · saber.barbar@chu-nimes.fr · +334 66 68 33 20
    • Saber Davide BARBAR, MD · Principal investigator
    Recruiting
  • CHR Orléans
    Orléans, 45067, France
    Recruiting
  • Hôpital Cochin
    Paris, 75014, France
    • Alain CARIOU, PhD · Contact · alain.cariou@aphp.fr · +331 58 41 25 17
    • Alain CARIOU, PhD · Principal investigator
    Recruiting
  • APHP - Hôpital Européen Georges Pompidou (HEGP)
    Paris, 75015, France
    • Nicolas BRECHOT, PhD · Contact · nicolas.brechot@aphp.fr · +331 56 09 23 42
    • Nicolas BRECHOT, PhD · Principal investigator
    Recruiting
  • Groupe Hospitalier Pitié-Salpêtriere Charles Foix
    Paris, 75651, France
    • Martin DRES, PhD · Contact · martin.dres@aphp.fr · +33142167797
    • Martin DRES, PhD · Principal investigator
    Not yet recruiting
  • CHU Poitiers
    Poitiers, 86021, France
    Recruiting
  • CHU Rennes
    Rennes, 35000, France
    Recruiting
  • Centre Cardiologique du Nord
    Saint-Denis, 93207, France
    • Tristan MORICHAU-BEAUCHANT, MD · Contact · t.morichau-beauchant@ccn.fr · +331 49 33 48 91
    • Tristan MORICHAU-BEAUCHANT, MD · Principal investigator
    Recruiting
  • Centre hospitalier Saint Nazaire
    Saint-Nazaire, 44600, France
    Recruiting
  • CHRU Strasbourg - Nouvel Hôpital Civil
    Strasbourg, 67091, France
    Recruiting
  • CHRU Tours - Hôpital Bretonneau
    Tours, 37044, France
    • Charlotte SALMON GANDONNIERE, MD · Contact · charlotte.salmon@univ-tours.fr · +332 47 47 38 55
    • Charlotte SALMON GANDONNIERE, MD · Principal investigator
    Recruiting
  • CH Bretagne Atlantique
    Vannes, 56000, France
    Recruiting
07

References and documents

Publications

  • Chudeau N, Saulnier P, Parot-Schinkel E, Lascarrou JB, Colin G, Barbar SD, Painvin B, Pichon N, Du Cheyron D, Marchalot A, Jarousseau F, Delbove A, Morichau-Beauchant T, Girardie P, Salmon Gandonniere C, Thille AW, Quenot JP, Bailly P, Goudelin M, Martino F, Nigeon O, Merdji H, Brechot N, Bourenne J, Bougouin W, Muller G, Jozwiak M, Doyen D, Rouanet E, Cariou A, Guitton C; AfterROSC Network; CRICS TRIGGERSep F-CRIN Network. Mean arterial pressure after out-of-hospital cardiac arrest (METAPHORE): study protocol for a multicentre controlled trial with blinded primary outcome assessor. BMJ Open. 2025 Apr 25;15(4):e096997. doi: 10.1136/bmjopen-2024-096997. PubMed 40280607 ↗

Individual participant data

Plan to share: Yes — 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

08

Registry details

Key details

Study ID
NCT05486884
Lead sponsor
Centre Hospitalier le Mans
Responsible party
Sponsor
First posted
Aug 4, 2022
Start date
Sep 28, 2024
Primary completion
Mar 28, 2028 (estimated)
Completion
Mar 28, 2028 (estimated)
Last update
Sep 9, 2026

Study contacts

Christelle JADEAU
Contact
cjadeau@ch-lemans.fr
+33244710781
Nicolas CHUDEAU
Contact
nchudeau@ch-lemans.fr
+33243432458

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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