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

Sponsor

Centre Hospitalier le Mans (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05486884

Collaborator

(none)

1,608

Enrollment

Location

Arms

Anticipated Duration (Months)

35.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Arrest	Procedure: Maintain MAP ≥ 90 mmHg Procedure: Maintain MAP ≥ 65 mmHg	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1608 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, multicenter, randomized, controlled, open studyProspective, multicenter, randomized, controlled, open study

Masking:

Single (Outcomes Assessor)

Masking Description:

Score mRS will be measured by a psychologist during a telephone interview 180 days after inclusion. The psychologist will be blinded to the randomization arm

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2027

Anticipated Study Completion Date :

Apr 1, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Proportion of patients with a good neurofunctional outcome 180 days after inclusion [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).Ihis score will be measured by psychologist who will be blinded to the randomization arm.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 ;
No-flow duration > 10 minutes or unknown (time between CA and the start of cardiopulmonary resuscitation) ;
Low-flow duration > 45 minutes (time between the start of cardiopulmonary resuscitation and ROSC) ;
Unwitnessed CA with initial rhythm of asystole
Time between ROSC and inclusion > 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 circulatory insufficiency:

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 for refractory cardiogenic shock before inclusion ;
Extracorporeal respiratory support by Extra-Corporeal Membrane Oxygenation (ECMO) for severe acute respiratory distress syndrome before inclusion ;
Extracoporeal circulatory support before ROSC
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 under legal protection (incapable adult or ward of court) ;
Patient already included in this trial ;
Absence of social security cover.