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

Primary Purpose

Cardiac Arrest

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Maintain MAP ≥ 90 mmHg
Maintain MAP ≥ 65 mmHg
Sponsored by
Centre Hospitalier le Mans
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Arrest focused on measuring cardiac arrest, outcome, cerebral blood flow, mean arterial pressure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Centre Hospitalier Du Mans

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

high MAP threshold

standard MAP threshold

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).Ihis score will be measured by psychologist who will be blinded to the randomization arm.

Secondary Outcome Measures

Full Information

First Posted
August 2, 2022
Last Updated
August 2, 2022
Sponsor
Centre Hospitalier le Mans
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1. Study Identification

Unique Protocol Identification Number
NCT05486884
Brief Title
Mean Arterial Pressure After Out-of-hospital Cardiac Arrest
Acronym
METAPHORE
Official Title
Mean Arterial Pressure After Out-of-hospital Cardiac Arrest: the METAPHORE Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2023 (Anticipated)
Primary Completion Date
January 1, 2027 (Anticipated)
Study Completion Date
April 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier le Mans

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Arrest
Keywords
cardiac arrest, outcome, cerebral blood flow, mean arterial pressure

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Prospective, multicenter, randomized, controlled, open study
Masking
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
Allocation
Randomized
Enrollment
1608 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
high MAP threshold
Arm Type
Experimental
Arm Description
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
Arm Title
standard MAP threshold
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Procedure
Intervention Name(s)
Maintain MAP ≥ 90 mmHg
Intervention Description
Maintain MAP ≥ 90 mmHg for the 24 hours following inclusion by perfusion of norepinephrine
Intervention Type
Procedure
Intervention Name(s)
Maintain MAP ≥ 65 mmHg
Intervention Description
Maintain MAP ≥ 65 mmHg for 24 hours after randomization through the perfusion of norepinephrine
Primary Outcome Measure Information:
Title
Proportion of patients with a good neurofunctional outcome 180 days after inclusion
Description
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.
Time Frame
180 days after inclusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christelle JADEAU
Phone
+33244710781
Email
cjadeau@ch-lemans.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Nicolas CHUDEAU
Phone
+33243432458
Email
nchudeau@ch-lemans.fr
Facility Information:
Facility Name
Centre Hospitalier Du Mans
City
Le Mans
ZIP/Postal Code
72000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christelle JADEAU
Phone
+33244710781
Email
cjadeau@ch-lemans.fr
First Name & Middle Initial & Last Name & Degree
Nicolas CHUDEAU, MD

12. IPD Sharing Statement

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Mean Arterial Pressure After Out-of-hospital Cardiac Arrest

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