Mean Arterial Pressure After Out-of-hospital Cardiac Arrest

Cardiac Arrest Clinical Trial

— METAPHORE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05486884
• Other study ID #: CHM-2022/S03/07
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2023
• Est. completion date: April 1, 2027

Study information

• Verified date: July 2022
• Source: Centre Hospitalier le Mans
• Contact: Christelle JADEAU
• Phone: +33244710781
• Email: cjadeau[@]ch-lemans.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1608
• Est. completion date: April 1, 2027
• Est. primary completion date: January 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest
• Out-of-Hospital Cardiac Arrest

Intervention

Procedure:
• Maintain MAP = 90 mmHg
Maintain MAP = 90 mmHg for the 24 hours following inclusion by perfusion of norepinephrine
• Maintain MAP = 65 mmHg
Maintain MAP = 65 mmHg for 24 hours after randomization through the perfusion of norepinephrine

Locations

Country	Name	City	State
France	Centre Hospitalier Du Mans	Le Mans

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier le Mans

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	180 days after inclusion