Clinical trial NCT05486884: Mean Arterial Pressure After Out-of-hospital Cardiac Arrest
Official title: Mean Arterial Pressure After Out-of-hospital Cardiac Arrest: the METAPHORE Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiac Arrest
Out-of-hospital Cardiac Arrest (OHCA)
Keywords: cardiac arrest
outcome
cerebral blood flow
mean arterial pressure
Lead sponsor: Centre Hospitalier le Mans
Sponsor class: OTHER
First posted: 2022-08-04
Enrollment: 1380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multicenter, randomized, controlled, open study
Primary purpose: TREATMENT

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.


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 ;
* 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.

Primary outcomes:
measure: Proportion of patients with a good neurofunctional outcome 180 days after inclusion
timeFrame: 180 days after inclusion
Secondary outcomes:
measure: Proportion of patients alive at Intensive Care Unit discharge, at hospital discharge, at day 28 (D28) and six months (D180) after inclusion
timeFrame: 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
measure: Proportion of patients alive at Intensive Care Unit discharge with good neurofunctionnal outcome
timeFrame: From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)
measure: Quality of life six months after inclusion
timeFrame: 6 months after inclusion
measure: Evaluation of Clinical Frailty at six months after inclusion
timeFrame: Six months after inclusion
measure: Number of ICU-free days at Day 28
timeFrame: Day 28
measure: Number of ventilator-free days, number of catecholamine-free days and number of renal replacement therapy-free days at day 28
timeFrame: 28 days after inclusion
measure: 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
timeFrame: From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)
Other outcomes:
measure: Cardiovascular complications
timeFrame: within 7 days after inclusion
measure: Neurological complications
timeFrame: within 7 days of inclusion
measure: Cutaneous complications within 7 days of inclusion
timeFrame: within 7 days of inclusion
measure: Digestive complications within 7 days after inclusion
timeFrame: within 7 days of inclusion
measure: Major bleeding within 7 days of inclusion
timeFrame: within 7 days of inclusion
measure: Global complications within 7 days of inclusion
timeFrame: within 7 days of inclusion
measure: 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
timeFrame: 6 months after inclusion
measure: 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
timeFrame: 6 months after inclusion
measure: 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).
timeFrame: 6 months after inclusion
Locations:
city: Brest
country: France
facility: CHU Brest - Hôpital de La Cavale Blanche
city: Brive La Gaillarde
country: France
facility: CH Brive
city: Caen
country: France
facility: CHU Caen
city: Cholet
country: France
facility: CH Cholet
city: Dieppe
country: France
facility: CH Dieppe
city: Dijon
country: France
facility: CHU Dijon - Hôpital F. Mitterrand
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Le Chesnay
country: France
facility: CH Versailles
city: Le Mans
country: France
facility: Centre Hospitalier Du Mans
city: Lens
country: France
facility: CH Dr Schaffner
city: Lille
country: France
facility: CHU Lille
city: Limoges
country: France
facility: CHU Limoges
city: Marseille
country: France
facility: APHM - Hôpital de la Timone
city: Massy
country: France
facility: Hôpital Jacques Cartier
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: CHU Nice - Hôpital Pasteur
city: Nice
country: France
facility: CHU Nice - Hôpital Archet
city: Nîmes
country: France
facility: CHU Nîmes
city: Orléans
country: France
facility: CHR Orléans
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: APHP - Hôpital Européen Georges Pompidou (HEGP)
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU Rennes
city: Saint-Denis
country: France
facility: Centre Cardiologique du Nord
city: Strasbourg
country: France
facility: CHRU Strasbourg - Nouvel Hôpital Civil
city: Tours
country: France
facility: CHRU Tours - Hôpital Bretonneau
city: Vannes
country: France
facility: CH Bretagne Atlantique
Study officials:
References: