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Mean Arterial Pressure After Out-of-hospital Cardiac Arrest

Not Applicable
Recruiting
Conditions
Cardiac Arrest
Out-of-hospital Cardiac Arrest (OHCA)
Interventions
Procedure: Maintain MAP ≥ 65 mmHg
Procedure: Maintain MAP ≥ 90 mmHg
Registration Number
NCT05486884
Lead Sponsor
Centre Hospitalier le Mans
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1380
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
standard MAP thresholdMaintain MAP ≥ 65 mmHgNorepinephrine 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
high MAP thresholdMaintain MAP ≥ 90 mmHgNorepinephrine 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
Primary Outcome Measures
NameTimeMethod
Proportion of patients with a good neurofunctional outcome 180 days after inclusion180 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.

Secondary Outcome Measures
NameTimeMethod
Proportion of patients alive at Intensive Care Unit discharge, at hospital discharge, at day 28 (D28) and six months (D180) after inclusionFrom 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

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 with good neurofunctionnal outcomeFrom Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)

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

Quality of life six months after inclusion6 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

Evaluation of Clinical Frailty at six months after inclusionSix 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)

Number of ICU-free days at Day 28Day 28

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

Number of ventilator-free days, number of catecholamine-free days and number of renal replacement therapy-free days at day 2828 days after inclusion

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

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 dischargeFrom Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)

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;

Trial Locations

Locations (27)

CHU Brest - Hôpital de La Cavale Blanche

🇫🇷

Brest, France

CH Brive

🇫🇷

Brive La Gaillarde, France

CHU Caen

🇫🇷

Caen, France

CH Cholet

🇫🇷

Cholet, France

CH Dieppe

🇫🇷

Dieppe, France

CHU Dijon - Hôpital F. Mitterrand

🇫🇷

Dijon, France

CHD Vendée

🇫🇷

La Roche-sur-Yon, France

CH Versailles

🇫🇷

Le Chesnay, France

Centre Hospitalier Du Mans

🇫🇷

Le Mans, France

CH Dr Schaffner

🇫🇷

Lens, France

CHU Lille

🇫🇷

Lille, France

CHU Limoges

🇫🇷

Limoges, France

APHM - Hôpital de la Timone

🇫🇷

Marseille, France

Hôpital Jacques Cartier

🇫🇷

Massy, France

CHU Nantes

🇫🇷

Nantes, France

CHU Nice - Hôpital Pasteur

🇫🇷

Nice, France

CHU Nice - Hôpital Archet

🇫🇷

Nice, France

CHU Nîmes

🇫🇷

Nîmes, France

CHR Orléans

🇫🇷

Orléans, France

Hôpital Cochin

🇫🇷

Paris, France

APHP - Hôpital Européen Georges Pompidou (HEGP)

🇫🇷

Paris, France

CHU Poitiers

🇫🇷

Poitiers, France

CHU Rennes

🇫🇷

Rennes, France

Centre Cardiologique du Nord

🇫🇷

Saint-Denis, France

CHRU Strasbourg - Nouvel Hôpital Civil

🇫🇷

Strasbourg, France

CHRU Tours - Hôpital Bretonneau

🇫🇷

Tours, France

CH Bretagne Atlantique

🇫🇷

Vannes, France

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