HYdrocortisone and VAsopressin in Post-RESuscitation Syndrome

NCT ID: NCT04591990

Last Updated: 2025-06-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

380 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-27

Study Completion Date

2025-12-31

Brief Summary

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The primary objective is to demonstrate the superiority of arginine-vasopressin (AVP) and hydrocortisone compared with norepinephrine regarding day-30 survival and neurological recovery in post-cardiac arrest patients with hemodynamic failure.

Detailed Description

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For patients successfully resuscitated who got restoration of spontaneous circulation (ROSC) after cardiopulmonary resuscitation (CPR), the course is usually marked by a post-resuscitation syndrome including multiple organ failures of various intensity and anoxic brain damage. The cardiocirculatory failure usually dominates the clinical picture, and it often leads to multiorgan failure. This hemodynamic failure is multifactorial, including at various levels vasoplegia, myocardial dysfunction, endotoxin release and adrenal dysfunction and is at least partly related to a hormonal defect that could be counteracted by hormonal supplementation. Such a substitutive opotherapy by hydrocortisone and AVP could improve hemodynamic failure and decrease overall mortality in this setting.

This trial is a superiority multicentric trial and patients will be randomized in a 1:1:1:1 ratio using an electronic CRF.

Investigational medicinal products:

\- Arginin-vasopressin or AVP (REVERPLEG) The solution for infusion is prepared by diluting 40 I.U. REVERPLEG® with sodium chloride 9 mg/ml (0.9%) solution. The total volume after dilution should be 50 ml (equivalent to 0.8 I.U. AVP per ml).

AVP will be administered according to mean arterial pressure to target a 65mmHg blood pressure for max 3 days.

\- HYDROCORTISONE HEMISUCCINATE Vials with lyophilisate (100mg hydrocortisone) are provided by SERB laboratory. Hydrocortisone hemisuccinate will be administered as a 50mg intravenous bolus every 6 hours after an initial dose of 100mg, for 7 consecutive days. Stop of treatment by hydrocortisone will be performed without tapering.

Comparator treatment: placebos.

17 ICU centers in France will participate to this study targetting 380 patient's enrollment in the study.

Conditions

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Postresuscitation Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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AVP + placebo hydrocortisone

REVERPLEG® 40 IU/2mL+ Placebo of hydrocortisone.

Group Type EXPERIMENTAL

Administration of AVP

Intervention Type DRUG

Administration of AVP

Administration of placebo hydrocortisone

Intervention Type DRUG

Administration of placebo hydrocortisone

placebo AVP + hydrocortisone

Placebo of REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®.

Group Type EXPERIMENTAL

Administration of placebo AVP

Intervention Type DRUG

Administration of placebo AVP

Administration of hydrocortisone

Intervention Type DRUG

Administration of hydrocortisone

AVP + hydrocortisone

REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®.

Group Type EXPERIMENTAL

Administration of AVP

Intervention Type DRUG

Administration of AVP

Administration of hydrocortisone

Intervention Type DRUG

Administration of hydrocortisone

placebo AVP + placebo hydrocortisone

Placebo of REVERPLEG® 40 IU/2mL + placebo of hydrocortisone

Group Type EXPERIMENTAL

Administration of placebo AVP

Intervention Type DRUG

Administration of placebo AVP

Administration of placebo hydrocortisone

Intervention Type DRUG

Administration of placebo hydrocortisone

Interventions

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Administration of AVP

Administration of AVP

Intervention Type DRUG

Administration of placebo AVP

Administration of placebo AVP

Intervention Type DRUG

Administration of placebo hydrocortisone

Administration of placebo hydrocortisone

Intervention Type DRUG

Administration of hydrocortisone

Administration of hydrocortisone

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Adult patients (\>18y)
* Cardiac arrest (in-hospital or out-of-hospital) with sustained ROSC (\> 30 minutes) admitted to the ICU
* Post-resuscitation shock defined as arterial hypotension (SAP \< 90 mmHg or MAP \< 65 mmHg) unresponsive to adequate fluid loading, which occurred within the first 24 hours after ROSC and requiring norepinephrine/epinephrine continuous infusion at a dose greater or equal to 0.2µg/kg/min for at least 3 hours
* A maximal delay between the start of norepinephrine infusion and randomization of 9 hours
* Informed written consent of the patient or a legally authorized close relative.

Exclusion Criteria

* Evidence for a traumatic or a neurological cause of cardiac arrest
* Shock due to uncontrolled haemorrhage
* Previously known adrenal insufficiency
* Limitation of life-sustaining therapies
* Ongoing treatment by any steroids, whatever the dose
* Ongoing extra-corporeal circulatory assistance
* Gastrointestinal bleeding in the past 6 weeks
* Pregnant or breastfeeding women
* Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants, if applicable
* Hypersensitivity to arginin-vasopressin and to its excipients
* Hypersensitivity to hydrocortisone and to its excipients
* Legal protection (i.e. incompetence to provide consent, guardianship, curator or incarceration)
* No affiliation with the French health care system.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Guillaume GERI, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Intensive Care Unit, Clinique Ambroise Paré, 92200 Neuilly sur seine

Alain CARIOU, MD, PhD

Role: STUDY_DIRECTOR

Medical Intensive Care Unit, Cochin Hospital, APHP, 75014 Paris

Locations

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Intensive care unit, CHU Amiens- Picardie

Amiens, , France

Site Status RECRUITING

Intensive care unit, CHU Angers

Angers, , France

Site Status RECRUITING

Intensive care unit, CHI Robert Ballanger

Aulnay-sous-Bois, , France

Site Status RECRUITING

Medical Intensive Care Unit, Ambroise Paré hospital, APHP

Boulogne-Billancourt, , France

Site Status WITHDRAWN

Intensive care unit, CH public du Cotentin

Cherbourg, , France

Site Status RECRUITING

Intensive care unit, CHU Dijon

Dijon, , France

Site Status RECRUITING

Intensive care unit, Hospices civils de Lyon

Lyon, , France

Site Status RECRUITING

Intensive care unit, Hôpital Jacques Cartier

Massy, , France

Site Status RECRUITING

Intensive care unit, CHU Montpellier

Montpellier, , France

Site Status RECRUITING

Intensive care unit, Brabois hospital

Nancy, , France

Site Status RECRUITING

Intensive care unit, Hotel Dieu hospital

Nantes, , France

Site Status RECRUITING

Intensive care unit, Clinique Ambroise Paré

Neuilly-sur-Seine, , France

Site Status RECRUITING

Intensive care unit, Cochin hospital, APHP

Paris, , France

Site Status RECRUITING

Intensive care unit, André Mignot hospital

Versailles, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Guillaume GERI, MD, PhD

Role: CONTACT

+33 (0) 6 69 24 22 47

Alain Cariou, MD, PhD

Role: CONTACT

+33 (0)1 58 41 25 01

References

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Witten L, Gardner R, Holmberg MJ, Wiberg S, Moskowitz A, Mehta S, Grossestreuer AV, Yankama T, Donnino MW, Berg KM. Reasons for death in patients successfully resuscitated from out-of-hospital and in-hospital cardiac arrest. Resuscitation. 2019 Mar;136:93-99. doi: 10.1016/j.resuscitation.2019.01.031. Epub 2019 Jan 30.

Reference Type BACKGROUND
PMID: 30710595 (View on PubMed)

Geri G, Lascarrou JB, Levy B, Asfar P, Muller G, Legriel S, Ricome S, Cour M, Klouche K, Sauneuf B, Quenot JP, Bougouin W, Cariou A; HYVAPRESS investigators. Hydrocortisone and arginine vasopressin in post-resuscitation shock: the HYVAPRESS trial. Resusc Plus. 2025 May 19;24:100982. doi: 10.1016/j.resplu.2025.100982. eCollection 2025 Jul.

Reference Type DERIVED
PMID: 40503090 (View on PubMed)

Other Identifiers

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2020-001620-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP200033

Identifier Type: -

Identifier Source: org_study_id

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