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RecruitingNCT04591990HYVAPRESSUpdated Jun 12, 2025

HYdrocortisone and VAsopressin in Post-RESuscitation Syndrome

A Phase 3 interventional study of Administration of AVP and Administration of placebo AVP in Postresuscitation Syndrome, sponsored by Assistance Publique - Hôpitaux de Paris. Recruiting at 14 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-06-12.

Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
380
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Postresuscitation Syndrome

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Keywords

  • intensive care
  • hydrocortisone
  • vasopressin
  • post-resuscitation syndrome
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Factorial assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
380 participants (estimated)

Study arms

  • Experimental
    AVP + placebo hydrocortisone

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

    Drug: Administration of AVP · Drug: Administration of placebo hydrocortisone

  • Experimental
    placebo AVP + hydrocortisone

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

    Drug: Administration of placebo AVP · Drug: Administration of hydrocortisone

  • Experimental
    AVP + hydrocortisone

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

    Drug: Administration of AVP · Drug: Administration of hydrocortisone

  • Experimental
    placebo AVP + placebo hydrocortisone

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

    Drug: Administration of placebo AVP · Drug: Administration of placebo hydrocortisone

Interventions

  • DrugAdministration of AVP

    Administration of AVP

  • DrugAdministration of placebo AVP

    Administration of placebo AVP

  • DrugAdministration of placebo hydrocortisone

    Administration of placebo hydrocortisone

  • DrugAdministration of hydrocortisone

    Administration of hydrocortisone

05

What researchers measure

Primary outcomes

  1. Neurological outcome

    The primary endpoint will be the good neurological outcome at day-30. This will be evaluated using the Glasgow Outcome Scale (GOS, addendum 18.5.1) dichotomized as follow: good neurological outcome for categories 4 and 5 and poor neurological outcome or death for categories 3, 2 and 1. The GOS will be obtained at day-30 from an in-hospital visit if the patient is still hospitalized or from telephone contact with patients, relatives or general practitioners.

    Time frame: at day-30

Secondary outcomes

  1. All-cause mortality

    Vital status at day-30.

    Time frame: at day-30

  2. Mortality attributed to irreversible hemodynamic failure

    Time to irreversible cardiovascular failure defined as death in pharmacologically uncontrollable hypotension (mean arterial blood pressure \< 60 mmHg) despite maximal ICU care, or withdrawal of care based on same, as previously defined (Witten L, Resuscitation 2019).

    Time frame: at day-30

  3. Mortality attributed to neurological withdrawal of care

    Time to neurological withdrawal of care. Withdrawal of care will be based on expectations of a poor neurological recovery based on most recent guidelines (Sandroni C, ICM 2015).

    Time frame: at day-30

  4. Mortality attributed to comorbid withdrawal of care

    Time to comorbid withdrawal of care. Comorbid withdrawal of care or refusal of life-sustaining therapy based on the expectation of a poor quality of life. This may be related to a preexisting or newly discovered terminal illness or other serious medical condition (e.g. dementia or cancer).

    Time frame: at day-30

  5. Day-30 brain death

    Time to brain death (according to French legislation)

    Time frame: at day-30

  6. mortality attributed to recurrent cardiac arrest

    Time to recurrent cardiac arrest

    Time frame: at day-30

  7. Other causes

    Proportion of patients dead from a cause not listed above.

    Time frame: at day-30

  8. Neurological recovery at day-30

    Glasgow outcome score - extended at day-30. This score will be evaluated similarly to the primary endpoint

    Time frame: at day-30

  9. Brain damage

    Neuron-specific enolase (NSE) blood level measured 48 and 72 hours after CA

    Time frame: at 48 hours and at 72hours

06

Study locations

13 of 14 sites recruiting
  • Intensive care unit, CHU Amiens- Picardie
    Amiens, France
    Recruiting
  • Intensive care unit, CHU Angers
    Angers, France
    Recruiting
  • Intensive care unit, CHI Robert Ballanger
    Aulnay-sous-Bois, France
    Recruiting
  • Medical Intensive Care Unit, Ambroise Paré hospital, APHP
    Boulogne-Billancourt, 92100, France
    Withdrawn
  • Intensive care unit, CH public du Cotentin
    Cherbourg, France
    Recruiting
  • Intensive care unit, CHU Dijon
    Dijon, France
    Recruiting
  • Intensive care unit, Hospices civils de Lyon
    Lyon, France
    Recruiting
  • Intensive care unit, Hôpital Jacques Cartier
    Massy, France
    Recruiting
  • Intensive care unit, CHU Montpellier
    Montpellier, France
    Recruiting
  • Intensive care unit, Brabois hospital
    Nancy, France
    Recruiting
  • Intensive care unit, Hotel Dieu hospital
    Nantes, France
    Recruiting
  • Intensive care unit, Clinique Ambroise Paré
    Neuilly-sur-Seine, 92200, France
    Recruiting
  • Intensive care unit, Cochin hospital, APHP
    Paris, 75014, France
    Recruiting
  • Intensive care unit, André Mignot hospital
    Versailles, France
    Recruiting
07

References and documents

Publications

  • 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. PubMed 30710595 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT04591990
Lead sponsor
Assistance Publique - Hôpitaux de Paris
Responsible party
Sponsor
First posted
Oct 19, 2020
Start date
May 27, 2021
Primary completion
Dec 2025 (estimated)
Completion
Dec 2025 (estimated)
Last update
Jun 12, 2025

Study contacts

Guillaume GERI, MD, PhD
Contact
dr.guillaume.geri@gmail.com
+33 (0) 6 69 24 22 47
Alain Cariou, MD, PhD
Contact
alain.cariou@aphp.fr
+33 (0)1 58 41 25 01
Guillaume GERI, MD, PhD
principal investigator · Intensive Care Unit, Clinique Ambroise Paré, 92200 Neuilly sur seine
Alain CARIOU, MD, PhD
study director · Medical Intensive Care Unit, Cochin Hospital, APHP, 75014 Paris

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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