DRUG
Administration of AVP
Administration of AVP
HYdrocortisone and VAsopressin in Post-RESuscitation Syndrome
Status
Recruiting
Phase
Phase 3
Enrollment
380
Locations
14
Results
Not posted
Publications
2
Study summary
What the protocol is testing.
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.
Full 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.
Interventions
Treatment arms and agents.
DRUG
Administration of placebo AVP
Administration of placebo AVP
DRUG
Administration of placebo hydrocortisone
Administration of placebo hydrocortisone
DRUG
Administration of hydrocortisone
Administration of hydrocortisone
Timeline
From registration to results.
First posted
Oct 19, 2020
Study start
May 27, 2021
Primary completion
Dec 2025
Study completion
Dec 2025
Results posted
Not reported
Registry updated
Jun 12, 2025
Outcomes
What the study measures.
Primary outcomes
Neurological outcome
Time frame · at day-30
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.
Secondary outcomes
All-cause mortality
Time frame · at day-30
Vital status at day-30.
Mortality attributed to irreversible hemodynamic failure
Time frame · at day-30
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).
Mortality attributed to neurological withdrawal of care
Time frame · at day-30
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).
Mortality attributed to comorbid withdrawal of care
Time frame · at day-30
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).
Day-30 brain death
Time frame · at day-30
Time to brain death (according to French legislation)
mortality attributed to recurrent cardiac arrest
Time frame · at day-30
Time to recurrent cardiac arrest
Other causes
Time frame · at day-30
Proportion of patients dead from a cause not listed above.
Neurological recovery at day-30
Time frame · at day-30
Glasgow outcome score - extended at day-30. This score will be evaluated similarly to the primary endpoint
Brain damage
Time frame · at 48 hours and at 72hours
Neuron-specific enolase (NSE) blood level measured 48 and 72 hours after CA
Eligibility
Who can take part.
- Minimum age
- 18 Years
- Maximum age
- Not reported
- Sex
- ALL
- 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: * 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.
Study locations
14 registered sites.
France. Showing up to 24 locations stored in the fast local snapshot.
Intensive care unit, CHU Amiens- Picardie
Amiens, France
Intensive care unit, CHU Angers
Angers, France
Intensive care unit, CHI Robert Ballanger
Aulnay-sous-Bois, France
Medical Intensive Care Unit, Ambroise Paré hospital, APHP
Boulogne-Billancourt, France
Intensive care unit, CH public du Cotentin
Cherbourg, France
Intensive care unit, CHU Dijon
Dijon, France
Intensive care unit, Hospices civils de Lyon
Lyon, France
Intensive care unit, Hôpital Jacques Cartier
Massy, France
Intensive care unit, CHU Montpellier
Montpellier, France
Intensive care unit, Brabois hospital
Nancy, France
Intensive care unit, Hotel Dieu hospital
Nantes, France
Intensive care unit, Clinique Ambroise Paré
Neuilly-sur-Seine, France
Intensive care unit, Cochin hospital, APHP
Paris, France
Intensive care unit, André Mignot hospital
Versailles, France
Publications
Results and literature.
PMID 30710595 ↗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.PMID 40503090 ↗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.
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