Postresuscitation SyndromePhase 3HYVAPRESSNCT04591990
HYdrocortisone and VAsopressin in Post-RESuscitation Syndrome
A Phase 3 study testing Administration of AVP and Administration of hydrocortisone in people with Postresuscitation Syndrome, run by Assistance Publique - Hôpitaux de Paris at 14 sites in France.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postresuscitation Syndrome
- What is being tested?
- Administration of AVP and Administration of hydrocortisone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 380 participants
- Where
- 14 sitesFrance
- Study dates
- 27 May 2021to Dec 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
14 sites in 1 country. Contact the study team or a site near you to ask about taking part.
14 sites in 1 country
France14 sites, 13 recruiting
- Recruiting
Intensive care unit, CHU Amiens- Picardie
Amiens
- Recruiting
Intensive care unit, CHU Angers
Angers
- Recruiting
Intensive care unit, CHI Robert Ballanger
Aulnay-sous-Bois
- Withdrawn
Medical Intensive Care Unit, Ambroise Paré hospital, APHP
Boulogne-Billancourt, 92100
- Recruiting
Intensive care unit, CH public du Cotentin
Cherbourg
- Recruiting
Intensive care unit, CHU Dijon
Dijon
- Recruiting
Intensive care unit, Hospices civils de Lyon
Lyon
- Recruiting
Intensive care unit, Hôpital Jacques Cartier
Massy
- Recruiting
Intensive care unit, CHU Montpellier
Montpellier
- Recruiting
Intensive care unit, Brabois hospital
Nancy
- Recruiting
Intensive care unit, Hotel Dieu hospital
Nantes
- Recruiting
Intensive care unit, Clinique Ambroise Paré
Neuilly-sur-Seine, 92200
- Recruiting
Intensive care unit, Cochin hospital, APHP
Paris, 75014
- Recruiting
Intensive care unit, André Mignot hospital
Versailles
About this study
Official title: HYdrocortisone and VAsopressin in Post-REsuscitation Syndrome
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.
- Conditions
- Postresuscitation Syndrome
- Being tested
- Administration of AVP, Administration of placebo AVP, Administration of placebo hydrocortisone, Administration of hydrocortisone
- Keywords
- intensive care, hydrocortisone, vasopressin, post-resuscitation syndrome
- Medical subject headings
- Diabetes Insipidus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration of AVPDrug
Administration of AVP
Administration of placebo AVPDrug
Administration of placebo AVP
Administration of placebo hydrocortisoneDrug
Administration of placebo hydrocortisone
Administration of hydrocortisoneDrug
Administration of hydrocortisone
| Study group | Role | What they receive |
|---|---|---|
| AVP + placebo hydrocortisone | Experimental | REVERPLEG® 40 IU/2mL+ Placebo of hydrocortisone. Receives: Drug: Administration of AVP; Drug: Administration of placebo hydrocortisone |
| placebo AVP + hydrocortisone | Experimental | Placebo of REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®. Receives: Drug: Administration of placebo AVP; Drug: Administration of hydrocortisone |
| AVP + hydrocortisone | Experimental | REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®. Receives: Drug: Administration of AVP; Drug: Administration of hydrocortisone |
| placebo AVP + placebo hydrocortisone | Experimental | Placebo of REVERPLEG® 40 IU/2mL + placebo of hydrocortisone Receives: Drug: Administration of placebo AVP; Drug: Administration of placebo hydrocortisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at day-30
Secondary outcomes (9)
All-cause mortality
Vital status at day-30.
Measured: at day-30
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).
Measured: at day-30
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).
Measured: at day-30
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).
Measured: at day-30
Day-30 brain death
Time to brain death (according to French legislation)
Measured: at day-30
mortality attributed to recurrent cardiac arrest
Time to recurrent cardiac arrest
Measured: at day-30
Other causes
Proportion of patients dead from a cause not listed above.
Measured: at day-30
Neurological recovery at day-30
Glasgow outcome score - extended at day-30. This score will be evaluated similarly to the primary endpoint
Measured: at day-30
Brain damage
Neuron-specific enolase (NSE) blood level measured 48 and 72 hours after CA
Measured: at 48 hours and at 72hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study start27 May 2021
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Postresuscitation SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 380 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guillaume GERI, MD, PhD, Principal investigator, Intensive Care Unit, Clinique Ambroise Paré, 92200 Neuilly sur seineAlain CARIOU, MD, PhD, Study director, Medical Intensive Care Unit, Cochin Hospital, APHP, 75014 Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04591990
- Sponsor's protocol ID
- APHP200033
- Other IDs
- 2020-001620-33
- Acronym
- HYVAPRESS
- Status last verified
- Jun 2025
- First submitted
- 12 Oct 2020
- Last updated
- 12 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 30710595Geri 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.
PubMed 40503090
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HYdrocortisone and VAsopressin in Post-REsuscitation Syndrome
- ClinicalTrials.gov ID
- NCT04591990
- Acronym / sponsor ID
- HYVAPRESS / APHP200033
- Conditions
- Postresuscitation Syndrome
- Keywords
- intensive care, hydrocortisone, vasopressin, post-resuscitation syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 380 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 27 May 2021 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 19 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AVP + placebo hydrocortisone | Experimental | Drug: Administration of AVP, Drug: Administration of placebo hydrocortisoneREVERPLEG® 40 IU/2mL+ Placebo of hydrocortisone. |
| placebo AVP + hydrocortisone | Experimental | Drug: Administration of placebo AVP, Drug: Administration of hydrocortisonePlacebo of REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®. |
| AVP + hydrocortisone | Experimental | Drug: Administration of AVP, Drug: Administration of hydrocortisoneREVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®. |
| placebo AVP + placebo hydrocortisone | Experimental | Drug: Administration of placebo AVP, Drug: Administration of placebo hydrocortisonePlacebo of REVERPLEG® 40 IU/2mL + placebo of hydrocortisone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Administration of AVPAdministration of AVP | Drug | AVP + hydrocortisone, AVP + placebo hydrocortisone |
| Administration of placebo AVPAdministration of placebo AVP | Drug | placebo AVP + hydrocortisone, placebo AVP + placebo hydrocortisone |
| Administration of placebo hydrocortisoneAdministration of placebo hydrocortisone | Drug | AVP + placebo hydrocortisone, placebo AVP + placebo hydrocortisone |
| Administration of hydrocortisoneAdministration of hydrocortisone | Drug | AVP + hydrocortisone, placebo AVP + hydrocortisone |
Primary outcome
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.
9 secondary outcomes
All-cause mortality
Time frame: at day-30
Mortality attributed to irreversible hemodynamic failure
Time frame: at day-30
Mortality attributed to neurological withdrawal of care
Time frame: at day-30
Mortality attributed to comorbid withdrawal of care
Time frame: at day-30
Day-30 brain death
Time frame: at day-30
mortality attributed to recurrent cardiac arrest
Time frame: at day-30
Other causes
Time frame: at day-30
Neurological recovery at day-30
Time frame: at day-30
Brain damage
Time frame: at 48 hours and at 72hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2025.
- Background: PubMed 30710595Witten 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.
- Derived from this study: PubMed 40503090Geri 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.
- Individual participant dataSharing planned: No
Related trials for Postresuscitation Syndrome
RecruitingObservational study
Repository for Sepsis and Postresuscitation Samples
Cardiac Arrest, Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
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
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Administration of AVP and Administration of hydrocortisone in people with Postresuscitation Syndrome, run by Assistance Publique - Hôpitaux de Paris at 14 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Guillaume GERI, MD, PhD (+33 (0) 6 69 24 22 47, dr.guillaume.geri@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurological outcome (time frame: at day-30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04591990, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2025.