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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001620-33 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AVP + placebo hydrocortisone | Experimental | REVERPLEG® 40 IU/2mL+ Placebo of hydrocortisone. |
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| placebo AVP + hydrocortisone | Experimental | Placebo of REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®. |
|
| AVP + hydrocortisone | Experimental | REVERPLEG® 40 IU/2mL + Hydrocortisone 100mg UPJOHN®. |
|
| placebo AVP + placebo hydrocortisone | Experimental | Placebo of REVERPLEG® 40 IU/2mL + placebo of hydrocortisone |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Administration of AVP | Drug | Administration of AVP |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | at day-30 |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause mortality | Vital status at day-30. | 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Guillaume GERI, MD, PhD | Contact | +33 (0) 6 69 24 22 47 | dr.guillaume.geri@gmail.com | |
| Alain Cariou, MD, PhD | Contact | +33 (0)1 58 41 25 01 | alain.cariou@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Guillaume GERI, MD, PhD | Intensive Care Unit, Clinique Ambroise Paré, 92200 Neuilly sur seine | Principal Investigator |
| Alain CARIOU, MD, PhD | Medical Intensive Care Unit, Cochin Hospital, APHP, 75014 Paris | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Intensive care unit, CHU Amiens- Picardie | Recruiting | Amiens | France | |||
| Intensive care unit, CHU Angers |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30710595 | Background | 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. | |
| 40503090 |
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| Administration of placebo AVP | Drug | Administration of placebo AVP |
|
| Administration of placebo hydrocortisone | Drug | Administration of placebo hydrocortisone |
|
| Administration of hydrocortisone | Drug | Administration of hydrocortisone |
|
| 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). | 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). | at day-30 |
| Day-30 brain death | Time to brain death (according to French legislation) | at day-30 |
| mortality attributed to recurrent cardiac arrest | Time to recurrent cardiac arrest | at day-30 |
| Other causes | Proportion of patients dead from a cause not listed above. | 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 | at day-30 |
| Brain damage | Neuron-specific enolase (NSE) blood level measured 48 and 72 hours after CA | at 48 hours and at 72hours |
| Recruiting |
| Angers |
| France |
| Intensive care unit, CHI Robert Ballanger | Recruiting | Aulnay-sous-Bois | France |
| Medical Intensive Care Unit, Ambroise Paré hospital, APHP | Withdrawn | Boulogne-Billancourt | 92100 | France |
| Intensive care unit, CH public du Cotentin | Recruiting | Cherbourg | France |
| Intensive care unit, CHU Dijon | Recruiting | Dijon | France |
| Intensive care unit, Hospices civils de Lyon | Recruiting | Lyon | France |
| Intensive care unit, Hôpital Jacques Cartier | Recruiting | Massy | France |
| Intensive care unit, CHU Montpellier | Recruiting | Montpellier | France |
| Intensive care unit, Brabois hospital | Recruiting | Nancy | France |
| Intensive care unit, Hotel Dieu hospital | Recruiting | Nantes | France |
| Intensive care unit, Clinique Ambroise Paré | Recruiting | Neuilly-sur-Seine | 92200 | France |
| Intensive care unit, Cochin hospital, APHP | Recruiting | Paris | 75014 | France |
| Intensive care unit, André Mignot hospital | Recruiting | Versailles | France |
| 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. |
| ID | Term |
|---|---|
| D003919 | Diabetes Insipidus |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D010900 | Pituitary Diseases |
| D004700 | Endocrine System Diseases |
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