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    The EU Clinical Trials Register currently displays   42556   clinical trials with a EudraCT protocol, of which   7007   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2020-001620-33
    Sponsor's Protocol Code Number:APHP200033
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-11-09
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2020-001620-33
    A.3Full title of the trial
    HYdrocortisone and VAsopressin in Post-RESuscitation Syndrome
    Hydrocortisone et vasopressine dans l’état de choc post-ressuscitation
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    HYdrocortisone and VAsopressin in Post-RESuscitation Syndrome
    Hydrocortisone et vasopressine dans l’état de choc post-ressuscitation
    A.3.2Name or abbreviated title of the trial where available
    HYVAPRESS
    A.4.1Sponsor's protocol code numberAPHP200033
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorASSISTANCE-PUBLIQUE HOPITAUX DE PARIS (AP-HP)
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMinistery of Health (PHRC-N)
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationASSISTANCE-PUBLIQUE HOPITAUX DE PARIS (AP-HP)
    B.5.2Functional name of contact pointProject Manager
    B.5.3 Address:
    B.5.3.1Street Address1, avenue Claude Vellefaux
    B.5.3.2Town/ cityParis
    B.5.3.3Post code75010
    B.5.3.4CountryFrance
    B.5.4Telephone number33144841749
    B.5.5Fax number33144841701
    B.5.6E-mailahmed.bacha@aphp.fr
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name HYDROCORTISONE UPJOHN 100 mg
    D.2.1.1.2Name of the Marketing Authorisation holderLaboratoires SERB
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Powder for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous bolus use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNHydrocortisone
    D.3.9.3Other descriptive nameHYDROCORTISONE SODIUM SUCCINATE
    D.3.9.4EV Substance CodeSUB02569MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name REVERPLEG® 40 U.I./2 mL
    D.2.1.1.2Name of the Marketing Authorisation holderORPHA-DEVEL HANDELS UND VERTRIEBS GMBH
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNARGIPRESSIN
    D.3.9.1CAS number 113-79-1
    D.3.9.4EV Substance CodeSUB05561MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboPowder for injection
    D.8.4Route of administration of the placeboIntravenous bolus use (Noncurrent)
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Adult cardiac arrest patients with sustained ROSC and hemodynamic failure due to post-resuscitation syndrome
    Patients adultes présentant une récupération d’activité circulatoire spontanée après avoir été réanimés d’un arrêt cardiaque et ayant une insuffisance circulatoire aigue dans le cadre d’un état de choc post-ressuscitation
    E.1.1.1Medical condition in easily understood language
    Post-RESuscitation Syndrome
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to demonstrate the superiority of AVP and hydrocortisone compared with norepinephrine regarding day-30 survival and neurological recovery in post-cardiac arrest patients with hemodynamic failure
    E.2.2Secondary objectives of the trial
    D-30 : all-cause mortality, mortality attributed to irreversible hemodynamic failure, mortality attributed to neurological withdrawal of care, mortality attributed to comorbid withdrawal of care, brain death, mortality attributed to recurrent cardiac arrest, Neurological recovery, Brain damage
    N° of free days between inclusion and D-30 for norepinephrine, AVP, inotropes
    N° of patients successfully weaned from vasopressor support at D-3, -5 and -7
    Atrial fibrillation new onset between inclusion and D-30
    Left ventricular ejection fraction assessed at D-1, 2, 3 and 7
    N° of days between inclusion and D-30 free of mechanical ventilation
    N° of days between inclusion and D-30 free of renal replacement therapy
    Acute kidney injury at D-7 and D-30
    Safety related to AVP use: acute coronary syndrome, mesenteric ischemia, digital ischemia
    Safety related to hydrocortisone use: gastrointestinal bleeding up to D-30, episodes of hyperglycemia up to D 7
    ICU and hospital length of stay
    E.2.3Trial contains a sub-study No
    E.3Principal 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 or emergency procedure
    E.4Principal exclusion criteria
    - Traumatic and 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 mechanical circulatory assistance
    - Gastrointestinal bleeding in the past 6 weeks
    - Pregnant or breastfeeding women
    - Hypersensitivity to arginin-vasopressin and to its excipients
    - Hypersensitivity to hydrocortisone and to its excipients
    - 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
    - Legal protection (i.e. incompetence to provide consent, guardianship, curator or incarceration)
    - No affiliation to a social security system
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint will be a good neurological outcome at day-30. This will be evaluated using the Glasgow Outcome Scale (GOS, addendum 18.5.1) dichotomized as follows: 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.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 30
    E.5.2Secondary end point(s)
    Vital status 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:2019fy}
    Time to neurological withdrawal of care. Withdrawal of care will be based on expectations of a poor neurological recovery based on brain imaging, a neurologic exam, or a formal opinion of a neurologist stating that the prognosis for neurologic recovery is very poor. If an assessment off sedation is not done, there must be other evidence of severe neurologic injury (e.g. severe cerebral edema
    or herniation).
    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 to brain death
    Time to recurrent cardiac arrest
    Proportion of patients dead from a cause not listed above
    Glasgow outcome score – extended at day-30. This score will be evaluated similarly to the primary endpoint
    Neuron-specific enolase (NSE) blood level measured 48 and 72 hours after CA
    Number of days between inclusion and day-30 without
    - catecholamines
    - norepinephrine
    - AVP
    - inotropic support
    Number of patients alive and free of norepinephrine at day-3, -5 and -7
    Number of patients alive and free of AVP at day-3, -5 and -7
    Proportion of patients with new onset of atrial fibrillation at day-30
    Left ventricular ejection fraction at day-1, 2, 3 and 7. Left ventricular ejection fraction will be evaluated using echocardiography (either trans-thoracic or trans-esophageal)
    Number of mechanical ventilation free days at day-30
    Number of renal replacement therapy free days at day-30
    KDIGO classification at day-7 and day-30. The day-30 KDIGO classification will be estimated on the creatinine criteria as the urine criteria will be unlikely available. The estimated glomerular filtration rate will be calculated using the MDRD equation.
    - Proportion of patients with acute coronary syndrome defined according to the international guidelines (2015 ESC guidelines) as to know: the detection of an increase and/or a decrease of cardiac troponin and at least one of the following: (1) symptoms of ischemia, (2) new or presumed new significant ST-T wave changes or left bundle branch block on 12-lead ECG; (3) development of pathological Q waves on ECG, (4) imaging evidence of new or presumed new loss of viable myocardium or regional wall motion abnormality and (5) intracoronary thrombus detected on angiography or autopsy. These findings should be differentiated with the potential initial coronary cause of cardiac arrest.
    - Proportion of patients with mesenteric ischemia at day-30, diagnosed on clinical assessment and a computed tomography angiography or endoscopy
    - Proportion of patients with clinically diagnosed digital ischemia at day-30
    - Proportion of patients with gastro-intestinal bleeding at day-30. Gastrointestinal bleeding will be diagnosed as a clinical gastro-intestinal bleeding simultaneously with a drop of blood hemoglobin level.
    - Proportion of patients with hyperglycemia occurrence, defined as the number of episodes of blood glucose level higher than 11mmol/L between inclusion and day-7
    ICU and hospital lengths of stay (in days)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Day 1
    Day 2
    Day 3
    Day 5
    Day 7
    Day 30
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned17
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months25
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 190
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 190
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patients admitted to the ICU
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    women of child-bearing potential with negative test for pregnancy
    F.4 Planned number of subjects to be included
    F.4.1In the member state380
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-01-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-01-13
    P. End of Trial
    P.End of Trial StatusOngoing
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