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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:2020-000296-21
    Sponsor's Protocol Code Number:APHP191110
    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:2020-03-11
    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 number2020-000296-21
    A.3Full title of the trial
    Rapid rEcognition of COrticosteroid Resistant or sentive Sepsis RECORDS
    A Multicentre Concealedā€Allocation Multi-arms Blinded Randomized Controlled Trial to Identify the Best Sepsis Population for Corticotherapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Patients Admitted to ICU with proven or suspected infection as the main diagnosis
    A.3.2Name or abbreviated title of the trial where available
    RECORDS
    A.4.1Sponsor's protocol code numberAPHP191110
    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 supportRHU 2019
    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
    B.5.2Functional name of contact pointMyriem Carrier /Akim Souag
    B.5.3 Address:
    B.5.3.1Street AddressDRCI_Hôpital Saint-Louis, 1 avenue Claude Vellefaux
    B.5.3.2Town/ cityparis
    B.5.3.3Post code75010
    B.5.3.4CountryFrance
    B.5.4Telephone number330 1 44 84 17 52/15
    B.5.5Fax number3301 44 84 17 01
    B.5.6E-mailmyriem.carrier@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.2.1.1.2Name of the Marketing Authorisation holderSERB
    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.3.1Product nameHémisuccinate d'hydrocortisone
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    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.2.1.1.2Name of the Marketing Authorisation holderASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
    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.3.1Product nameFludrocortisone
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPNasogastric use (Noncurrent)
    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.8.4Route of administration of the placeboIntravenous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboNasogastric use (Noncurrent)
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients admitted to the ICU proven or suspected infection as the main diagnosis.

    E.1.1.1Medical condition in easily understood language
    Patients with Sepsis
    E.1.1.2Therapeutic area Diseases [C] - Bacterial Infections and Mycoses [C01]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10040050
    E.1.2Term Sepsis NOS
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the effect hydrocortisone plus fludrocortisone vs. placebo on a composite of death or persistent organ dysfunction – defined as continued dependency on mechanical ventilation, new renal replacement therapy, or vasopressors – assessed at 90 days on intensive care unit (ICU) adults and having different biological profiles for immune responses and corticosteroids bioactivity .
    E.2.2Secondary objectives of the trial
    To compare the effect of hydrocortisone plus fludrocortisone vs. placebo on:
    1) 6-month mortality;
    2) 6-month HRQoL;
    3) organ function (days 1, 2, 3, 4, 7, 10, 14, and 28 if in ICU);
    4) hyperglyceamia as defined by glucose levels of >8.3 mmol/L (150mg/dL) (daily up to day 28)
    5) hypernatremia as defined by serum sodium levels of >150mmol/L (daily up to day 28)
    6) secondary infection (daily up to day 90)
    7) beeding in the gastrointestinal tract defined by clinical evidence of active bleeding and need for blood transfusion OR hemostatic endoscopic or surgical procedures
    8) neurological cognitive dysfunction defined as by low score on the PROMIS Adult cognitive function score.
    9) neuromuscular weakness defined as a grade of 2 or more on Muscular Disability Rating Scale (MDRS).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Patients ≥ 18 years old,
    2) Admitted to the ICU with proven or suspected infection as the main diagnosis,
    3) Community acquired pneumonia related sepsis OR vasopressors dependency (norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine) OR septic shock (Singer 2016: vasopressor to maintain mean blood pressure of at least 65 mmHg and lactate levels above 2 mmol/l) OR acute respiratory distress syndrome (ARDS – Ranieri 2012: a- acute onset, i.e. within one week of an apparent clinical insult and with progression of respiratory syndrome, b- bilateral opacities on chest imaging not explained by other pulmonary pathologies, e.g. pleural effusion, atelectasis, nodules etc, c- no evidence for heart failure or volume overload, d- PaO2/FiO2 ≤ 300 mm Hg, - PEEP ≥ 5 cm H2O
    4) Patient who has signed an informed and written consent whevener he/she is able of consent, if not ascent from his/her representant whenever he/she is present at time of screening for inclusion
    5) Patients who have been tested for RECORDS specific biomarkers
    o CIRCI negative
    o Endocan < 2 ng/L
    o GILZ < x (threshold currently under study)
    o CPD positive
    o Transcriptomic SRS2
    o Endotype B
    6) Affiliation to a social security system or to an universal health coverage (Couverture Maladie Universelle, CMU);
    7) Patients under guardianship or curatorship will be included;
    8) Patients in case of simple emergency (legal definition) will be included.
    E.4Principal exclusion criteria
    1) Pregnancy
    2) Expected death or withdrawal of life-sustaining treatments within 48 hours
    3) Previously enrolled in this study or in an other ineterventional study,
    4) Hypersensitivity to hydrocortisone or fludrocortisone or any of their excipients ( SPC),
    5) Women of childbearing potential not using contraception,
    6) Nursing women.
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome will be 90-Day organ dysfunction, ventilation and vasopressors free survival after randomization, which is a composite of day 90 mortality and survival free days off vasopressors and mechanical ventilation, and with SOFA score ≤6. Such composite outcomes are increasingly used in ICU trials as reliable patient-centered outcomes .

    Data on the vital status at day 90 after randomisation will be collected from the medical files (including electronic medical files for the entire hospital) and phone calls to patients and their designated contact persons. The primary endpoint is a binary variable. Patients will be classed as positive outcome if they are alive at day 90 and free of vasopressor therapy, mechanical ventilation and organ dysfunction. Patients will be classed as negative outcome if they either died in the first 90 days after randomisation or if they remained vasopressor or mechanical ventilation dependent or with a SOFA score >6 beyond 28-days.
    E.5.1.1Timepoint(s) of evaluation of this end point
    90 days
    E.5.2Secondary end point(s)
    The secondary outcomes will include:
    1) Mortality at 7, 14, 28 day and 6 months.
    2) Vasopressor free days: defined as the number of days with permanent hemodynamic stability in the absence of any vasopressor agent, norepinephrine, phenylephrine, epinephrine, dopamine, vasopressine or its analogs, and soever. When a patient will die on vasopressor therapy, the corresponding vasopressor free day will be 0.
    3) Mechanical ventilation free days: defined as the number of days with permanent appropriate oxygenation while the patients is extubated and breathing spontaneously, i.e. no need for non invasive ventilation, high flow oxygen or CPAP. Other uses of non-invasive ventilation (e.g., chronic night-time use for chronic obstructive pulmonary disease) are not counted. When a patient will die on mechanical ventilation or will be discharge home on mechanical ventilation, the corresponding mechanical ventilation free day will be 0.
    4) Organ dysfunction free days: Organ function (including renal function) will be assessed by the SOFA score (Vincent 1996). Organ dysfunction will be defined by a SOFA score of > 6 (Annane 2018). Organ dysfunction free days are defined by the number of days with os total SOFA score of 6 or less. When a patient will die on vasopressor therapy, the corresponding vasopressor free day will be 0.
    5) HRQoL in 6-month survivors assessed by the EuroQol-5D (EQ-5D). This questionnaire is a standardised measure of health status developed to provide a simple, generic measure of health for clinical and economic appraisal. It is made up for two components; health state description and evaluation. The health status is measured in terms of five dimensions; mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In evaluation part, the respondents evaluate their overall health status using the visual analogue scale. See Figure 4.
    6) Proportion of patients with a decision to withhold and/or withdraw active treatments
    7) ICU and hospital length of stay
    8) Rate of re-admission to the ICU during the 180 days after randomization
    9) Safety endpoints:
    - Proportion of patients affected by any serious adverse events associated with corticosteroids, among the following: hospital-acquired infections, hyperglycemia, hypernatremia, neurological disorders (coma, stroke or muscle weakness, as defined below) during the 90 days after randomization
    - Coma will be defined as a Glasgow coma score < 8
    - Neurologic sequelae will be assessed according to the score on the Muscular Disability Rating Scale (MDRS), with a score of 1 indicating no deficit, 2 minor deficit with no functional disability, 3 distal motor deficit, 4 mild-to-moderate proximal motor deficit, and 5 severe proximal motor deficit.
    - Proportion of patients affected by hospital-acquired infections (CTINILS. Définition des infections associées aux soins. 2007)
    - Number of episodes of hyperglycemia (blood glucose levels >150mg/dl) during ICU stay (or up to day 90, whichever occurs first)
    - Number of episodes of hypernatremia (serum sodium > 145 mmol/L) during ICU stay (or up to day 90, whichever occurs first)
    - Glasgow coma scale at ICU and hospital discharge .
    - Number of patients with an episode of stroke (medical diagnosis as registered in the medical file) during ICU stay (or up to day 90, whichever occurs first)
    - Gastroduodenal bleeding requiring transfusion or hemostatic treatment during ICU stay (or up to day 90, whichever occurs first).
    E.5.2.1Timepoint(s) of evaluation of this end point
    180 days
    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 Yes
    E.6.13.1Other scope of the trial description
    The RECORDS Trial is a multicentre concealed-allocation multi-arms, parallel-group, adaptive blinded RCT. Patients will be randomly assigned to hydrocortisone plus fludrcortisone or placebos for 7 days. Our recruitment target is 1800 patients with full follow-up. Since loss to follow up is rare in critical care trials with outcomes measured at day 90, we do not expect missing data for the primary outcome.
    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 trial2
    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 concerned19
    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 No
    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 years4
    E.8.9.1In the Member State concerned months6
    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: 900
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 900
    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 Yes
    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 No
    F.4 Planned number of subjects to be included
    F.4.1In the member state1800
    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 Decision2020-04-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-04-03
    P. End of Trial
    P.End of Trial StatusOngoing
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