Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44020   clinical trials with a EudraCT protocol, of which   7318   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2020-000620-18
    Sponsor's Protocol Code Number:RC20_0082
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-02-09
    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 number2020-000620-18
    A.3Full title of the trial
    Human recombinant interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a double-blind, international phase 2, randomized, placebo-controlled trial - the PREV-HAP study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Human recombinant interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a double-blind, international phase 2, randomized, placebo-controlled trial - the PREV-HAP study
    A.3.2Name or abbreviated title of the trial where available
    PREV-HAP
    A.4.1Sponsor's protocol code numberRC20_0082
    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 SponsorNantes University Hospital
    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 supportEuropean Commission
    B.4.2CountryEuropean Union
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNantes University Hospital
    B.5.2Functional name of contact pointClinical Research Department
    B.5.3 Address:
    B.5.3.1Street Address5 allée de l'Ile Gloriette
    B.5.3.2Town/ cityNantes
    B.5.3.3Post code44093
    B.5.3.4CountryFrance
    B.5.4Telephone number0033253 48 28 35
    B.5.5Fax number0033253 48 28 36
    B.5.6E-mailbp-prom-regl@chu-nantes.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 Imukin
    D.2.1.1.2Name of the Marketing Authorisation holderClinigen
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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 placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients hospitalized in intensive care units, under mechanical ventilation
    E.1.1.1Medical condition in easily understood language
    Patients hospitalized in intensive care units, under mechanical ventilation
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10022519
    E.1.2Term Intensive care
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10076918
    E.1.2Term Hospital acquired pneumonia
    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 determine whether rHu-IFN-γ as compared with placebo, could reduce the rate of hospital-acquired pneumonia and improve outcomes in patients admitted to intensive care unit and requiring mechanical ventilation.
    E.2.2Secondary objectives of the trial
    • to demonstrate the efficiency of rHuIFN-γ, on pneumonia-associated morbidity and mortality reduction
    • to demonstrate the efficiency of rHuIFN-γ on antimicrobial therapy utilization reduction
    • To describe the safety and tolerability of rHu-IFN-γ
    • To assess the suitability, acceptability, and adaptability of rHu-IFN-γ
    • To assess the economic efficiency of rHuIFN-γ for the prevention of pneumonia
    • To develop biomarkers for the stratification of patients into responders and non-responders of rHuIFN-γ
    • To develop a biobank of blood and respiratory samples collected in humans at risk of hospital-acquired pneumonia
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    At Day 90 an ancillary study will concern 20 patients included in Nantes and their relatives (they could be the legal representative who have signed the consent for the inclusion of their relative, or another relative ; the aim being that it should be the person closest to the patient emotionally, and that it is the same person who answers the questionnaires at M1 and M3), if they consent to.
    Semi-structured interviews will be conducted by a researcher in psychology with patients and relatives (dyads) to gain more insight into the understanding and the interpretation of quantitative data, as recommended by literature on human sciences.
    E.3Principal inclusion criteria
    - Adult patients (18yr to 85yr).
    - Hospitalized in intensive care unit for less than 48 hours.
    - Receiving invasive mechanical ventilation at the time of inclusion.
    - One or more acute organ failure at the time of inclusion among: neurological (Glasgow coma scale <13 before sedation), hemodynamic (norepinephrine, epinephrine, or any other vasopressor at a dose of ≥ 0.1 μg per kilogram of body weight per minute or ≥0.5 mg per hour for at least 6 hours), respiratory (PaO2 / FiO2< 200) and/or renal (creatininemia > 2 fold higher than the basal value and/or oliguria < 0.5 mL/kg/hour for at less 12 hours).
    - Informed consent from a legal representative, or emergency procedure (when possible according to national regulation). If it is not possible to obtain the patient consent prior the inclusion (comatose patients), patient consent for the study continuation will be obtained as soon as deemed possible.
    - Person insured under a health insurance scheme.
    E.4Principal exclusion criteria
    • Pregnant women (serum or urine test), breastfeeding women
    • Patient under legal protection (incl. under guardianship or trusteeship)
    • Hypersensitivity to the active substance (interferon gamma-1b) or known hypersensitivity to related products, such as another interferon, or to any of the following excipients: Mannitol, Disodium succinate hexahydrate, Succinic acid, Polysorbate 20
    • Severe hepatic insufficiency (Child Pugh score B or C)
    • Liver cytolysis with hepatic enzymes (AST and/or ALT) > 5N)
    • Severe chronic renal insufficiency (MDRD Creatinine Clearance < 10 ml/min/1.73m2)
    • Immunodepression (hematologic cancer, aplasia, chemotherapy/radiotherapy for cancer within 3 months prior to the inclusion, known infection Human immunodeficiency virus or concomitant use of any anti-graft rejection drug).
    • Coma after resuscitated cardiac arrest
    • Cervical spinal cord injury
    • Participation to a drug interventional study within 1 month prior to the inclusion
    • Hospital-acquired pneumonia before inclusion in the study during the current hospitalization
    • Sustained hyperlactatemia > 5 mmol/L.
    E.5 End points
    E.5.1Primary end point(s)
    To demonstrate the efficiency of rHuIFN-γ for the prevention of hospital-acquired pneumonia, the primary endpoint is the composite outcome of all-cause mortality at day 28 and/or the occurrence of hospital-acquired pneumonia within 28 days after randomization.
    Hospital acquired-pneumonia is diagnosed after the 48th hour of hospitalization according to European and French guidelines (Torres et al. Eur Respir J 2017; Leone et al. ACCPM 2018) :
    - at least two of the following criteria: body temperature >38°C; leucocytosis>12000 cells per mL, leucopenia <4000 cells per mL, or purulent pulmonary secretions
    - appearance of a new infiltrate or change in an existing infiltrate on chest radiography,
    - positive culture of a respiratory tract samples from mechanically ventilated patients with quantitative culture (for patients with antibiotics < 48h) (thresholds of 104 colony-forming units (CFU) per mL for a bronchoalveolar lavage, 105 CFU/mL for a blind BAL (mini BAL) sample, and ≥105 CFU/mL for a tracheal sample). A semi-quantitative is acceptable, notably for patients with antibiotics >48h. Respiratory samples are obtained before starting any new antibiotic treatment.
    An adjudication committee, composed of 1 investigator by country who will be blinded to the trial-group assignments, will review the medical charts of patients with respiratory tract infections of the 2 other participating countries, in order to review the diagnosis.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 28
    E.5.2Secondary end point(s)
    The secondary outcomes to determine the efficiency of rHu-IFN-γ, on pneumonia-associated morbidity and mortality reduction are:
    -All-cause mortality at D28 and 90.
    -Hospital acquired Pneumonia at D28
    -Bacterial ecology of the 1st episode of HAP (respiratory fluids).
    -Rate of ventilator-associated tracheobronchitis at D28 defined as at least two of the following criteria : body temperature >38°C; leukocytosis>12000 cells per mL, leucopenia <4000 cells per mL, or purulent pulmonary secretions and a positive culture of a respiratory tract samples, without appearance of a new infiltrate or change in an existing infiltrate on chest radiography (Martin-Loeches et al. Lancet Respir Med 2015)
    -Acute Respiratory Distress Syndrome within 28d after randomization
    -Duration of antimicrobial therapy at D28, antibiotic free days at D28 (the number of antibiotic free days is defined as the number of days between D1 and D28 for which living patients don’t receive antibiotics. Dead patients will be ascribed 0 antibiotic free days).
    -Duration of mechanical ventilation at D90, mechanical ventilation free days at D90.
    -Duration of ICU hospitalization at D90, Duration of hospitalization at D90, hospital free days at D90.

    The secondary outcomes to determine the tolerance of rHu-IFN-γ are:
    -Rate of serious adverse effects and suspected unexpected serious adverse reaction (SUSAR) at D15.
    -Rate of leukocytosis, neutropenia, lymphopenia, thrombopenia at D15.
    -Rate of liver cytolysis (Increases in AST and/or ALT) at D15.
    -Rate of pancreatitis (Increase in Lipase) at D15.
    -Fever,headache,nausea at D15.
    -Allergic reaction at D15.
    -Injection site reaction at D15.
    -Myalgia, arthralgia, back pain at D15.

    The secondary outcomes to determine the economic efficiency of rHu-IFN-γ in the prevention of pneumonia are:
    Economic endpoints at M3:Incremental cost effectiveness ratio (ICER). We will assess the economic efficiency of the various interventions compared by performing a cost-effectiveness analysis (CEA) using QALYs (Quality-Adjusted Life-Years) as a measure of effectiveness.

    The secondary outcomes to determine the suitability and acceptability of rHu-IFN-γ from the patients’ and relatives’ perspectives are :

    Suitability
    Changes in health-related quality of life (HRQoL) from one (M1) to three months (M3) after randomization measured with the Short Form (SF)-36 scale validated in French, Greek, and Spanish
    Changes in anxiety and depression from M1 to M3 measured with the HADS scale validated in French, Greek, and Spanish
    Changes in subjective well-being from M1 to M3 measured with the Satisfaction With Life Scale (SWLS) validated in French, Greek, and Spanish
    At M1 and M3, these questionnaires will be filled in by the patient (patient’s perspective) and by one relative (relative’s perspective). The relatives could be the legal representative who have signed the consent for the inclusion of their relative, or another relative ; the aim being that it should be the person closest to the patient emotionally, and that it is the same person who answers the questionnaires at M1 and M3, if they consent to.

    Acceptability
    Adaptation of the patients to their health state and its evolution from M1 to M3 using differential item functioning and response shift analyses for HRQoL, anxiety and depression.
    E.5.2.1Timepoint(s) of evaluation of this end point
    D15, D28 and D90
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy No
    E.6.4Safety No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA18
    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
    Date of collection of all biomarker analyses.
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months27
    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: 150
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    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 Yes
    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
    Treatment of HAP is an emergency, as it is recommended to start the treatment within the 1st hour after diagnosis. The critically ill patients are at risk of pneumonia, and won’t be able to express their consent before the inclusion in the study.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 200
    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)
    No medical care related to the study will be continued after the end of the study.
    The investigator will propose the best medical care to the patient, depending on his or her state of health at the end of the study
    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 Decision2021-02-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-01-19
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA