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    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   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).

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    Summary
    EudraCT Number:2018-000059-42
    Sponsor's Protocol Code Number:31/17/0334
    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:2018-04-09
    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 number2018-000059-42
    A.3Full title of the trial
    Comparison of short infusion versus prolonged infusion of ceftolozane-tazobactam among patients with ventilator associated-pneumonia to Pseudomonas aeruginosa in intensive care units
    Comparaison de l’administration en perfusion courte versus perfusion prolongée du ceftolozane - tazobactam chez des patients de réanimation présentant une pneumopathie acquise sous ventilation mécanique à Pseudomonas aeruginosa
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Comparison of short infusion versus prolonged infusion of ceftolozane-tazobactam among patients with ventilator associated-pneumonia to Pseudomonas aeruginosa in intensive care units
    Comparaison de l’administration en perfusion courte versus perfusion prolongée du ceftolozane - tazobactam chez des patients de réanimation présentant une pneumopathie acquise sous ventilation mécanique à Pseudomonas aeruginosa

    A.3.2Name or abbreviated title of the trial where available
    CEFTOREA
    CEFTOREA
    A.4.1Sponsor's protocol code number31/17/0334
    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 SponsorCHU DE TOULOUSE
    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 supportCHU DE TOULOUSE
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCHU DE TOULOUSE
    B.5.2Functional name of contact pointBELLOC AUDREY
    B.5.3 Address:
    B.5.3.1Street AddressDRDI HOTEL DIEU 2 RUE VIGUERIE
    B.5.3.2Town/ cityTOULOUSE
    B.5.3.3Post code31059
    B.5.3.4CountryFrance
    B.5.4Telephone number+330561777032
    B.5.5Fax number+3305 61 77 84 11
    B.5.6E-mailbelloc.a@chu-toulouse.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 ZERBAXA
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme Ltd
    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 Concentrate for solution for infusion
    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 Yes
    D.3.11.13.1Other medicinal product typeANTIBIOTIC
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Ventilator associated-pneumonia to Pseudomonas aeruginosa in intensive care units
    Pneumopathie acquise sous ventilation mécanique à Pseudomonas aeruginosa en service de réanimation
    E.1.1.1Medical condition in easily understood language
    Nosocomial pneumopathy
    Pneumopathie nosocomiale
    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 20.1
    E.1.2Level LLT
    E.1.2Classification code 10052596
    E.1.2Term Nosocomial 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
    The main objective of this study is to compare the median exposures at pharmacokinetic equilibrium of the two modalities of administration: 4-hours infusion of ceftolozane-tazobactam at a dosage of 2 g three times a day (tid) vs 1-hour infusion of 2 g tid.
    L’objectif principal de cette étude est de comparer les expositions moyennes à l’équilibre des 2 schémas d’administration : perfusion prolongée pendant 4 heures de Ceftolozane-Tazobactam à la posologie de 2 g trois fois par jour vs. perfusion courte en 1 heure de 2 g trois fois par jour.
    E.2.2Secondary objectives of the trial
    Compare the average exposition obtained with the current recommendations for the 2 products: ceftolozane and tazobactam
    Estimate the percentage of patients correctly exposed to the 2 products: ceftolozane and tazobactam
    Determine if Ceftolozane-Tazobactam 4-hours infusion is linked to an improved bacteriological progression in broncho-alveolar liquid
    Determine if Ceftolozane-Tazobactam 4-hours infusion is linked to an improved clinical progression
    Determine alveolar concentration of Ceftolozane-Tazobactam from a sample of the alveolar fluid produced by bronchial fibroscopy between the 24th hour and the 48th hour
    comparer l’exposition moyenne obtenue aux recommandations actuelles pour les 2 produits : ceftolozane et tazobactam
    estimer le pourcentage de patients correctement exposés aux 2 produits : ceftolozane et tazobactam
    déterminer si la perfusion prolongée de Ceftolozane-Tazobactam est associée à une meilleure évolution bactériologique dans le liquide broncho-alvéolaire par rapport à la perfusion courte
    déterminer si la perfusion prolongée de Ceftolozane-Tazobactam est associée à une meilleure évolution clinique par rapport à la perfusion courte.
    déterminer la concentration alvéolaire de Ceftolozane-Tazobactam à partir d’un prélèvement du liquide alvéolaire réalisé par fibroscopie bronchique entre la 24ème heure et la 48ème heure
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Age ≥ 18 years
    patients with ventilator associated-pneumonia to Pseudomonas aeruginosa
    patients hospitalized in intensive care units
    Pseudomonas aeruginosa susceptible to ceftolozane-tazobactam
    SAPS II (Simplified Acute. Physiological Score II) > 20
    Expected duration of survival > 7 days
    Informed consent of the patient or, failing that, the patient’s close or trustworthy person
    Affiliated to a social security scheme or equivalent
    Age ≥ 18 ans
    Patients hospitalisés en réanimation, sous ventilation artificielle, intubé ou trachéotomisé
    Infection nécessitant la mise sous Ceftolozane-Tazobactam
    Patient présentant une pneumonie acquise à l'hôpital, avec au moins 2 des critères suivants :
    température par sonde thermique > 38°C ou < 36°C,
    hyperleucocytose > 12 G/l ou leucopénie < 4 G/l
    dégradation du rapport PaO2/FiO2
    sécrétions bronchiques purulentes ou mucopurulentes,
    Et infiltrat radiologique pulmonaire parenchymateux diffus ou localisé, récent et persistant ou aggravation d'une image pulmonaire préexistante
    Associé à un prélèvement bactériologique avec soit LBA (positif si supérieur ou égal à 104), soit aspirations trachéales (positif si supérieur ou égal à 106).
    Pseudomonas aeruginosa sensible à l’association Ceftolozane-Tazobactam
    Consentement éclairé du patient ou, à défaut, du proche ou de la personne de confiance
    IGS II (Indice de Gravité Simplifié) > 20
    Durée attendue de survie > 7 jours
    Affilié à un régime de sécurité sociale ou équivalent
    E.4Principal exclusion criteria
    history of allergy to one of the two molecules
    history of allergy to betalactamines
    Strain Isolated resistant to Ceftolozane-Tazobactam combination
    Renal insufficiency with a glomerular filtration rate evaluated by CKD-EPI < 50 ml/min
    Patient on dialysis or under continuous hemodiafiltration
    Pregnant or nursing women
    Patient benefiting from a system of legal protection for adults
    Antécédents d’allergie à l’une des deux molécules, Ceftolozane et Tazobactam
    Antécédents d’allergie vraie aux bétalactamines (Pénicillines ou Céphalosporines)
    Isolement d’un germe résistant à l’association Ceftolozane-Tazobactam
    Insuffisance rénale avec un débit de filtration glomérulaire évalué par CKD-EPI < 50 ml/mn
    Patient dialysé ou sous hémodiafiltration continue
    Femmes enceintes ou allaitantes
    Patient bénéficiant d’un régime de protection juridique des majeurs
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the time that the concentration spends above 5*MIC, expressed as a percentage of the time interval between two administrations. The T>5*MIC will be determined for each patient from the concentration profile measured over an 8-hour post-administration interval. Since protein binding is low (<20%), the total concentration (sum of free form and plasma protein bound) will be used as a marker for free concentration. Therefore, the T>5*MIC will be calculated from the total concentrations. Our study will focus on only Pseudomonas aeruginosa PAVM with a critical MIC of 4 mg/l, T>5*MIC will then correspond to a residual serum concentration of 20 mg/l.
    Le critère principal de jugement est le T>5*CMI exprimé en pourcentage par rapport à l’intervalle de temps séparant deux administrations. Le T0-8h >5*CMI sera déterminé pour chaque patient à partir du profil de concentrations mesurées sur un intervalle de 8 heures post-administration. La fixation protéique étant faible (<20%), la concentration totale (somme de la forme libre et liée aux protéines plasmatiques) sera utilisée comme marqueur de la concentration libre. Par conséquent, le T>5*CMI sera calculé à partir des concentrations totales. Les bactéries les plus couramment rencontrées chez ces patients sont les entérobactéries (CMI critique 1 mg/l) et Pseudomonas aeruginosa (CMI critique 4 mg/l). Notre étude portera uniquement sur les PAVM à Pseudomonas aeruginosa dont la CMI critique est de 4 mg/l, T>5*CMI correspondra alors à une concentration sérique résiduelle de 20 mg/l pour le ceftolozane.
    E.5.1.1Timepoint(s) of evaluation of this end point
    For the pharmacokinetic study, 7 blood samples will be collected from 24 hours to 48 hours after the first ZERBAXA® administration.
    Pour l'étude pharmacocinétique, 7 prélèvements sanguins seront réalisés à partir de la 24e heure jusqu'à la 48e heure suivant la première administration de ZERBAXA.

    E.5.2Secondary end point(s)
    The percentage of patients with concentrations greater than 5*MIC over an 8-hour post administration interval
    Bactericidal rate obtained in vitro using the Hollow Fiber device. This rate is determined for broncho-alveolar concentrations estimated in patients with pneumonia acquired during ventilation,
    Bacteriological evaluation at the end of treatment and on day 15, based on actual bacteriological cure, presumed bacteriological cure, failure or bacterial superinfection to another germ.
    Percentage of patients recovering or failing at the end of the treatment period
    The number of days without artificial ventilation at D28,
    The duration of hospitalization,
    Survival at D28
    The alveolar concentration of Ceftolozane-Tazobactam from a sample of the alveolar fluid produced by bronchial fibroscopy between the 24th hour and the 48th hour.
    Pourcentage de patients présentant des concentrations supérieures à 5*CMI sur un intervalle de 8 heures post-administration
    Vitesse de bactéricidie obtenue in vitro à l’aide du dispositif Hollow Fiber après exposition aux concentrations broncho-alvéolaires estimées chez les patients traités pendant une durée correspondant à la période de traitement des patients
    Evaluation bactériologique en fin de traitement et à J15
    Pourcentage de patients en guérison ou échec à l’issue de la période de traitement
    Le nombre de jours sans ventilation artificielle à J28,
    La durée d’hospitalisation
    La survie à J28
    La concentration alvéolaire de Ceftolozane-Tazobactam à partir d’un prélèvement du liquide alvéolaire réalisé par fibroscopie bronchique entre la 24ème heure et la 48ème heure.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Depending on the secondary end points, the timepoints will occur:
    - Beetween the 24th hour and the 48th hour (after the beginning of the first infusion)
    - En fin de traitement (J7 à J10)
    - A J15
    - A J28
    Selon les objectifs secondaires, les critères seront évalués à différents moments:
    - Entre H24 et H48 (après le début de la première perfusion)
    - En fin de traitement (J7 à J10)
    - A J15
    - A J28
    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 No
    E.6.4Safety No
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    ZERBAXA (même produit) avec une durée de perfusion courte (1 heure)
    ZERBAXA (same product) with a short infusion (1 hour infusion)
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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
    Dernière visite dernier patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months
    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: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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
    Due to the inclusion criteria "Patients hospitalized in intensive care units", some patients will be incapable of giving their consent. In that case, the Informed consent will be given by the patient’s close or trustworthy person.
    Du fait du critère d'inclusion "Patients hospitalisés en réanimation", certains patients ne seront pas en mesure de donner leur consentement. Dans ce cas, le consentement éclairé sera donné par le proche ou la personne de confiance du patient.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state60
    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 Decision2018-06-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-25
    P. End of Trial
    P.End of Trial StatusOngoing
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