Clinical trial • Phase III • Infectious Disease
piperacillin sodium, tazobactam sodium for Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae severe infection
Phase III trial of piperacillin sodium, tazobactam sodium for Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae severe infection.
Overview
- Trial Therapeutic Area
- Infectious Disease
- Trial Disease
- Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae severe infection
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 18-09-2024
- First CTIS Authorization Date
- 27-09-2024
Trial design
Randomised, carbapenem comparator: meropenem (meropenem arrow 1 g, solution for injection/infusion) versus carbapenem-sparing agents: piperacillin and beta-lactamase inhibitor (piperacillin/tazobactam, infusion) or temocillin (negaban 2 g, infusion). dose/schedule details not specified in the ctis summary.-controlled Phase III trial in France.
- Randomised
- Yes
- Comparator
- Carbapenem comparator: MEROPENEM (MEROPENEM ARROW 1 g, solution for injection/infusion) versus carbapenem-sparing agents: PIPERACILLIN AND BETA-LACTAMASE INHIBITOR (piperacillin/tazobactam, infusion) or TEMOCILLIN (NEGABAN 2 g, infusion). Dose/schedule details not specified in the CTIS summary.
- Target Sample Size
- 600
- Trial Duration For Participant
- 90
Eligibility
Recruits 600 Signed Informed consent from patient/a legal representative/a family member/a close relative. According to the specifications of emergency inclusion, randomization without the close relative or surrogate consent could be performed if the patient is unable to give his/her consent and when the legal representative/family member or close relative are absent except patients included in another study for which emergency inclusion has already been used (see exclusion criteria n° 8). For these patients, emergency inclusion cannot be used) close relative/surrogate/family consent will be asked as soon as possible. The patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow.
- Pregnancy Exclusion
- Pregnancy or breastfeeding
- Vulnerable Population
- Signed Informed consent from patient/a legal representative/a family member/a close relative. According to the specifications of emergency inclusion, randomization without the close relative or surrogate consent could be performed if the patient is unable to give his/her consent and when the legal representative/family member or close relative are absent except patients included in another study for which emergency inclusion has already been used (see exclusion criteria n° 8). For these patients, emergency inclusion cannot be used) close relative/surrogate/family consent will be asked as soon as possible. The patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow
Inclusion criteria
- {"criterion_text":"- Patients ≥ 18-year-old\n- Hospitalized in the ICU\n- Severe infection, eg infection in patient hospitalized in ICU with or without sepsis or septic shock (according to the Sepsis-3 definition) If present sepsis or septic shock have to be fulfilled within a time frame of +/- 24 hours from the day of infection diagnosis (i.e. the day of positive bacteriological sample).\n- Pathogen responsible for infection is an ESBL-producing Enterobacteriaceae susceptible to meropenem and either to piperacillin/tazobactam (minimum inhibitory concentration <8 mg/L) or to temocillin (minimum inhibitory concentration ≤8 mg/L)\n- Signed Informed consent from patient/a legal representative/a family member/a close relative. According to the specifications of emergency inclusion, randomization without the close relative or surrogate consent could be performed if the patient is unable to give his/her consent and when the legal representative/family member or close relative are absent except patients included in another study for which emergency inclusion has already been used (see exclusion criteria n° 8). For these patients, emergency inclusion cannot be used) close relative/surrogate/family consent will be asked as soon as possible. The patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow\n- Affiliation to social security (AME excluded)"}
Exclusion criteria
- {"criterion_text":"- Pregnancy or breastfeeding\n- Known allergy to beta-lactam\n- Patient with severe neutropenia, as defined by absolute neutrophil count <0.5x109/L\n- Infection requiring prolonged antimicrobial treatment (endocarditis; mediastinitis; osteomyelitis/septic arthritis; undrainable/undrained abscess; unremovable/unremoved prosthetic-associated infection)\n- Moribund, defined by a SAPS II score at inclusion >75\n- Decision of withholding/withdrawing care\n- Patient with concomitant infection requiring antibiotics with activity against Gram-negative bacilli, including patient with polymicrobial infection with pathogen resistant to study drugs\n- Participation in another interventional study evaluating drugs or being in the exclusion period at the end of a previous study evaluating drugs.\n- Hypersensitivity to any components of the formulations"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Mortality at 30 days from the date of randomization","definition_or_measurement_approach":"La mortalité à 30 jours après la date de randomisation. (Mortality at 30 days after the date of randomization)"}
Secondary endpoints
- {"endpoint_text":"- 90-day mortality rate.","definition_or_measurement_approach":""}
- {"endpoint_text":"- Relapse rates of ESBL infection at day 30.","definition_or_measurement_approach":""}
- {"endpoint_text":"- Clinical failure rate at day 30 (relapse of ESBL infection or death between randomization and day 30).","definition_or_measurement_approach":""}
- {"endpoint_text":"- Rate of antibiotic allergy at day 30.","definition_or_measurement_approach":""}
- {"endpoint_text":"- Rate of adverse events at day 30,","definition_or_measurement_approach":""}
- {"endpoint_text":"- ICU length of stay","definition_or_measurement_approach":""}
- {"endpoint_text":"- Hospital length of stay","definition_or_measurement_approach":""}
- {"endpoint_text":"- ICU-free days at day 30","definition_or_measurement_approach":""}
- {"endpoint_text":"- Hospital-free days at day 30","definition_or_measurement_approach":""}
- {"endpoint_text":"- Antibiotic-free days at day 30","definition_or_measurement_approach":""}
- {"endpoint_text":"- Kinetics of organ failure from randomization to day 30 post-randomization, assessed by the sequential organ failure assessment (SOFA) score and its components","definition_or_measurement_approach":"Assessed by the Sequential Organ Failure Assessment (SOFA) score and its components"}
- {"endpoint_text":"- Rate of faecal colonization with carbapenem-resistant Gram-negative bacilli at end of treatment, ICU discharge and day 90","definition_or_measurement_approach":""}
- {"endpoint_text":"- Rate of Clostridium difficile infection at day 90.","definition_or_measurement_approach":""}
- {"endpoint_text":"- Rate of secondary nosocomial infection at day 90","definition_or_measurement_approach":""}
- {"endpoint_text":"- Proportion of patients in whom duration of antimicrobial treatment of the index episode (the episode that led to inclusion in the study) has been exceeded compared to the recommended duration.","definition_or_measurement_approach":""}
- {"endpoint_text":"- Proportion of patients who change their treatment before the recommended duration without relapse (= cross-over)","definition_or_measurement_approach":""}
Recruitment
- Planned Sample Size
- 600
- Recruitment Window Months
- 57
- Consent Approach
- Signed Informed consent from patient/a legal representative/a family member/a close relative. According to the specifications of emergency inclusion, randomization without the close relative or surrogate consent could be performed if the patient is unable to give his/her consent and when the legal representative/family member or close relative are absent except patients included in another study for which emergency inclusion has already been used (see exclusion criteria n° 8). For these patients, emergency inclusion cannot be used) close relative/surrogate/family consent will be asked as soon as possible. The patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow. Subject information and informed consent form documents listed in CTIS (examples: L1_SIS-ICF_NIFC-patient_PITAGORE; L1_SIS-ICF_NIFC-fam-pc-proche_PITAGORE; L1_SIS-ICF_NINO-utilisation-donnees_PITAGORE).
Geography
- Total Number Of Sites
- 31
- Total Number Of Participants
- 600
France
- Earliest CTIS Part Ii Submission Date
- 10-06-2024
- Latest Decision Or Authorization Date
- 08-04-2026
- Processing Time Days
- 667
- Number Of Sites
- 31
- Number Of Participants
- 600
Sites
- Site Name
- Centre Hospitalier General
- Department Name
- Service de Réanimation Polyvalente
- Principal Investigator Name
- Mohamed GHALAYINI
- Principal Investigator Email
- mohamed.ghalayini@ch-gonesse.fr
- Contact Person Name
- Mohamed GHALAYINI
- Contact Person Email
- mohamed.ghalayini@ch-gonesse.fr
- Site Name
- Groupe Hospitalier Du Sud Ile De France
- Department Name
- Service de Réanimation Médico-Chirurgicale
- Principal Investigator Name
- Shidasp SIAMI
- Principal Investigator Email
- shidasp.siami@ch-sudessonne.fr
- Contact Person Name
- Shidasp SIAMI
- Contact Person Email
- shidasp.siami@ch-sudessonne.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service de Réanimation Chirurgicale Polyvalente
- Principal Investigator Name
- Antoine MONSEL
- Principal Investigator Email
- antoine.monsel@aphp.fr
- Contact Person Name
- Antoine MONSEL
- Contact Person Email
- antoine.monsel@aphp.fr
- Site Name
- Groupe Hospitalier De La Region De Mulhouse Et Sud Alsace
- Department Name
- Service de soin intentifs
- Principal Investigator Name
- Joy MOOTIEN
- Principal Investigator Email
- mootien@ghrmsa.fr
- Contact Person Name
- Joy MOOTIEN
- Contact Person Email
- mootien@ghrmsa.fr
- Site Name
- Centre Hospitalier General De St Denis
- Department Name
- Service de Médecine Intensive et réanimation
- Principal Investigator Name
- Nolan HASSOLD-RUGOLINO
- Principal Investigator Email
- nolan.hassold@ch-stdenis.fr
- Contact Person Name
- Nolan HASSOLD-RUGOLINO
- Contact Person Email
- nolan.hassold@ch-stdenis.fr
- Site Name
- Centre Hospitalier Intercom Gregoire
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Vincent DAS
- Principal Investigator Email
- vincent.das@chi-andre-gregoire.fr
- Contact Person Name
- Vincent DAS
- Contact Person Email
- vincent.das@chi-andre-gregoire.fr
- Site Name
- Centre Hospitalier Intercommunal De Poissy Saint Germain
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Claire PICHEREAU
- Principal Investigator Email
- claire.pichereau@ght-yvelinesnord.fr
- Contact Person Name
- Claire PICHEREAU
- Contact Person Email
- claire.pichereau@ght-yvelinesnord.fr
- Site Name
- Centre Hospitalier Victor Dupouy
- Department Name
- Médecine Intensive-Réanimation
- Principal Investigator Name
- Florent BAVOZET
- Principal Investigator Email
- fbavozet@ch-dreux.fr
- Contact Person Name
- Florent BAVOZET
- Contact Person Email
- fbavozet@ch-dreux.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Julien MAYAUX
- Principal Investigator Email
- julien.mayaux@aphp.fr
- Contact Person Name
- Julien MAYAUX
- Contact Person Email
- julien.mayaux@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Luc HAUDEBOURG
- Principal Investigator Email
- luc.haudebourg@aphp.fr
- Contact Person Name
- Luc HAUDEBOURG
- Contact Person Email
- luc.haudebourg@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Charles Edouard LUYT
- Principal Investigator Email
- charles-edouard.luyt@aphp.fr
- Contact Person Name
- Charles Edouard LUYT
- Contact Person Email
- charles-edouard.luyt@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation médicochirurgicale
- Principal Investigator Name
- Sophie NAGLE
- Principal Investigator Email
- sophie.nagle@aphp.fr
- Contact Person Name
- Sophie NAGLE
- Contact Person Email
- sophie.nagle@aphp.fr
- Site Name
- Centre Hospitalier Universitaire D Orleans
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- François BARBIER
- Principal Investigator Email
- francois.barbier@chr-orleans.fr
- Contact Person Name
- François BARBIER
- Contact Person Email
- francois.barbier@chr-orleans.fr
- Site Name
- Hospital Foch
- Department Name
- Service de Réanimation
- Principal Investigator Name
- Charles CERF
- Principal Investigator Email
- c.cerf@hopital-foch.org
- Contact Person Name
- Charles CERF
- Contact Person Email
- c.cerf@hopital-foch.org
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Keyvan RAZAZI
- Principal Investigator Email
- keyvan.razazi@aphp.fr
- Contact Person Name
- Keyvan RAZAZI
- Contact Person Email
- keyvan.razazi@aphp.fr
- Site Name
- Centre Hospitalier Et Universitaire De Limoges
- Department Name
- Réanimation polyvalente
- Principal Investigator Name
- Julien VAIDIE
- Principal Investigator Email
- julien.vaidie@chu-limoges.fr
- Contact Person Name
- Julien VAIDIE
- Contact Person Email
- julien.vaidie@chu-limoges.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service d’Anesthésie-Réanimation
- Principal Investigator Name
- Adrien BOUGLE
- Principal Investigator Email
- adrien.bougle@aphp.fr
- Contact Person Name
- Adrien BOUGLE
- Contact Person Email
- adrien.bougle@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Julien CHARPENTIER
- Principal Investigator Email
- julien.charpentier@aphp.fr
- Contact Person Name
- Julien CHARPENTIER
- Contact Person Email
- julien.charpentier@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Lille
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Saad NSEIR
- Principal Investigator Email
- s-nseir@chru-lille.fr
- Contact Person Name
- Saad NSEIR
- Contact Person Email
- s-nseir@chru-lille.fr
- Site Name
- Centre Hospitalier Departemental Vendee
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Christine LEBERT
- Principal Investigator Email
- christine.lebert@ght85.fr
- Contact Person Name
- Christine LEBERT
- Contact Person Email
- christine.lebert@ght85.fr
- Site Name
- Centre Hospitalier Le Mans
- Department Name
- Réanimation Médico-Chirurgicale
- Principal Investigator Name
- Cédric DARREAU
- Principal Investigator Email
- cdarreau@ch-lemans.fr
- Contact Person Name
- Cédric DARREAU
- Contact Person Email
- cdarreau@ch-lemans.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Damien ROUX
- Principal Investigator Email
- damien.roux@aphp.fr
- Contact Person Name
- Damien ROUX
- Contact Person Email
- damien.roux@aphp.fr
- Site Name
- Centre Hospitalier Sud Francilien
- Department Name
- Service de Réanimation Polyvalente
- Principal Investigator Name
- Danielle REUTER
- Principal Investigator Email
- danielle.reuter@chsf.fr
- Contact Person Name
- Danielle REUTER
- Contact Person Email
- danielle.reuter@chsf.fr
- Site Name
- Centre Hospitalier De Versailles
- Department Name
- Service de Réanimation Médico-Chirurgicale
- Principal Investigator Name
- Candice FONTAINE
- Principal Investigator Email
- cfontaine@ght78sud.fr
- Contact Person Name
- Candice FONTAINE
- Contact Person Email
- cfontaine@ght78sud.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Anesthésie réanimation
- Principal Investigator Name
- Natacha KAPANDJI
- Principal Investigator Email
- natacha.kapandji@aphp.fr
- Contact Person Name
- Natacha KAPANDJI
- Contact Person Email
- natacha.kapandji@aphp.fr
- Site Name
- Centre Hospitalier Bethune Beuvry
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Ghada SBOUDI SOLTANI
- Principal Investigator Email
- gsboui@ch-bethune.fr
- Contact Person Name
- Ghada SBOUDI SOLTANI
- Contact Person Email
- gsboui@ch-bethune.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service d’Anesthésie-Réanimation
- Principal Investigator Name
- Florian BLANCHARD
- Principal Investigator Email
- florian.blanchard@aphp.fr
- Contact Person Name
- Florian BLANCHARD
- Contact Person Email
- florian.blanchard@aphp.fr
- Site Name
- Centre Hospitalier Le Mans
- Department Name
- Réanimation Médico-Chirurgicale
- Principal Investigator Name
- Cédric DARREAU
- Principal Investigator Email
- cdarreau@ch-lemans.fr
- Contact Person Name
- Cédric DARREAU
- Contact Person Email
- cdarreau@ch-lemans.fr
- Site Name
- Centre Hospitalier Bretagne Atlantique
- Department Name
- Service de Réanimation Polyvalente
- Principal Investigator Name
- Florian REIZINE
- Principal Investigator Email
- florian.reizine@ch-bretagne-atlantique.fr
- Contact Person Name
- Florian REIZINE
- Contact Person Email
- florian.reizine@ch-bretagne-atlantique.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Médecine Intensive Réanimation
- Principal Investigator Name
- Eric MAURY
- Principal Investigator Email
- eric.maury@aphp.fr
- Contact Person Name
- Eric MAURY
- Contact Person Email
- eric.maury@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Poitiers
- Department Name
- Service de Réanimation Chirurgicale
- Principal Investigator Name
- Nathan FERRAND
- Principal Investigator Email
- Nathan.ferrand@chu-poitiers.fr
- Contact Person Name
- Nathan FERRAND
- Contact Person Email
- Nathan.ferrand@chu-poitiers.fr
Sponsor
Primary sponsor
- Full Name
- Assistance Publique Hopitaux De Paris
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- France
Investigational products
- Investigational Product Name
- PIPERACILLIN AND BETA-LACTAMASE INHIBITOR
- Active Substance
- piperacillin sodium, tazobactam sodium
- Modality
- Small molecule
- Routes Of Administration
- INFUSION
- Route
- INFUSION
- Authorisation Status
- Authorised (prodAuthStatus=2)
- Maximum Dose
- 2 g (maxDailyDoseAmount 2 g)
- Investigational Product Name
- NEGABAN (TEMOCILLIN)
- Active Substance
- temocillin sodium
- Modality
- Small molecule
- Routes Of Administration
- INFUSION
- Route
- INFUSION
- Authorisation Status
- Authorised (prodAuthStatus=2)
- Maximum Dose
- 8 g (maxDailyDoseAmount 8 g)
- Investigational Product Name
- MEROPENEM ARROW
- Active Substance
- meropenem anhydrous
- Modality
- Small molecule
- Routes Of Administration
- INFUSION
- Route
- INFUSION
- Authorisation Status
- Authorised (prodAuthStatus=2)
- Maximum Dose
- 6 g (maxDailyDoseAmount 6 g)
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