Informations générales (source: ClinicalTrials.gov)
Piperacillin-tazobactam and Temocillin as Carbapenem-alternatives for the Treatment of Severe Infections Due to Extended-spectrum Beta-lactamase-Producing Gram-negative Enterobacteriaceae in the Intensive Care Unit (PITAGORE)
Interventional
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
mars 2023
juin 2026
29 juin 2024
Infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae
are a major public health concern, in particular in the intensive care unit (ICU), due to
the increase in their incidence. Carbapenems are the treatment of choice of these
infections, but their increased use may select for carbapenem resistance in Gram-negative
bacilli, which currently represents the greatest threat in terms of antibiotic
resistance. Several retrospective studies have shown that the use of non-carbapenem
antibiotics (mainly the association of piperacillin/tazobactam, but also cefepime and
temocillin) may be safe alternatives to carbapenems to treat these pathogens when the
strain is susceptible to the corresponding antibiotic. However, one recent randomized
controlled study, the Merino trial, failed to demonstrate the non-inferiority of
piperacillin/tazobactam, as compared to meropenem, in patients with Gram-negative bacilli
bacteremia resistant to third generation cephalosporins (mainly ESBL producers). However,
the patients included in that study were not ICU patients, dosing and modalities of
piperacillin/tazobactam administration were not optimal (30-min infusion whereas 4-hours
infusion may be associated with better outcome), and cause of death of patients in the
piperacillin/tazobactam arm were not due to antimicrobial treatment failure (mostly death
due to care withdrawal in cancer patients). Recently, a retrospective bicenter study
performed in ICU patients showed that outcome of patients with severe infection (i.e.
sepsis and septic shock according to the Sepsis-3 definition) due to ESBL-producing
Enterobacteriaceae susceptible to non-carbapenem agents treated with a non-carbapenem
agent was similar to that of patients treated with carbapenems.
Given the scarcity of data in ICU patients, the disputable results of the Merino trial,
we will therefore conduct a multicenter, randomized, open-label trial of non-carbapenem
beta-lactam (piperacillin/tazobactam or temocillin) treatment vs. meropenem treatment for
ESBL-producing Enterobaceriaceae severe infection in ICU patients. Our hypothesis is that
a non-carbapenem beta-lactam treatment is non-inferior to carbapenem treatment in
patients with ESBL-producing Enterobacteriaceae severe infection in the ICU.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Avicenne | LUYT Charles-edouard | 18/04/2025 07:55:46 | Contacter | ||
| AP-HP - Hôpital Cochin | LUYT Charles-edouard | 18/04/2025 07:55:46 | Contacter | ||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | LUYT Charles-edouard | 18/04/2025 07:55:46 | Contacter | ||
| AP-HP - Hôpital La Pitié-Salpêtrière | LUYT Charles-edouard | 18/04/2025 07:55:46 | Contacter | ||
| AP-HP - Hôpital Louis Mourier | LUYT Charles-edouard | 18/04/2025 07:55:46 | Contacter | ||
| HOPITAL FOCH | CHARLES CERF | 28/04/2025 16:00:03 | Contacter | ||
| HOPITAL NOVO | RADJOU Aguila | 14/02/2025 09:03:19 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| LUYT Charles -Edouard - 75013 - Paris - France | LUYT Charles -Edouard, MD | Contact (sur clinicalTrials) | |||
| MAYAUX Julien - 75013 - Paris - France | MAYAUX Julien, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Patients ≥ 18-year-old
- Hospitalized in the ICU
- Severe infection, eg sepsis or septic shock (according to the Sepsis-3 definition)
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated
host response to infection, characterized by an increase of Sequential Organ Failure
Assessment (SOFA) score of 2 points or more. This increase in 2 points will be
calculated the day infection is diagnosed (day of positive culture serving as
reference for the infection) as compared to the day before infection onset.
Septic shock is defined as sepsis and persisting hypotension requiring vasopressors to
maintain mean arterial pressure ≥65 mmHg and having a serum lactate level >2 mmol/l
despite adequate volume resuscitation.
This criterion (sepsis or septic shock) has to be fulfilled within a time frame of +/- 24
hours from the day of infection diagnosis (i.e. the day of positive bacteriological
sample).
- 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)
- 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
- Affiliation to social security (AME excluded)
- Patients ≥ 18-year-old
- Hospitalized in the ICU
- Severe infection, eg sepsis or septic shock (according to the Sepsis-3 definition)
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated
host response to infection, characterized by an increase of Sequential Organ Failure
Assessment (SOFA) score of 2 points or more. This increase in 2 points will be
calculated the day infection is diagnosed (day of positive culture serving as
reference for the infection) as compared to the day before infection onset.
Septic shock is defined as sepsis and persisting hypotension requiring vasopressors to
maintain mean arterial pressure ≥65 mmHg and having a serum lactate level >2 mmol/l
despite adequate volume resuscitation.
This criterion (sepsis or septic shock) has to be fulfilled within a time frame of +/- 24
hours from the day of infection diagnosis (i.e. the day of positive bacteriological
sample).
- 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)
- 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
- Affiliation to social security (AME excluded)
- Pregnancy or breastfeeding
- Known allergy to beta-lactam
- Patient with severe neutropenia, as defined by absolute neutrophil count <0.5x109/L
- Infection requiring prolonged antimicrobial treatment (endocarditis; mediastinitis;
osteomyelitis/septic arthritis; undrainable/undrained abscess; unremovable/unremoved
prosthetic-associated infection)
- Moribund, defined by a SAPS II score at inclusion >75
- Decision of withholding/withdrawing care
- Patient with concomitant infection requiring antibiotics with activity against
Gram-negative bacilli, including patient with polymicrobial infection with pathogen
resistant to study drugs
- Participation in another interventional study evaluating drugs or being in the
exclusion period at the end of a previous study evaluating drugs .
- Hypersensitivity to any components of the formulations