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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

NCT05565222 · Status: RECRUITING · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 600

Last updated 2023-04-18

No results posted yet for this study

Summary

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.

Conditions

Interventions

DRUG

Piperacillin/tazobactam or temocillin

Piperacillin/tazobactam : 4.5 g by intravenous route every 6 hours (adjusted in case of renal failure). Temocillin : 6g/24 hours infused continuously by intravenous route after 2 g loading dose (adjusted in case of renal failure)

DRUG

Meropenem

2 g every 8 hours by intravenous route (adjusted in case of renal failure)

Sponsors & Collaborators

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2023-03-11
Primary Completion
2026-04-30
Completion
2026-06-30

Countries

  • France

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05565222 on ClinicalTrials.gov