Clinical trial NCT06342115: Ceftolozane/Tazobactam Versus Meropenem for Febrile Neutropenia on Patients Colonized With or at Risk for Infection With Extended Spectrum Beta Lactamase - Producing Pathogens
Official title: Ceftolozane/Tazobactam Versus Meropenem for Febrile Neutropenia on Patients Colonized With or at Risk for Infection With Extended Spectrum Beta Lactamase (ESBL)-Producing Pathogens: a Randomized Double-blind Non-inferiority Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Febrile Neutropenia
Keywords: Febrile Neutropenia
Ceftolozane/tazobactam
ESBL
Meropenem
Lead sponsor: Beneficência Portuguesa de São Paulo
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2024-04-02
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study proposes a planned, double-blind, non-inferiority clinical trial involving patients with febrile neutropenia and risk of extended-spectrum beta-lactamase (ESBL) infection. The goal is:

- Analyze the efficacy and tolerability of Ceftolozane/tazobactam (CEF/TAZ) compared to the current standard of care (meropenem) in patients with febrile neutropenia and risk of ESBL infection.

Patients will be randomly assigned to receive CEF/TAZ or meropenem, with assessment of clinical response, toxicity and microbiological evolution. Stool samples will be collected before, during and after treatment for intestinal microbiota analysis and intestinal microbiome analysis to evaluate possible effects on GVHD. Analysis of the results will include the taxonomic classification of the organisms present. Data will be analyzed to assess non-inferiority in clinical response, incidence of GVHD, antimicrobial resistance and other outcomes.


Eligibility criteria: Inclusion criteria:

- Individuals who present with the onset of febrile neutropenia and at the same time present colonization with an ESBL-producing pathogen (identified through positive routine rectal swabs and/or positive culture of clinical specimen) or risk of infection with an ESBL-producing pathogen (use of 3rd/4th gen cephalosporin or piperacillin/tazobactam for at least 48 hours in the last 30 days).

Exclusion Criteria:

* Patients known to be colonized with carbapenem-resistant or CEF/TAZ-resistant pathogens
* Patients with previous use of carbapenems for at least 48h in the past 30 days are also excluded due to risk of resistance to the study drugs.
* Growth of a pathogen resistant to either study drug in a relevant clinical specimen during the intervention phase will be followed by adjustment of therapy according to local protocol, unblinding, and exclusion from the study.
* Patients that have received less than 72h of either study drug will also be excluded from the final analyses.

Primary outcomes:
measure: Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Intent-to-Treat (ITT) Population
timeFrame: Within 24 hours after last dose of study drug (Up to ~Day 15)
Secondary outcomes:
measure: Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Microbiological Intent-to-Treat (mITT) Population
timeFrame: 7 to 14 days after last dose of study drug (Up to ~Day 30)
measure: Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Intent-to-Treat (ITT) Population
timeFrame: 7 to 14 days after last dose of study drug (Up to ~Day 30)
measure: Incidence of microbiologically documented infections and identification of causative organisms in culture
timeFrame: Up to 100 days
measure: In-hospital mortality
timeFrame: Until100 days after allogenic HSCT
measure: Occurrence of graft versus host disease (GVHD)
timeFrame: Until100 days after allogenic HSCT
measure: Frequency of multidrug resistant-pathogen infections or colonization
timeFrame: Until100 days after allogenic HSCT
measure: Faecal microbiota analysis
timeFrame: Up to 100 days
measure: Percentage of Participants Who Report 1 or More Adverse Event (AE)
timeFrame: Up to 35 days after last dose of study drug
measure: Percentage of Participants With Any Serious Adverse Event (SAE)
timeFrame: Up to 35 days after last dose of study drug (Up to ~Day 50) ]
measure: Percentage of Participants Discontinuing Study Drug Due to an Adverse Event (AE)
timeFrame: Up to 14 days after the first dose of study drug (Up to ~Day 15)
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: A Beneficência Portuguesa de São Paulo
Study officials:
affiliation: A Beneficência Portuguesa de São Paulo
name: João Prats, MD
role: PRINCIPAL_INVESTIGATOR
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