Ceftolozane/Tazobactam Versus Meropenem for Febrile Neutropenia on Patients Colonized With or at Risk for Infection With Extended Spectrum Beta Lactamase - Producing Pathogens

NCT06342115 | Recruiting Phase 4

• 1 other identifier: CLEMENT TRIAL
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 1

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.

Conditions

Febrile Neutropenia

Keywords

Febrile Neutropenia; Ceftolozane/tazobactam; ESBL; Meropenem

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Intent-to-Treat (ITT) Population

  To compare the clinical response rates at the EOT visit for ceftolozane/tazobactam versus meropenem. Clinical response at the EOT visit was defined as cure (complete resolution of fever and symptoms related to Febrile Neutropenia episode), failure (non-resolution, relapse or recurrence of Febrile Neutropenia) or indeterminate (no evaluable study data). A favorable clinical response is a clinical cure. A missing clinical response will be considered indeterminate.

  Within 24 hours after last dose of study drug (Up to ~Day 15)

Secondary Outcomes (10)

• Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Microbiological Intent-to-Treat (mITT) Population

  7 to 14 days after last dose of study drug (Up to ~Day 30)

• Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Intent-to-Treat (ITT) Population

  7 to 14 days after last dose of study drug (Up to ~Day 30)

• Incidence of microbiologically documented infections and identification of causative organisms in culture

  Up to 100 days

• In-hospital mortality

  Until100 days after allogenic HSCT

• Occurrence of graft versus host disease (GVHD)

  Until100 days after allogenic HSCT

Study Arms (2)

Intervention

EXPERIMENTAL

In the intervention arm 3g of ceftolozane-tazobactam are given intravenously every 8 hours. Duration of therapy should follow local guidelines and de-escalation is allowed after identification of causative pathogens. Colonized patients will be considered those identified through positive routine rectal swabs and/or positive culture of a clinical sample) or at risk of infection by an ESBL-producing pathogen due to use of 3rd/4th gen cephalosporin or piperacillin/tazobactam for at least 48 hours. in the last 30 days.

Drug: Ceftolozane-Tazobactam

Control

ACTIVE COMPARATOR

The comparator arm consists of 2g of meropenem given intravenously every 8 hours.Duration of therapy should follow local guidelines and de-escalation is allowed after identification of causative pathogens. Colonized patients will be considered those identified through positive routine rectal swabs and/or positive culture of a clinical sample) or at risk of infection by an ESBL-producing pathogen due to use of 3rd/4th gen cephalosporin or piperacillin/tazobactam for at least 48 hours. in the last 30 days.

Drug: Meropenem

Interventions

Ceftolozane-Tazobactam DRUG

In the intervention arm 3g of ceftolozane-tazobactam are given intravenously every 8 hours. Duration of therapy should follow local guidelines and de-escalation is allowed after identification of causative pathogens.

Intervention

Meropenem DRUG

The comparator arm consists of 2g of meropenem given intravenously every 8 hours.Duration of therapy should follow local guidelines and de-escalation is allowed after identification of causative pathogens.

Control

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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).

You may not qualify if:

• 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.
• Patients that have received less than 72h of either study drug will also be excluded from the final analyses.

Sponsors & Collaborators

• Beneficência Portuguesa de São Paulo: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

A Beneficência Portuguesa de São Paulo

São Paulo, Brazil

RECRUITING

Related Publications (16)

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MeSH Terms

Conditions

Febrile Neutropenia

Interventions

ceftolozane, tazobactam drug combination; Meropenem

Condition Hierarchy (Ancestors)

Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• João Prats, MD

  A Beneficência Portuguesa de São Paulo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Department

CONTACT

+55 11 3505 5031; naipe@bp.org.br

Bianca Verboski

CONTACT

bianca.verboski@bp.org.br

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: April 2, 2024
• Study Start: March 26, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)