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

April 30, 2025 updated by: João Antonio Gonçalves Garreta Prats, Beneficência Portuguesa de São Paulo

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

176

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Research Department
  • Phone Number: +55 11 3505 5031
  • Email: naipe@bp.org.br

Study Contact Backup

Study Locations

  • Brazil
      • São Paulo, Brazil
        • Recruiting
        • A Beneficência Portuguesa de São Paulo
        • Contact:
          • João Prats, MD
          • Phone Number: +55 11 3505 5031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention

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
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.
Active Comparator: Control

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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Intent-to-Treat (ITT) Population
Time Frame: Within 24 hours after last dose of study drug (Up to ~Day 15)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Discontinuing Study Drug Due to an Adverse Event (AE)
Time Frame: Up to 14 days after the first dose of study drug (Up to ~Day 15)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Up to 14 days after the first dose of study drug (Up to ~Day 15)
Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Microbiological Intent-to-Treat (mITT) Population
Time Frame: 7 to 14 days after last dose of study drug (Up to ~Day 30)
To compare the clinical response rates at the EOT visit for ceftolozane/tazobactam versus meropenem in the Microbiological Intent-to-Treat (mITT) Population. 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.
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
Time Frame: 7 to 14 days after last dose of study drug (Up to ~Day 30)
To demonstrate the non-inferiority of ceftolozane/tazobactam versus meropenem in participants with Febrile Neutropenia on Patients Colonized With or at Risk for Infection With Extended Spectrum Beta Lactamase - Producing Pathogens at the TOC visit (7 to 14 days after the end-of-therapy [EOT] visit) using a non-inferiority margin of 12.5%. Clinical response at the TOC visit was defined as cure (complete resolution of fever and symptoms related to Febrile Neutropenia), 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 unless the clinical outcome at the EOT visit was failure.
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
Time Frame: Up to 100 days
The incidences of microbiologically documented infections, along with the identification of causative organisms in culture, will be recorded. The measure will be assessed through the counting of cases confirmed by positive cultures.
Up to 100 days
In-hospital mortality
Time Frame: Until100 days after allogenic HSCT
In-hospital mortality in the first 100 days after allogenic hematopoietic stem cell transplant (HSCT)
Until100 days after allogenic HSCT
Occurrence of graft versus host disease (GVHD)
Time Frame: Until100 days after allogenic HSCT
Occurrence of GVHD In the first 100 days after allogenic HSCT
Until100 days after allogenic HSCT
Frequency of multidrug resistant-pathogen infections or colonization
Time Frame: Until100 days after allogenic HSCT
Frequency of multidrug resistant-pathogen infections or colonization by weekly rectal swab screening
Until100 days after allogenic HSCT
Faecal microbiota analysis
Time Frame: Up to 100 days
Patients will also undergo faecal microbiota analysis on baseline and at the end of therapy as a surrogate marker for future GVHD.
Up to 100 days
Percentage of Participants Who Report 1 or More Adverse Event (AE)
Time Frame: Up to 35 days after last dose of study drug
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Up to 35 days after last dose of study drug
Percentage of Participants With Any Serious Adverse Event (SAE)
Time Frame: Up to 35 days after last dose of study drug (Up to ~Day 50) ]
A serious adverse event (SAE) is an AE that results in death, is life threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment.
Up to 35 days after last dose of study drug (Up to ~Day 50) ]

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beneficência Portuguesa de São Paulo

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: João Prats, MD, A Beneficência Portuguesa de São Paulo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

February 29, 2024

First Submitted That Met QC Criteria

March 28, 2024

First Posted (Actual)

April 2, 2024

Study Record Updates

Last Update Posted (Actual)

May 2, 2025

Last Update Submitted That Met QC Criteria

April 30, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLEMENT TRIAL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Febrile Neutropenia

Clinical Trials on Ceftolozane-Tazobactam

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovakia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe