Antimicrobial Revision in Persistent Febrile Neutropenia

May 15, 2024 updated by: Wake Forest University Health Sciences

Antimicrobial Revision in Patients With Persistent Febrile Neutropenia: A Prospective, Randomized Trial

Febrile neutropenia is often seen in patients with hematologic malignancies who receive cytotoxic chemotherapy. These patients are usually placed on posaconazole prophylaxis upon starting chemotherapy. If an episode of febrile neutropenia occurs, generally an anti-pseudomonal beta lactam, like cefepime or piperacillin-tazobactam, is initiated. In patients who continue to fever on these agents, the optimal method of antimicrobial revision has yet to be determined.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In this prospective, randomized, open-label, single-center trial, the primary objective is to compare the clinical efficacy of two approaches to antimicrobial revision among patients with persistent febrile neutropenia. Neutropenic patients on cefepime or piperacillin-tazobactam who continue to fever for greater than 96 hours will be randomized to receive either meropenem or micafungin dosed according to local guidelines. The primary outcome is a global success rate including a composite of defervescence within 72 hours of meropenem or micafungin initiation, absence of signs or symptoms of infection, and no modification to antimicrobial regimen after initiation of meropenem or micafungin. The secondary outcomes to be collected include in-hospital mortality or discharge to hospice, hospital length of stay, time to defervescence, days of therapy of meropenem or micafungin, rate of Clostridioides difficile infection on meropenem or micafungin, and cause of any proven breakthrough infection while on meropenem or micafungin.

Study Type

Interventional

Enrollment (Estimated)

120

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

Study Contact Backup

Study Locations

  • United States
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Contact:

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ≥ 18 years of age
  • Diagnosis of hematologic malignancy
  • Receiving chemotherapy as treatment of hematologic malignancy
  • Neutropenia defined as an absolute neutrophil count (ANC) ≤ 500 cells/mm3 or an ANC ≤ 1000 cells/mm3 with a predicted decline to < 500 cells/mm3 within 48 hours
  • Prescribed cefepime or piperacillin-tazobactam as initial treatment for febrile neutropenia
  • Persistent fever for ≥ 96 hours since initiation of cefepime or piperacillin-tazobactam OR recurrent fever that occurs ≥ 96 hours since initiation of cefepime or piperacillin-tazobactam (fever defined as single temperature of ≥ 38.3°C (101°F) or a temperature of ≥ 38°C (100.4°F) on two consecutive measures separated by at least one hour)
  • Receipt of posaconazole as neutropenia prophylaxis for at least 3 calendar days

Exclusion Criteria:

  • Clinically or microbiologically confirmed infection at time of enrollment, For example, a positive culture or rapid diagnostic test, positive imaging (X-ray, CT, MRI) or biomarker, such as galactomannan, that is consistent with infection
  • History of infection with organism known to be resistant to meropenem or micafungin
  • Documented allergy to carbapenems or echinocandins
  • Concomitant use of valproic acid
  • Uncontrolled seizure disorder
  • Pregnancy
  • Previous enrollment in this study

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Meropenem Arm
Patients who meet inclusion criteria may be randomized to meropenem (routine standard of care) dose according to local dosing guidelines to include the use of extended-infusions and adjustments to account for renal function. Duration will be managed by the primary team.
Drug: Meropenem
Carbapenem antibiotic
Other Names:
  • Merrem
Active Comparator: Micafungin Arm
Patients who meet inclusion criteria may be randomized to micafungin dosed as 150mg intravenously every 24 hours according to local dosing guidelines. Duration will be managed by the primary team.
Drug: Micafungin
Echinocandin antifungal
Other Names:
  • Mycamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Global Success Rate
Time Frame: Hour 72

Percentage of study candidates who meet all of the following criteria:

  • Defervescence, as defined by a temperature < 38°C (100.4°F) sustained for at least 24 consecutive hours, within 72 hours of meropenem or micafungin initiation
  • Absence of signs or symptoms of infection within 72 hours of meropenem or micafungin initiation including but not limited to hypotension, erythema at catheter sites or cellulitis, positive imaging concerning for infection (e.g., pneumonia, osteomyelitis, abscesses etc.), positive cultures or rapid diagnostic tests, positive biomarkers (e.g. galactomannan), dysuria, hypothermia (≤ 35°C or ≤ 95°F) etc.
  • No modification to antimicrobial regimen after initiation of meropenem or micafungin unless the antibiotic modification is considered de-escalation (e.g. discontinuation of vancomycin)
Hour 72

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects In-hospital mortality or discharge to hospice
Time Frame: From hospital admission to death/discharge to hospice, up to 4 days
Death during in-hospital admission or discharge from in-hospital admission to hospice care
From hospital admission to death/discharge to hospice, up to 4 days
Hospital length of stay (days)
Time Frame: From hospital admission to discharge, up to 4 days
Number of days admitted to hospital
From hospital admission to discharge, up to 4 days
Time to defervescence (hours)
Time Frame: through study completion, an average of 4 days
  • Time of defervescence defined as the beginning of the 24 consecutive hour afebrile period
  • Time to defervescence defined as the time in hours from the initial documented fever to the beginning of the 24 consecutive hour afebrile period
through study completion, an average of 4 days
Days of therapy of meropenem or micafungin
Time Frame: through study completion, an average of 4 days
1 antibiotic x the number of days administered, any calendar day in which at least one dose is given counts as a full day of therapy - Time in days from initiation to discontinuation of meropenem or micafungin
through study completion, an average of 4 days
Rate of Clostridioides difficile infection on meropenem or micafungin
Time Frame: through study completion, an average of 4 days
Percentage of patients who develop Clostridioides difficile infection while on meropenem or micafungin
through study completion, an average of 4 days
Collection of Causes of any proven breakthrough infection while on meropenem or micafungin
Time Frame: through study completion, an average of 4 days
Collection of origin of proven breakthrough infection
through study completion, an average of 4 days

Collaborators and Investigators

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

Sponsor

Wake Forest University Health Sciences

Investigators

  • Principal Investigator: John Williamson, PharmD, Wake Forest University Health Sciences

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

Helpful Links

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 (Estimated)

August 1, 2024

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

March 2, 2023

First Submitted That Met QC Criteria

March 13, 2023

First Posted (Actual)

March 27, 2023

Study Record Updates

Last Update Posted (Actual)

May 16, 2024

Last Update Submitted That Met QC Criteria

May 15, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00088805

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

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