Back to resultsAntimicrobial Revision in Persistent Febrile Neutropenia
Primary Purpose
Febrile Neutropenia
Status
Not yet recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Meropenem
Micafungin
Sponsored by
About this trial
This is an interventional treatment trial for Febrile Neutropenia focused on measuring acute myeloid leukemia, acute lymphocytic leukemia
Eligibility Criteria
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
Sites / Locations
- Wake Forest University Health Sciences
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Meropenem Arm
Micafungin Arm
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Global Success Rate
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)
Secondary Outcome Measures
Number of Subjects In-hospital mortality or discharge to hospice
Death during in-hospital admission or discharge from in-hospital admission to hospice care
Hospital length of stay (days)
Number of days admitted to hospital
Time to defervescence (hours)
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
Days of therapy of meropenem or micafungin
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
Rate of Clostridioides difficile infection on meropenem or micafungin
Percentage of patients who develop Clostridioides difficile infection while on meropenem or micafungin
Collection of Causes of any proven breakthrough infection while on meropenem or micafungin
Collection of origin of proven breakthrough infection
Full Information
NCT ID
NCT05784844
First Posted
March 2, 2023
Last Updated
September 28, 2023
Sponsor
Wake Forest University Health Sciences
1. Study Identification
Unique Protocol Identification Number
NCT05784844
Brief Title
Antimicrobial Revision in Persistent Febrile Neutropenia
Official Title
Antimicrobial Revision in Patients With Persistent Febrile Neutropenia: A Prospective, Randomized Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Febrile Neutropenia
Keywords
acute myeloid leukemia, acute lymphocytic leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Prospective, randomized, open-label, single center trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Meropenem Arm
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Micafungin Arm
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Meropenem
Other Intervention Name(s)
Merrem
Intervention Description
Carbapenem antibiotic
Intervention Type
Drug
Intervention Name(s)
Micafungin
Other Intervention Name(s)
Mycamine
Intervention Description
Echinocandin antifungal
Primary Outcome Measure Information:
Title
Global Success Rate
Description
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)
Time Frame
Hour 72
Secondary Outcome Measure Information:
Title
Number of Subjects In-hospital mortality or discharge to hospice
Description
Death during in-hospital admission or discharge from in-hospital admission to hospice care
Time Frame
From hospital admission to death/discharge to hospice, up to 4 days
Title
Hospital length of stay (days)
Description
Number of days admitted to hospital
Time Frame
From hospital admission to discharge, up to 4 days
Title
Time to defervescence (hours)
Description
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
Time Frame
through study completion, an average of 4 days
Title
Days of therapy of meropenem or micafungin
Description
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
Time Frame
through study completion, an average of 4 days
Title
Rate of Clostridioides difficile infection on meropenem or micafungin
Description
Percentage of patients who develop Clostridioides difficile infection while on meropenem or micafungin
Time Frame
through study completion, an average of 4 days
Title
Collection of Causes of any proven breakthrough infection while on meropenem or micafungin
Description
Collection of origin of proven breakthrough infection
Time Frame
through study completion, an average of 4 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Williamson, PharmD
Phone
336-713-3431
Email
johnwill@wakehealth.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Olivia Randazza, PharmD
Phone
336-702-4229
Email
orandazz@wakehealth.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Williamson, PharmD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivia Randazza, PharmD
Phone
336-702-4229
Email
orandazz@wakehealth.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
Citation
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Prevention and Treatment of Cancer-Related Infections Version 1.2022. Accessed July 12, 2022. https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1457
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Links:
URL
https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1457
Description
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
Learn more about this trial
Antimicrobial Revision in Persistent Febrile Neutropenia
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