Antimicrobial Revision in Persistent Febrile Neutropenia
- Registration Number
- NCT05784844
- Lead Sponsor
- Wake Forest University Health Sciences
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- ≥ 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Micafungin Arm Micafungin 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. Meropenem Arm Meropenem 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.
- Primary Outcome Measures
Name Time Method Global Success Rate 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)
- Secondary Outcome Measures
Name Time Method Hospital length of stay (days) From hospital admission to discharge, up to 4 days Number of days admitted to hospital
Collection of Causes of any proven breakthrough infection while on meropenem or micafungin through study completion, an average of 4 days Collection of origin of proven breakthrough infection
Time to defervescence (hours) 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 periodDays of therapy of meropenem or micafungin 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
Number of Subjects In-hospital mortality or discharge to hospice 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
Rate of Clostridioides difficile infection on meropenem or micafungin through study completion, an average of 4 days Percentage of patients who develop Clostridioides difficile infection while on meropenem or micafungin
Trial Locations
- Locations (1)
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States