Febrile Neutropenia
Conditions
Keywords
acute myeloid leukemia, acute lymphocytic leukemia
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.
Interventions
DRUGMeropenem
Carbapenem antibiotic
DRUGMicafungin
Echinocandin antifungal
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, randomized, open-label, single center trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Days 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 |
| 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 |
| 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 period |
Outcome results
None listed