Antimicrobial Revision in Persistent Febrile Neutropenia

NCT ID: NCT05784844

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-31
• Study Completion Date: 2025-04-30

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.

Conditions

Febrile Neutropenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Meropenem

Intervention Type: DRUG

Carbapenem antibiotic

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.

Group Type: ACTIVE_COMPARATOR

Micafungin

Intervention Type: DRUG

Echinocandin antifungal

Interventions

Meropenem

Carbapenem antibiotic

Intervention Type: DRUG

Micafungin

Echinocandin antifungal

Intervention Type: DRUG

Other Intervention Names

Merrem; Mycamine

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Williamson, PharmD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

References

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

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

Related Links

https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1457

National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

Other Identifiers

IRB00088805

Identifier Type: -

Identifier Source: org_study_id