Early Neutropenic Fever De-escalation of Antibiotics Study

Phase 3Not Yet RecruitingNCT06278896

Brigham and Women's Hospital260 enrolled

Overview

This is a randomized, open label clinical trial among individuals with hematologic conditions. The trial aims to evaluate the safety and clinical outcomes of de-escalating antibiotic therapy among stable individuals diagnosed with neutropenic fever, in which no bacterial infection has been identified.

Background: The Infectious Disease Society of America (IDSA) guidelines for febrile neutropenia conflict with several other international guidelines on duration of antibiotic therapy in patients with febrile neutropenia without a documented infectious source. The IDSA recommends continuing antibiotic therapy until clear signs of marrow recovery, while other guidelines, including the European guidelines, allow for earlier discontinuation if no source of bacterial infection is identified. Benefits of earlier discontinuation of antibiotics include mitigating the risk of induction and amplification of antibiotic resistance, decreased disruption of the microbiome, as well as minimizing potential side effects and complications associated with long-term antibiotic use. To date the only randomized clinical trial in adults evaluating an abridged course of antibiotic therapy in high-risk patients with febrile neutropenia (defined as neutropenia for at least 7 days) was a superiority study that demonstrated fewer days of antibiotic use in the control arm. Safety data were a secondary outcome. Further research is needed to assess the safety and clinical outcomes of targeted antibiotic therapy for patients with febrile neutropenia. Study Design: This is a randomized, open label clinical trial among individuals with hematologic conditions. The trial aims to evaluate the safety and clinical outcomes of de-escalating antibiotic therapy among stable individuals diagnosed with neutropenic fever, in which no bacterial infection has been identified. Treatment Regimen: Intervention Arm (Arm A): Stop antibiotic therapy after episode of fever if afebrile for 48 hours, no clinically documented source of bacterial infection, and no hemodynamic or respiratory decompensation. Control Arm (Arm B): Continue antibiotic therapy per IDSA guidelines until count recovery and/or standard of care as deemed by inpatient providers. Study Participants: The study population will comprise adults who have hematologic high-risk neutropenia (likely \> 7 days).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

260

Conditions

Hematologic Malignancy Febrile Neutropenia Antibiotic Stewardship

Interventions

Cessation of antibioticsDRUG

Stop antibiotic therapy after episode of fever if afebrile for 48 hours, no clinically documented source of bacterial infection, and no hemodynamic or respiratory decompensation.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Participant or healthcare proxy with the ability to understand and willingness to sign an informed consent. 2. Adults \>18 years old. 3. Likely to have neutropenia \> 7 days including such conditions as: acute leukemia; lymphoproliferative disease; multiple myeloma; myelodysplastic syndrome; bone marrow aplasia and autologous or allogeneic hematopoietic stem cell transplantation. Neutropenia defined as absolute neutrophil count \<500. 4. Received or planned to receive cytotoxic chemotherapy. No restrictions on prior therapy regarding dose or agent. 5. High-risk neutropenia defined as expected duration of absolute neutrophil count less than 500 cells/µL for seven or more days. 6. Admitted as an inpatient at Mass General Brigham or Dana Farber Cancer Institute (DFCI). 7. Initial fever (defined as a single oral temperature of ≥38.3°C or a temperature of ≥38.0°C sustained over a one-hour period) during hospital admission or as reason for admission. 8. Has been afebrile for 48 hours. Exclusion Criteria: 1. Microbiologically or clinically suspected bacterial infection after index fever. 2. Exposure to treatment antibacterial therapy 72 hours before first fever occurrence other than antibiotics deemed as prophylaxis.

Outcomes

Primary Outcomes

Mortality, transfer to the ICU, septic shock, culture-confirmed bacteremia

To compare number of patients with a 60-day composite of mortality, transfer to the ICU, septic shock, culture-confirmed bacteremia in each arm.

Time frame: 60 days

Antibiotic utilization

To compare the days of antibiotic spectrum coverage (DASC), in each arm between randomization and count recovery.

Time frame: 60 days

Secondary Outcomes

Mortality post F&N

To compare the rates of mortality within 60 days after first neutropenic fever in each arm.

Time frame: 60 days

Drug resistance

To compare the rates of acquisition of multidrug resistant gram-negative bacilli (resistant to 3 or more antibiotic classes) and vancomycin resistant enterococci within 60 days after first neutropenic fever in each arm.

Time frame: 60 days

Clostridium difficile infection

To compare the rates of Clostridium difficile infection (CDI) within 60 days after first neutropenic fever infection in each arm.

Time frame: 60 days

Candidiasis

To compare the rates of candidemia and invasive candidiasis within 60 days after first neutropenic fever in each arm.

Time frame: 60 days

Adverse Events

To compare the rates of grade 3, 4, and 5 adverse events in each arm within 60 days after first neutropenic fever.

Time frame: 60 days

Central Contacts

Lindsey R Baden, MD

CONTACT

617-525-8418 lbaden@bwh.harvard.edu

Alisse D Hannaford, MD

CONTACT

617-525-8418 ahannaford@mgh.harvard.edu

Data from ClinicalTrials.gov

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