Clinical trial NCT06278896: Early Neutropenic Fever De-escalation of Antibiotics Study
Official title: Early Neutropenic Fever De-escalation (END) of Antibiotics Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Hematologic Malignancy
Febrile Neutropenia
Antibiotic Stewardship
Keywords: Febrile Neutropenia
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2024-02-26
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Mortality, transfer to the ICU, septic shock, culture-confirmed bacteremia
timeFrame: 60 days
measure: Antibiotic utilization
timeFrame: 60 days
Secondary outcomes:
measure: Mortality post F&N
timeFrame: 60 days
measure: Drug resistance
timeFrame: 60 days
measure: Clostridium difficile infection
timeFrame: 60 days
measure: Candidiasis
timeFrame: 60 days
measure: Adverse Events
timeFrame: 60 days
measure: Allergic Reactions
timeFrame: 60 days
measure: Bacteremia
timeFrame: 60 days
measure: Neutropenia
timeFrame: 60 days
measure: Length of stay
timeFrame: 60 days
measure: Readmissions
timeFrame: 60 days
measure: Fever
timeFrame: 60 days
Other outcomes:
Locations:
Study officials:
affiliation: Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard
name: Lindsey R Baden, MD
role: PRINCIPAL_INVESTIGATOR
References: