Early Neutropenic Fever De-escalation of Antibiotics Study

NCT ID: NCT06278896

Last Updated: 2024-02-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-01
• Study Completion Date: 2028-03-01

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).

Conditions

Hematologic Malignancy; Febrile Neutropenia; Antibiotic Stewardship

Study Design

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

Study Groups

Intervention Arm

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

Group Type: EXPERIMENTAL

Cessation of antibiotics

Intervention Type: DRUG

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

Participants will continue antibiotic therapy until count recovery and/or standard of care as deemed by inpatient providers, which is the current guidelines recommended by the IDSA.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Cessation of antibiotics

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.

Intervention Type: DRUG

Other Intervention Names

Stop antibiotics

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.

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

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Lindsey R. Baden, MD

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lindsey R Baden, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard

Central Contacts

Lindsey R Baden, MD

Role: CONTACT

lbaden@bwh.harvard.edu

617-525-8418

Alisse D Hannaford, MD

Role: CONTACT

ahannaford@mgh.harvard.edu

617-525-8418

Other Identifiers

23-684-END

Identifier Type: -

Identifier Source: org_study_id