Hematologic MalignancyPhase 3ENDNCT06278896
Early Neutropenic Fever De-escalation of Antibiotics Study
A Phase 3 study testing Cessation of antibiotics in people with Hematologic Malignancy and Febrile Neutropenia, run by Brigham and Women's Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancy, Febrile Neutropenia, Antibiotic Stewardship
- What is being tested?
- Cessation of antibiotics
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 260 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2024to 1 Mar 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant or healthcare proxy with the ability to understand and willingness to sign an informed consent.
- Adults >18 years old.
- 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.
- Received or planned to receive cytotoxic chemotherapy. No restrictions on prior therapy regarding dose or agent.
- High-risk neutropenia defined as expected duration of absolute neutrophil count less than 500 cells/µL for seven or more days.
- Admitted as an inpatient at Mass General Brigham or Dana Farber Cancer Institute (DFCI).
- 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.
- Has been afebrile for 48 hours.
Who cannot join
- Microbiologically or clinically suspected bacterial infection after index fever.
- Exposure to treatment antibacterial therapy 72 hours before first fever occurrence other than antibiotics deemed as prophylaxis.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Early Neutropenic Fever De-escalation (END) of Antibiotics Study
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.
Read the 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).
- Being tested
- Cessation of antibiotics
- Keywords
- Febrile Neutropenia
- Medical subject headings
- Hematologic Neoplasms, Febrile Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cessation of antibioticsDrug
Also called Stop 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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention Arm | Experimental | 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. Receives: Drug: Cessation of antibiotics |
| Control Arm | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 60 days
Antibiotic utilization
To compare the days of antibiotic spectrum coverage (DASC), in each arm between randomization and count recovery.
Measured: 60 days
Secondary outcomes (11)
Mortality post F&N
To compare the rates of mortality within 60 days after first neutropenic fever in each arm.
Measured: 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.
Measured: 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.
Measured: 60 days
Candidiasis
To compare the rates of candidemia and invasive candidiasis within 60 days after first neutropenic fever in each arm.
Measured: 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.
Measured: 60 days
Allergic Reactions
To compare the rates of allergic reactions or side effects attributed to antibiotics that required antibiotic cessation or change within 60 days after first neutropenic fever.
Measured: 60 days
Bacteremia
To compare the rates of bacteremia within 60 days after randomization.
Measured: 60 days
Neutropenia
To compare the rates of neutropenia at antibiotic stop date.
Measured: 60 days
Length of stay
To compare the length of hospital stay in each arm.
Measured: 60 days
Readmissions
To compare the rates of non-elective hospital readmission within 60 days in each arm.
Measured: 60 days
Fever
To compare the rates of new fever after index fever in each arm.
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2024
- Study start1 Mar 2024 (estimated)
- Primary completion1 Mar 2026 (estimated)
- Study completion1 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignancyStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute
- Responsible party
- Principal investigator, Lindsey R. Baden, MD, Brigham and Women's Hospital
- Investigators
- Lindsey R Baden, MD, Principal investigator, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06278896
- Sponsor's protocol ID
- 23-684-END
- Acronym
- END
- Status last verified
- Feb 2024
- First submitted
- 3 Jan 2024
- Last updated
- 26 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No