Febrile NeutropeniaPhase 4ELSA-FNNCT04948463
Early Versus Late Stopping of Antibiotics in Children With Cancer and High-risk Febrile Neutropenia
A Phase 4 study testing Piperacillin and Tazobactam for Injection, Cefepime Injection and Ceftazidime Injection in people with Febrile Neutropenia, run by Murdoch Childrens Research Institute at 1 site in Australia.
Trial summary
This randomised controlled trial will determine the non-inferiority of stopping empiric antibiotics prior to absolute neutrophil count (ANC) recovery (Early Stopping) versus stopping antibiotics upon ANC recovery (Standard of Care/ Late Stopping) , in children with cancer and high-risk febrile neutropenia (FN). Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Febrile Neutropenia
- What is being tested?
- Piperacillin and Tazobactam for Injection, Cefepime Injection and Ceftazidime Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteAustralia
- Study dates
- 15 Nov 2021to 17 Dec 2025
- Phase
- Phase 4
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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of
- Acute myeloid leukemia (AML) or acute lymphoblastic leukaemia (ALL) in dose-intensive phases of induction/re-induction, intensification or consolidation or
- ALL or acute lymphoblastic lymphoma patients on a TOT17 protocol or
- Any disease within 100 days of allogeneic or autologous HSCT
- Neutropenia (<500 cells/mm3)
- Afebrile (temperature <38.0°C) period for at least 48 hours and no more than 96 hours after at least one temperature measured by axillary or tympanic thermometer (≥38.0°C)
- Commenced on empiric FN antibiotics (any of piperacillin-tazobactam, cefepime, ceftazidime or vancomycin and ciprofloxacin)
Who cannot join
- Prolonged febrile neutropenia (documented daily temperature ≥38.0°C for ≥5 days)
- Documented positive blood culture since onset of FN episode and prior to randomisation
- Documented other infection (microbiologically or clinically documented) requiring antibiotic treatment since onset of FN episode and prior to randomisation
- Admitted to the ICU at the time of randomisation
- Clinical instability (One or more conscious state, respiratory rate, blood pressure, heart rate or oxygen saturations in MET criteria OR two or more respiratory rate, blood pressure, heart rate or oxygen saturations simultaneously (+/- 4 hrs) in the clinical review criteria in 48 hours prior to randomisation)
- Within 28 days of last randomisation
Trial locations and contacts
1 site in 1 country.
About this study
This randomised controlled trial will determine the non-inferiority of stopping empiric antibiotics prior to absolute neutrophil count (ANC) recovery (Early Stopping) versus stopping antibiotics upon ANC recovery (Standard of Care/ Late Stopping) , in children with cancer and high-risk febrile neutropenia (FN).
Read the detailed description
Febrile neutropenia (FN) is a common complication of childhood cancer treatment and a leading cause of hospital admission and antibiotic exposure. Management typically involves broad-spectrum antibiotics until resolution of fever and absolute neutrophil count (ANC) recovery >500 cells/mm3. However, despite the frequency with which FN occurs, evidence to guide duration of antibiotics is limited to observational studies and small randomised controlled trials.Current international clinical guidelines provide conflicting recommendations on when to cease empiric antibiotics for FN. Early cessation of antibiotics in FN may translate to reduced antibiotic exposure and limit potential harms including drug side-effects, antimicrobial resistance, Clostridioides difficile infection and microbiome disruption. This randomised controlled trial will use a composite endpoint of fever recurrence, physiological instability, new bacteremia, intensive care admission and death to determine the non-inferiority of stopping antibiotics prior to ANC recovery compared with standard of care (SOC), in children with cancer and high-risk FN. Adopting a health informatics approach, patient identification, consent, randomisation and reporting of outcomes will be embedded within the electronic medical record (EMR). Children with high-risk FN who have been afebrile and clinically stable for at least 48 hours will be randomised to cease antibiotics or continue SOC. Data on primary outcomes, antibiotic duration, length of stay, C. difficile infection and antimicrobial resistance will be automatically collected by the EMR. This is the first study of its kind in children with high-risk FN and adopts a novel embedded trial design. Results will inform optimal antibiotic duration in FN, potentially reducing unnecessary antibiotic exposure.
- Conditions
- Febrile Neutropenia
- Being tested
- Piperacillin and Tazobactam for Injection, Cefepime Injection, Ceftazidime Injection, Vancomycin Injection, Amikacin Injection
- Keywords
- Febrile Neutropenia, Cancer, Haematopoietic Stem Cell Transplantation (HSCT)
- Medical subject headings
- Febrile Neutropenia, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperacillin and Tazobactam for InjectionDrug
Given if patient has no known allergies, until ANC recovery at 100mg/kg (max 4g) 6 hourly.
Cefepime InjectionDrug
Given if patient has non life-threatening hypersensitivity (preferred option), until ANC recovery at 50mg/kg (max 2g) 8 hourly.
Ceftazidime InjectionDrug
If non life-threatening hypersensitivity (second option), given until ANC recovery at 50mg/kg (max 2g) 8 hourly
Vancomycin InjectionDrug
If life-threatening hypersensitivity given with ciprofloxacin, given until ANC recovery at 15mg/kg (max 500mg) 6 hourly
Amikacin InjectionDrug
Given until ANC recovery at 18-22.5mg/kg (max 1.5g) daily in combination with other antibiotic/s.
CiprofloxacinDrug
If life-threatening hypersensitivity given with vancomycin, given until ANC recovery at 10 mg/kg (max 400 mg) 12 hourly
Piperacillin and Tazobactam for InjectionDrug
Given if patient has no known allergies at 100mg/kg (max 4g) 6 hourly, stopping 48 hours post-fever resolution.
Cefepime InjectionDrug
If non life-threatening hypersensitivity (preferred option) at 50mg/kg (max 2g) 8 hourly, stopping 48 hours post-fever resolution
Ceftazidime InjectionDrug
If non life-threatening hypersensitivity (second option) at 50mg/kg (max 2g) 8 hourly, stopping 48 hours post-fever resolution
Vancomycin InjectionDrug
If life-threatening hypersensitivity given with ciprofloxacin at 15mg/kg (max 500mg) 6 hourly, stopping 48 hours post-fever resolution
Amikacin InjectionDrug
At 18-22.5mg/kg (max 1.5g) daily in combination with other antibiotic/s, stopping 48 hours post-fever resolution
CiprofloxacinDrug
If life-threatening hypersensitivity given with vancomycin at 10 mg/kg (max 400 mg) 12 hourly, stopping 48 hours post-fever resolution
| Study group | Role | What they receive |
|---|---|---|
| Early Stopping | Experimental | Stopping empiric FN antibiotics after resolution of fever for 48 hours, irrespective of absolute neutrophil count (ANC) Receives: Drug: Piperacillin and Tazobactam for Injection; Drug: Cefepime Injection; Drug: Ceftazidime Injection; Drug: Vancomycin Injection; Drug: Amikacin Injection; Drug: Ciprofloxacin |
| Standard of care | Active comparator | Continuing empiric FN antibiotics until resolution of fever for 48 hours and recovery of ANC as defined by the treating clinician but usually to ≥200-500/mm3 Receives: Drug: Piperacillin and Tazobactam for Injection; Drug: Cefepime Injection; Drug: Ceftazidime Injection; Drug: Vancomycin Injection; Drug: Amikacin Injection; Drug: Ciprofloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unfavourable clinical course occurring during the same period of severe neutropenia
Incidence of unfavourable clinical course, defined as any of the following: recurrence of fever, clinical instability (see below definition), admission to the intensive care unit, new positive blood culture collected after randomisation, or death
Measured: During the same episode of neutropenia, up to 28 days post-enrolment.
Secondary outcomes (14)
Fever recurrence
Incidence of fever recurrence (temperature ≥38 degrees Celsius)
Measured: Up to 28 days post-enrolment
Clinical instability
Incidence of clinical instability defined as; one or more vital signs (conscious state, respiratory rate, blood pressure, heart rate, oxygen saturation) meeting mandatory emergency (MET) call criteria OR two or more vital signs simultaneously (within 4 hours of each other) meeting clinical review criteria.
Measured: Up to 28 days post-enrolment
Admission to intensive care unit (ICU)
Incidence of admission to intensive care unit (all cause)
Measured: Up to 28 days post-enrolment
New positive blood culture
Incidence of positive blood culture
Measured: Up to 28 days post-enrolment
28 day all-cause and infection-related mortality
Incidence of all-cause and infection-related mortality, as defined post-mortem
Measured: Up to 28 days post-enrolment
Duration of neutropenia
Mean days of neutropenia defined as ANC <500 cells/mm3
Measured: During the same episode of neutropenia or up to 28 days post-enrolment
Clinician confidence and acceptability
Measured by number of patients for which randomisation is overridden in the Early Stopping arm and the recorded reason
Measured: Up to 28 days post-enrolment
Total antibiotic duration
Mean number of days antibiotics are administered
Measured: Up to 28 days post-enrolment
Length of hospital stay
Mean number of days admitted to the study site hospital ward
Measured: Up to 28 days post-enrolment, or until discharge from hospital (whichever is the later)
Readmission to hospital
Incidence of unplanned admission to the study site hospital
Measured: Up to 28 days post-enrolment
Development of C. difficile infection
Incidence of C. difficile infection detected in unformed stool
Measured: Up to 28 days post-enrolment
Development of an antibiotic resistant infection or colonisation
Incidence of antibiotic resistant infection or colonisation including Methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum beta-lactamases (ESBL)-producing enterobacterales, carbapenem-resistant enterobacteriaceae (CRE), Vancomycin-resistant Enterococcus (VRE)
Measured: Up to 28 days post-enrolment
Patient/parent/caregiver confidence
Number of patients that consent to study as proportion of patients eligible
Measured: Within 48 hours of having informed consent discussion with the study team
Patient/parent/caregiver acceptability
Number of patients for which randomisation is overridden in the Early Stopping arm due to withdrawn consent
Measured: Within 48-96 hours post assignment to intervention arm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2021
- Study start15 Nov 2021
- Primary completion17 Dec 2025
- Study completion17 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Febrile NeutropeniaStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Murdoch Childrens Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gabrielle Haeusler, Principal investigator, Murdoch Childrens Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04948463
- Sponsor's protocol ID
- 74690
- Acronym
- ELSA-FN
- Status last verified
- Nov 2025
- First submitted
- 18 Jun 2021
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Beginning 6 months following analysis and publication of the primary outcome, data will be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by the Murdoch Children's Research Institute's (MCRI's) independent data use review committee (not including trial sponsor-investigator) and who accept MCRI's conditions, under a collaborator agreement, for accessing all of the available participant data collected during the trial (after full deidentification).