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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04948463
Registration number
NCT04948463
Ethics application status
Date submitted
18/06/2021
Date registered
2/07/2021
Date last updated
15/03/2024
Titles & IDs
Public title
Early Versus Late Stopping of Antibiotics in Children With Cancer and High-risk Febrile Neutropenia
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Scientific title
Early Versus Late Stopping of Antibiotics in Children With Cancer and High-risk Febrile Neutropenia
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Secondary ID [1]
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74690
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Universal Trial Number (UTN)
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Trial acronym
ELSA-FN
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Febrile Neutropenia
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Condition category
Condition code
Blood
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Other blood disorders
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Injuries and Accidents
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Other injuries and accidents
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Piperacillin and Tazobactam for Injection
Treatment: Drugs - Cefepime Injection
Treatment: Drugs - Ceftazidime Injection
Treatment: Drugs - Vancomycin Injection
Treatment: Drugs - Amikacin Injection
Treatment: Drugs - Ciprofloxacin
Treatment: Drugs - Piperacillin and Tazobactam for Injection
Treatment: Drugs - Cefepime Injection
Treatment: Drugs - Ceftazidime Injection
Treatment: Drugs - Vancomycin Injection
Treatment: Drugs - Amikacin Injection
Treatment: Drugs - Ciprofloxacin
Experimental: Early Stopping - Stopping empiric FN antibiotics after resolution of fever for 48 hours, irrespective of absolute neutrophil count (ANC)
Active Comparator: Standard of care - 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
Treatment: Drugs: Piperacillin and Tazobactam for Injection
Given if patient has no known allergies, until ANC recovery at 100mg/kg (max 4g) 6 hourly.
Treatment: Drugs: Cefepime Injection
Given if patient has non life-threatening hypersensitivity (preferred option), until ANC recovery at 50mg/kg (max 2g) 8 hourly.
Treatment: Drugs: Ceftazidime Injection
If non life-threatening hypersensitivity (second option), given until ANC recovery at 50mg/kg (max 2g) 8 hourly
Treatment: Drugs: Vancomycin Injection
If life-threatening hypersensitivity given with ciprofloxacin, given until ANC recovery at 15mg/kg (max 500mg) 6 hourly
Treatment: Drugs: Amikacin Injection
Given until ANC recovery at 18-22.5mg/kg (max 1.5g) daily in combination with other antibiotic/s.
Treatment: Drugs: Ciprofloxacin
If life-threatening hypersensitivity given with vancomycin, given until ANC recovery at 10 mg/kg (max 400 mg) 12 hourly
Treatment: Drugs: Piperacillin and Tazobactam for Injection
Given if patient has no known allergies at 100mg/kg (max 4g) 6 hourly, stopping 48 hours post-fever resolution.
Treatment: Drugs: Cefepime Injection
If non life-threatening hypersensitivity (preferred option) at 50mg/kg (max 2g) 8 hourly, stopping 48 hours post-fever resolution
Treatment: Drugs: Ceftazidime Injection
If non life-threatening hypersensitivity (second option) at 50mg/kg (max 2g) 8 hourly, stopping 48 hours post-fever resolution
Treatment: Drugs: Vancomycin Injection
If life-threatening hypersensitivity given with ciprofloxacin at 15mg/kg (max 500mg) 6 hourly, stopping 48 hours post-fever resolution
Treatment: Drugs: Amikacin Injection
At 18-22.5mg/kg (max 1.5g) daily in combination with other antibiotic/s, stopping 48 hours post-fever resolution
Treatment: Drugs: Ciprofloxacin
If life-threatening hypersensitivity given with vancomycin at 10 mg/kg (max 400 mg) 12 hourly, stopping 48 hours post-fever resolution
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Unfavourable clinical course occurring during the same period of severe neutropenia
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Assessment method [1]
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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
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Timepoint [1]
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During the same episode of neutropenia, up to 28 days post-enrolment.
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Secondary outcome [1]
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Fever recurrence
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Assessment method [1]
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Incidence of fever recurrence (temperature =38 degrees Celsius)
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Timepoint [1]
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Up to 28 days post-enrolment
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Secondary outcome [2]
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Clinical instability
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Assessment method [2]
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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.
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Timepoint [2]
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Up to 28 days post-enrolment
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Secondary outcome [3]
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Admission to intensive care unit (ICU)
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Assessment method [3]
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Incidence of admission to intensive care unit (all cause)
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Timepoint [3]
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Up to 28 days post-enrolment
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Secondary outcome [4]
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New positive blood culture
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Assessment method [4]
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Incidence of positive blood culture
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Timepoint [4]
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Up to 28 days post-enrolment
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Secondary outcome [5]
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28 day all-cause and infection-related mortality
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Assessment method [5]
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Incidence of all-cause and infection-related mortality, as defined post-mortem
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Timepoint [5]
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Up to 28 days post-enrolment
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Secondary outcome [6]
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Duration of neutropenia
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Assessment method [6]
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Mean days of neutropenia defined as ANC <500 cells/mm3
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Timepoint [6]
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During the same episode of neutropenia or up to 28 days post-enrolment
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Secondary outcome [7]
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Clinician confidence and acceptability
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Assessment method [7]
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Measured by number of patients for which randomisation is overridden in the Early Stopping arm and the recorded reason
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Timepoint [7]
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Up to 28 days post-enrolment
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Secondary outcome [8]
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Total antibiotic duration
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Assessment method [8]
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Mean number of days antibiotics are administered
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Timepoint [8]
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Up to 28 days post-enrolment
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Secondary outcome [9]
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Length of hospital stay
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Assessment method [9]
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Mean number of days admitted to the study site hospital ward
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Timepoint [9]
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Up to 28 days post-enrolment, or until discharge from hospital (whichever is the later)
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Secondary outcome [10]
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Readmission to hospital
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Assessment method [10]
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Incidence of unplanned admission to the study site hospital
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Timepoint [10]
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Up to 28 days post-enrolment
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Secondary outcome [11]
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Development of C. difficile infection
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Assessment method [11]
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Incidence of C. difficile infection detected in unformed stool
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Timepoint [11]
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Up to 28 days post-enrolment
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Secondary outcome [12]
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Development of an antibiotic resistant infection or colonisation
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Assessment method [12]
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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)
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Timepoint [12]
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Up to 28 days post-enrolment
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Secondary outcome [13]
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Patient/parent/caregiver confidence
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Assessment method [13]
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Number of patients that consent to study as proportion of patients eligible
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Timepoint [13]
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Within 48 hours of having informed consent discussion with the study team
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Secondary outcome [14]
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Patient/parent/caregiver acceptability
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Assessment method [14]
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Number of patients for which randomisation is overridden in the Early Stopping arm due to withdrawn consent
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Timepoint [14]
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Within 48-96 hours post assignment to intervention arm
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Eligibility
Key inclusion criteria
1. 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
2. Neutropenia (<500 cells/mm3)
3. 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)
4. Commenced on empiric FN antibiotics (any of piperacillin-tazobactam, cefepime,
ceftazidime or vancomycin and ciprofloxacin)
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Minimum age
No limit
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Maximum age
18
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Prolonged febrile neutropenia (documented daily temperature =38.0°C for =5 days)
2. Documented positive blood culture since onset of FN episode and prior to randomisation
3. Documented other infection (microbiologically or clinically documented) requiring
antibiotic treatment since onset of FN episode and prior to randomisation
4. Admitted to the ICU at the time of randomisation
5. 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)
6. Within 28 days of last randomisation
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
15/11/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/08/2026
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Actual
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Sample size
Target
312
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Royal Children's Hospital - Melbourne
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Recruitment postcode(s) [1]
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3052 - Melbourne
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Funding & Sponsors
Primary sponsor type
Other
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Name
Murdoch Childrens Research Institute
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief 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).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04948463
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Gabrielle Haeusler
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Address
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Murdoch Childrens Research Institute
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Alannah Rudkin
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Address
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Country
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Phone
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03 8341 6200
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04948463
Download to PDF