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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04948463




Registration number
NCT04948463
Ethics application status
Date submitted
18/06/2021
Date registered
2/07/2021

Titles & IDs
Public title
Early Versus Late Stopping of Antibiotics in Children With Cancer and High-risk Febrile Neutropenia
Scientific title
Early Versus Late Stopping of Antibiotics in Children With Cancer and High-risk Febrile Neutropenia
Secondary ID [1] 0 0
74690
Universal Trial Number (UTN)
Trial acronym
ELSA-FN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Febrile Neutropenia 0 0
Condition category
Condition code
Blood 0 0 0 0
Other blood disorders
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Unfavourable clinical course occurring during the same period of severe neutropenia
Timepoint [1] 0 0
During the same episode of neutropenia, up to 28 days post-enrolment.
Secondary outcome [1] 0 0
Fever recurrence
Timepoint [1] 0 0
Up to 28 days post-enrolment
Secondary outcome [2] 0 0
Clinical instability
Timepoint [2] 0 0
Up to 28 days post-enrolment
Secondary outcome [3] 0 0
Admission to intensive care unit (ICU)
Timepoint [3] 0 0
Up to 28 days post-enrolment
Secondary outcome [4] 0 0
New positive blood culture
Timepoint [4] 0 0
Up to 28 days post-enrolment
Secondary outcome [5] 0 0
28 day all-cause and infection-related mortality
Timepoint [5] 0 0
Up to 28 days post-enrolment
Secondary outcome [6] 0 0
Duration of neutropenia
Timepoint [6] 0 0
During the same episode of neutropenia or up to 28 days post-enrolment
Secondary outcome [7] 0 0
Clinician confidence and acceptability
Timepoint [7] 0 0
Up to 28 days post-enrolment
Secondary outcome [8] 0 0
Total antibiotic duration
Timepoint [8] 0 0
Up to 28 days post-enrolment
Secondary outcome [9] 0 0
Length of hospital stay
Timepoint [9] 0 0
Up to 28 days post-enrolment, or until discharge from hospital (whichever is the later)
Secondary outcome [10] 0 0
Readmission to hospital
Timepoint [10] 0 0
Up to 28 days post-enrolment
Secondary outcome [11] 0 0
Development of C. difficile infection
Timepoint [11] 0 0
Up to 28 days post-enrolment
Secondary outcome [12] 0 0
Development of an antibiotic resistant infection or colonisation
Timepoint [12] 0 0
Up to 28 days post-enrolment
Secondary outcome [13] 0 0
Patient/parent/caregiver confidence
Timepoint [13] 0 0
Within 48 hours of having informed consent discussion with the study team
Secondary outcome [14] 0 0
Patient/parent/caregiver acceptability
Timepoint [14] 0 0
Within 48-96 hours post assignment to intervention arm

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)
Minimum age
No limit
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2026
Actual
Sample size
Target
312
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Children's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3052 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gabrielle Haeusler
Address 0 0
Murdoch Childrens Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Alannah Rudkin
Address 0 0
Country 0 0
Phone 0 0
03 8341 6200
Fax 0 0
Email 0 0
alannah.rudkin@mcri.edu.au
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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).

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Analytic code
When will data be available (start and end dates)?
6 months following analysis and publication of the primary outcome
Available to whom?
Requests for access to previously published anonymised datasets by the scientific community will be reviewed and determined by an independent committee within the MCRI and in accordance with institute policy.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04948463