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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT07051525
Registration number
NCT07051525
Ethics application status
Date submitted
21/04/2025
Date registered
4/07/2025
Date last updated
4/07/2025
Titles & IDs
Public title
Early Versus Late Stopping of Antibiotics in Adults With High-risk Hematological Malignancies/Receiving Cellular Therapies and Fever
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Scientific title
Early Versus Late Stopping of Antibiotics in Adults With High Risk Haematological Malignancies/Receiving Cellular Therapies and Fever (ELSA- Adult)
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Secondary ID [1]
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2024.406
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Secondary ID [2]
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24/236
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Universal Trial Number (UTN)
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Trial acronym
ELSA-Adult
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Leukemia
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CART Therapy
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Transplantation, Stem Cell
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Infections, Bacterial
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Early antibiotic cessation alert
Experimental: STOP - early discontinuation of empiric antibiotic therapy - Short course antibiotics (STOP): Antibiotics will be commenced at onset of fever and stopped once afebrile for 48-96 hours and clinically stable.
No intervention: SOC - standard of care continuation of empiric antibiotic therapy - Standard of care (SOC): Antibiotics will be commenced at onset of fever and continued for a duration as per clinician's discretion, typically until resolution of fever, clinical recovery and ANC =200- 500 cells/mm3.
Treatment: Drugs: Early antibiotic cessation alert
For all patients, antibiotics will be commenced at onset of fever. For those in the intervention arm an alert will fire in the electronic medical record once a patient is afebrile for 48-96 hours and clinically stable.
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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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Days free of antibiotic therapy in 28 days post randomization (termed empiric antibiotic free days (EAFDs))
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Assessment method [1]
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The primary study outcome is duration of days free of antibiotics within 28 days of study allocation. Measured as antibiotic free days in last 28 days post fever onset
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Timepoint [1]
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28 days after randomization
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Secondary outcome [1]
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Days alive and free of antibiotic therapy in 28 days post randomization
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Assessment method [1]
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Days alive and free of antibiotic therapy in 28 days post randomization
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Timepoint [1]
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28 days after randomization
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Secondary outcome [2]
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Recurrence of fever (>38deg Celsius) beyond randomization
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Assessment method [2]
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Recurrence of fever (\>38deg Celsius, confirmed on second reading within 1 hour) post randomization during the same episode of neutropenia, not associated with blood product transfusion * In CAR T treated patients, grade of cytokine release syndrome (CRS), immune-cell associated neurotoxicity (ICANS) at time of fever and any recurrent fever.
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Timepoint [2]
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same episode of neutropenia - until ANC>500 cells/mm3
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Secondary outcome [3]
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Number of occasions antibiotic therapy is recommenced with treatment intent
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Assessment method [3]
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Number of events antibiotic therapy is recommenced with treatment intent (excluding prophylaxis)
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Timepoint [3]
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Within 28 days after randomization
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Secondary outcome [4]
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Days of antibiotic therapy during neutropenic period
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Assessment method [4]
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Days of antibiotic therapy during neutropenic period until ANC\>500 cells/mm3
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Timepoint [4]
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Neutropenic period - until ANC>500 cells/mm3
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Secondary outcome [5]
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Number of intensive care unit (ICU) admissions
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Assessment method [5]
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Admission to intensive care for organ support during the same pre-neutropenic and neutropenic period post randomization
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Timepoint [5]
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pre-neutropenic and neutropenic period post randomization (until ANC>500 cells/mm3)
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Secondary outcome [6]
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Number of events of clinical instability
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Assessment method [6]
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Number of events of clinical instability (defined by blood pressure, oxygen saturations, respiratory rate and heart rate meeting at least 1 Medical Emergency Team (MET) call criteria or 2 clinical review criteria)
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Timepoint [6]
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28 days after randomization
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Secondary outcome [7]
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Number of events of new positive blood culture
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Assessment method [7]
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Number of events of new positive blood culture post randomization (defined by CDC criteria)
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Timepoint [7]
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28 days after randomization
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Secondary outcome [8]
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28 day all-cause mortality and infection-related mortality
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Assessment method [8]
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28 day all-cause mortality and infection-related mortality (as assessed by an independent data safety monitoring board)
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Timepoint [8]
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28 days after randomization
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Secondary outcome [9]
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Measure number of patient days of total hospital admission
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Assessment method [9]
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Duration of in-hospital length of stay calculated from randomization date and time to discharge from hospital ward or Hospital-In-The-Home (HITH)
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Timepoint [9]
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Measure number of days of total hospital length of stay during enrolment (admission until discharge from hospital inpatient and HITH)
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Secondary outcome [10]
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Total number of days of in-hospital length of stay
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Assessment method [10]
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Duration of in-hospital length of stay calculated from randomization date and time to discharge/transfer from in- hospital ward
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Timepoint [10]
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Total number of days of in-hospital length of stay
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Secondary outcome [11]
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Total hospital length of stay post randomisation
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Assessment method [11]
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Duration of in-hospital length of stay calculated from randomization date and time to discharge from hospital ward or HITH
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Timepoint [11]
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Total hospital length of stay post randomization to discharge (from ward or HITH)
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Secondary outcome [12]
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Number of unplanned hospital readmissions
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Assessment method [12]
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Unplanned readmission to hospital within 60 days of randomization, defined as any admission that is not due to planned chemotherapy, conditioning or routine neutropenic monitoring as per standard protocols.
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Timepoint [12]
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within 60 days of randomization
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Secondary outcome [13]
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Number of positive C.difficile infections
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Assessment method [13]
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Number of development of C.difficile infection (defined by diarrhea, positive toxin polymerase chain reaction (PCR) and lack of other cause) within 6 months of randomization
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Timepoint [13]
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within 6 months of randomization
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Secondary outcome [14]
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Number of antibiotic resistant infection or colonizations
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Assessment method [14]
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New antibiotic resistant (Methicillin-resistant Staphylococcus aureus (MRSA), Extended-Spectrum Beta-Lactamases (ESBL) producing Enterobacterales, Carbapenem-resistant Enterobacterales (CRE), Vancomycin-resistant Enterococcus (VRE) infection or colonization detected within 180 days post randomization
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Timepoint [14]
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within 180 days post randomization
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Secondary outcome [15]
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Number of Clinically defined infections during pre-neutropenic and neutropenic period
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Assessment method [15]
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Number of Clinically defined infections during pre-neutropenic and neutropenic period
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Timepoint [15]
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pre-neutropenic and neutropenic period until ANC>500 cells/mm3
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Secondary outcome [16]
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Number of clinically defined infections post randomization
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Assessment method [16]
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Number of clinically defined infections post randomization
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Timepoint [16]
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post randomization until 28days
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Secondary outcome [17]
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Number of microbiologically defined infections during pre-neutropenic and neutropenic period
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Assessment method [17]
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Number of microbiologically defined infections during pre-neutropenic and neutropenic period
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Timepoint [17]
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during pre-neutropenic and neutropenic period until ANC>500 cells/mm3
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Secondary outcome [18]
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Number of microbiologically defined infections post randomization
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Assessment method [18]
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Number of microbiologically defined infections post randomisation
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Timepoint [18]
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post randomization until 28days
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Eligibility
Key inclusion criteria
Adult patients ( =18 years) who are receiving either:
* Conditioning chemotherapy for an autologous or allogeneic haematopoietic cell transplant or CAR T cell therapy, OR
* Induction remission chemotherapy for acute leukaemia,
AND develop fever ( =38degC) between time of initiation of chemotherapy/conditioning administration and ANC recovery to =500 cells/mm3 post the ANC nadir,
AND fever subsequently has settled (<38degC) for =48 and <96h hours.
[participants will be stratified into pre-neutropenic (ANC =500 cells/mm3) and neutropenic (ANC<500 cells/mm3) strata based on ANC level at 48 hours post fever onset, as per international consensus definition of neutropenic fever]
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Minimum age
18
Years
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Maximum age
No limit
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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
* - Prolonged fever prior to defervescence (documented daily temperature =38.0°C for = 5 days)
* Documented positive blood culture for bacteria since onset of fever episode and prior to randomisation
* Documented other infection (clinically or microbiologically defined) requiring antibacterial treatment
* Grade 2 or higher mucositis (WHO) or neutropenic enterocolitis
* Clinically unstable and/or admission to ICU at time of potential randomization
* Within 28 days of last randomization
* Prior randomization during current chemotherapy/conditioning cycle
* Pregnant or breastfeeding
* Currently being treated for CRS Grade 3 or 4, and/or ICANS Grade 3 or 4 (defined as per ASTCT Consensus Guidelines, Lee et al)
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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
Not applicable
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Not yet 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
5/07/2025
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Actual
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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
5/09/2027
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Actual
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Sample size
Target
214
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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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Peter MacCallum Cancer Centre - Melbourne
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Recruitment hospital [2]
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Royal Melbourne Hospital - Melbourne
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Recruitment postcode(s) [1]
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3000 - Melbourne
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Recruitment postcode(s) [2]
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3050 - Melbourne
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Funding & Sponsors
Primary sponsor type
Other
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Name
Peter MacCallum Cancer Centre, Australia
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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Melbourne Health
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
Pre-neutropenic fever (PNF) (fever following chemotherapy but before developing low white cells) and neutropenic fever (NF) (fever in the setting of low white cells) are very common after chemotherapy for acute leukemia, bone marrow transplantation or Chimeric Antigen Receptor T-cell (CAR T) therapy. Often, there is no bacterial cause for fever found, and in the setting of a well patient with resolved fever, some studies have shown it to be safe to cease antibiotic therapy which was commenced at the onset of fever. This reduces the overall exposure to antibiotics, which can be beneficial to the patient (reduced risk of resistant bugs emerging, reduced serious side effects). However, some subgroups of high-risk patients have been underrepresented in these studies (in particular, those who have received a bone marrow transplant from a donor, those with longer duration of low white cells) and none have been performed in Australia, hence applying this data to our setting and patient groups is indirect and further data are needed. This study plans to recruit participants who have received chemotherapy for acute leukemia or a stem cell transplant (either their own cells or a donor's cells) or CAR T-cell therapy and perform a trial to compare early stopping of antibiotics (STOP arm) to the standard of care, which traditionally involves continuing antibiotics until the white cell count reaches above a specific threshold. The primary study outcome is duration of days free of antibiotics within 28 days of study allocation. The investigators will also observe for important clinical outcomes including rates of fever recurrence, bloodstream and other infections, intensive care admission and mortality. Patients will stay in hospital during this period, even in the setting of stopping antibiotics, and these antibiotics can be recommenced urgently according to the sepsis protocol if there is concern for infection.
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Trial website
https://clinicaltrials.gov/study/NCT07051525
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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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Abby P Douglas, MBBS PhD FRACP
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Address
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Peter MacCallum Cancer Centre; National Centre for Infections in Cancer
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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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Principal Investigator
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Address
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Country
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Phone
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+61448503643
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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
Data sharing statement
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/NCT07051525
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