Early Versus Late Stopping of Antibiotics in Children With Cancer and High-risk Febrile Neutropenia

NCT04948463 | Completed Phase 4

• 1 other identifier: 74690
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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).

Conditions

Febrile Neutropenia

Keywords

Febrile Neutropenia; Cancer; Haematopoietic Stem Cell Transplantation (HSCT)

Outcome Measures

Primary Outcomes (1)

• 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

  During the same episode of neutropenia, up to 28 days post-enrolment.

Secondary Outcomes (14)

• Fever recurrence

  Up to 28 days post-enrolment

• Clinical instability

  Up to 28 days post-enrolment

• Admission to intensive care unit (ICU)

  Up to 28 days post-enrolment

• New positive blood culture

  Up to 28 days post-enrolment

• 28 day all-cause and infection-related mortality

  Up to 28 days post-enrolment

Study Arms (2)

Early Stopping

EXPERIMENTAL

Stopping empiric FN antibiotics after resolution of fever for 48 hours, irrespective of absolute neutrophil count (ANC)

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

Drug: Piperacillin and Tazobactam for Injection; Drug: Cefepime Injection; Drug: Ceftazidime Injection; Drug: Vancomycin Injection; Drug: Amikacin Injection; Drug: Ciprofloxacin

Interventions

Piperacillin and Tazobactam for Injection DRUG

Given if patient has no known allergies, until ANC recovery at 100mg/kg (max 4g) 6 hourly.

Standard of care

Cefepime Injection DRUG

Given if patient has non life-threatening hypersensitivity (preferred option), until ANC recovery at 50mg/kg (max 2g) 8 hourly.

Standard of care

Ceftazidime Injection DRUG

If non life-threatening hypersensitivity (second option), given until ANC recovery at 50mg/kg (max 2g) 8 hourly

Standard of care

Vancomycin Injection DRUG

If life-threatening hypersensitivity given with ciprofloxacin, given until ANC recovery at 15mg/kg (max 500mg) 6 hourly

Standard of care

Amikacin Injection DRUG

Given until ANC recovery at 18-22.5mg/kg (max 1.5g) daily in combination with other antibiotic/s.

Standard of care

Ciprofloxacin DRUG

If life-threatening hypersensitivity given with vancomycin, given until ANC recovery at 10 mg/kg (max 400 mg) 12 hourly

Standard of care

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead

Study Sites (1)

Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

Location

MeSH Terms

Conditions

Febrile Neutropenia; Neoplasms

Interventions

Piperacillin; Tazobactam; Injections; Cefepime; Ceftazidime; Vancomycin; Amikacin; Ciprofloxacin

Condition Hierarchy (Ancestors)

Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Penicillanic Acid; Sulfones; Drug Administration Routes; Drug Therapy; Therapeutics; Cephalosporins; Thiazines; Cephaloridine; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Kanamycin; Aminoglycosides; Glycosides; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Officials

• Gabrielle Haeusler

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2021
• First Posted: July 2, 2021
• Study Start: November 15, 2021
• Primary Completion: December 17, 2025
• Study Completion: December 17, 2025
• Last Updated: March 20, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: 6 months following analysis and publication of the primary outcome
• Access Criteria: 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.

Locations

AU (1)