Early Discontinuation of Antibiotics in Paediatric High-risk Febrile Neutropenia

NCT07590648 | Not Yet Recruiting Phase 4

• 1 other identifier: EU-CT2025-524264-38-00
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this clinical trial is to evaluate whether stopping antibiotic treatment early is safe in paediatric patients with cancer who develop high-risk febrile neutropenia but show good clinical evolution and low biomarker levels 48-72 hours after the episode. The main questions it aims to answer are: Is early discontinuation of antibiotics as safe as the standard strategy in terms of preventing invasive bacterial infections (such as sepsis, microbiologically documented infection, ICU admission, or death)? Does this strategy reduce the number of days on antibiotics without increasing infection-related complications? Researchers will compare early antibiotic discontinuation with the standard care strategy to see whether the early-stop approach provides similar safety while reducing antibiotic exposure. Participants will: Receive standard initial antibiotic therapy for febrile neutropenia. Undergo clinical and biomarker evaluations (including CRP and PCT). Be randomly assigned to: Experimental group: early discontinuation of antibiotics, or Control group: continuation of the standard antibiotic strategy. Be followed for 28 days after randomisation to monitor safety outcomes and treatment effects.

Conditions

Pediatric Cancer; Invasive Bacterial Infection; Febrile Neutropenia (FN); Hematologic Malignancies; Solid Tumors

Keywords

Febrile Neutropenia; Pediatric Oncology; Hematologic Malignancies; Solid Tumors; Invasive Bacterial Infection; Antibiotic Discontinuation; Antibiotic Stewardship; Biomarkers (CRP, PCT, IL-8); Early Stop Strategy; Randomized Clinical Trial; Non-Inferiority Trial; Neutropenia

Outcome Measures

Primary Outcomes (1)

• Composite rate of adverse outcomes attributable to invasive or clinically significant bacterial infection

  Composite endpoint including any of the following events: death, pediatric intensive care unit admission, sepsis or septic shock, microbiologically documented bacterial infection, or radiologically confirmed pneumonia. The proportion of participants experiencing at least one component of the composite endpoint will be compared between the early discontinuation arm and the standard continuation arm to assess non-inferiority in safety.

  Day 0 (randomization) to Day 28

Secondary Outcomes (6)

• Number of days of antibiotic therapy

  From Day 0 to Day 28

• Incidence of antibiotic-related adverse events

  Up to Day 28

• Predictive performance of C-reactive protein (CRP) for invasive bacterial infection

  Measured at episode onset, at 48-72 hours, and optionally on Day 5

• Predictive performance of procalcitonin (PCT) for invasive bacterial infection

  Measured at episode onset, at 48-72 hours, and optionally on Day 5

• Predictive performance of interleukin-8 (IL-8) for invasive bacterial infection

  Measured at episode onset and at 48-72 hours

Study Arms (2)

Early Discontinuation of Antibiotics

EXPERIMENTAL

Participants assigned to this arm will have intravenous antibiotic therapy discontinued within 24 hours after randomization, provided they meet all clinical stability and low-risk criteria. Patients may be discharged if no other clinical reasons require hospitalization. Antibiotics may be reintroduced if fever recurs or if clinical deterioration suggests infection.

Drug: Early Discontinuation of Antibiotics

Standard Antibiotic Strategy

ACTIVE COMPARATOR

Participants assigned to this arm will continue antibiotic therapy for at least 7 days and/or until signs of marrow recovery are present (ANC ≥100/mm³), according to each center's standard protocol. Hospital discharge will occur once clinical criteria permit.

Drug: Standard Antibiotic Continuation Strategy

Interventions

Early Discontinuation of Antibiotics DRUG

Participants assigned to this intervention will stop intravenous antibiotic therapy within 24 hours after randomization, provided they meet all required clinical stability and low-risk criteria at 48-72 hours (or day 5) after the febrile neutropenia episode. Patients may be discharged once clinically appropriate. Antibiotics may be restarted if fever recurs or clinical deterioration suggests infection.

Also known as: Drug stop within 24 hours after randomization:Piperacillin-tazobactam, amikacin, meropenem, cefepime, ceftazidime, vancomycin, teicoplanin, ciprofloxacin, levofloxacine and metronidazole

Early Discontinuation of Antibiotics

Standard Antibiotic Continuation Strategy DRUG

Continuation of antibiotic therapy for at least 7 days and/or until marrow recovery (ANC ≥100/mm³) following standard institutional protocols. Therapy may be extended depending on clinical assessment.

Also known as: Drug continuation for at least 7d and/or until marrow recovery:Piperacillin-tazobactam,amikacin,meropenem,cefepime, ceftazidime, vancomycin, teicoplanin, ciprofloxacin, levofloxacine and metronidazole

Standard Antibiotic Strategy

Eligibility Criteria

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

You may qualify if:

• Male and female patients ≤18 years of age expected to develop prolonged neutropenia (\>7 days), with:
• Acute myeloblastic leukaemia at any phase of chemotherapy
• Acute lymphoblastic leukaemia in induction, consolidation, or intensification phases
• Biphenotypic leukaemia at any phase of chemotherapy
• Lymphoblastic lymphoma in induction and consolidation phases
• B-cell and anaplastic lymphoma receiving high-intensity chemotherapy
• Solid tumours receiving high-intensity chemotherapy
• Relapsed leukaemia at any phase of treatment
• Episode of febrile neutropenia (FN), defined as a single axillary temperature ≥38.0°C in a patient with an absolute neutrophil count (ANC) \<500 neutrophils/mm³, or expected to fall below this value within the next 48-72 hours.
• Antibiotic treatment initiated for the current FN episode (routine antimicrobial prophylaxis is allowed, as well as teicoplanin 3 days/week for patients with AML included in the CHIP-AML-2022 protocol and therefore in the Pro-teico study).
• Low risk of invasive bacterial infection (IBI) at the start of the FN episode. Patients must meet all of the following:
• CRP \<9 mg/dL
• PCT \<0.5 ng/mL
• Absence of hypotension
• No microbiologically documented bacterial infection 48-72 hours after the FN episode.

You may not qualify if:

• Antibiotic treatment at the time of the FN episode different from that used prophylactically.
• Empirical antibiotic treatment different from that recommended in international guidelines.
• Patient with poor clinical evolution during the first 12 hours (hemodynamic instability, PICU admission, death).
• Active participation in the same study at the onset of the current FN episode.
• Active participation in another clinical trial that, in the investigators' opinion, may interfere with the assessment of the results.
• Any condition which, in the investigator's opinion, makes study participation unsuitable for the patient or could limit, prevent, or confound the assessments planned in the protocol.
• Female patients who are pregnant or breastfeeding

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead

Study Sites (4)

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

Location

Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Hospital Infantil Universitario Niño Jesús

Madrid, Madrid, 28009, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Related Publications (19)

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MeSH Terms

Conditions

Febrile Neutropenia; Neoplasms; Hematologic Neoplasms; Neutropenia

Interventions

Amikacin; Meropenem; Cefepime; Ceftazidime; Vancomycin; Teicoplanin; Ciprofloxacin; Ofloxacin; Metronidazole

Condition Hierarchy (Ancestors)

Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Kanamycin; Aminoglycosides; Glycosides; Carbohydrates; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cephalosporins; Thiazines; Sulfur Compounds; Cephaloridine; Glycopeptides; Glycoconjugates; Peptides; Amino Acids, Peptides, and Proteins; Lipoglycopeptides; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Natalia A Mendoza Palomar, MD

CONTACT

+34 934893000; nataliaana.mendoza@vallhebron.cat

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: February 16, 2026
• First Posted: May 15, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 15, 2026

Record last verified: 2026-05

Locations

ES (4)