Early Termination of Empirical Antibiotics in Febrile Neutropenia in Children With Cancer

NCT04637464 | Completed DMC

• 1 other identifier: EarlyTerm
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 3

Brief Summary

The study is a nationwide, multicenter, open label, randomized controlled trial. A target population of 220 children in treatment for cancer with neutropenic fever and a neutrophil count below 0.5 × 10⁹ cells/L with expected duration for more than 7 days will be recruited during the first 48 hours of antibiotic treatment (24 months inclusion period). They will be randomized 1:1 as follows:

• Experimental group: Discontinuation of antibiotics, despite neutrophil count below 0.5 × 10⁹ cells/L, after 48 hours of apyrexia and clinical stability
• Control group: Discontinuation of antibiotics when neutrophil count is equal to or above 0.5 × 10⁹ cells/L and the child is afebrile and clinically stable (up to maximum of 14 days after apyrexia and clinical stability). Primary endpoint is the number of days without antibiotic treatment in 28 days after treatment initiation. Secondary endpoints are crude mortality, severe adverse events, days with relapsing fever, and alterations of the microbiome.

Conditions

Neutropenia, Febrile; Pediatric Cancer

Outcome Measures

Primary Outcomes (1)

• Days without antibiotics

  Number of days without antibiotic treatment

  28 days from randomization

Secondary Outcomes (7)

• Mortality

  28 days from randomization

• Severe adverse events

  28 days from randomization

• New episode of neutropenic fever

  28 days from randomization

• Days with fever

  28 days from randomization

• Time to bone marrow recovery

  Patients are monitored for when this has happened up to three months after randomisation

Study Arms (2)

Experimental group

EXPERIMENTAL

Discontinuation of empirical antibiotics, despite neutrophil count below 0.5x10⁹ cells/L, after 48 hours of apyrexia and clinical stability. A child is considered clinically stable when there is resolution of all symptoms and signs of infection, and normalization of vital signs including heart rate, respiratory rate, oxygen saturation, blood pressure, and daily diuresis.

Other: Early termination of empirical antibiotics

Control group

NO INTERVENTION

Discontinuation of antibiotics when neutrophil count is equal to or above 0.5x10⁹ cells/L, and the child is afebrile and clinical stable OR the child has received 10 days of antibiotics and have been afebrile and clinically stable for 7 days

Interventions

Early termination of empirical antibiotics OTHER

Termination of empirical antibiotics for febrile neutropenia based on clinical parameters, regardless of neutrophile count.

Experimental group

Eligibility Criteria

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

You may qualify if:

• patient with cancer aged 18 years or below,
• absolute neutrophil count below 0.5x10⁹/L with expected duration of neutropenia for more than 7 days, and
• a single temperature of at least 38.5°C, or a temperature above 38.0°C sustained over a 1-hour period (auricular, oral or rectal).

You may not qualify if:

• known etiology of fever, defined by a clinically significant positive culture (blood, urine, tracheal) collected during the feverish episode or a clinically documented focal infection despite negative cultures (e.g. pneumonia and cellulitis),
• obvious non-infectious causes of fever (e.g. drug and transfusion related),
• children requiring prophylactic antibacterial antibiotics according to protocol besides co-trimoxazole for Pneumocystis jirovecii after the febrile episode.

Sponsors & Collaborators

• Kjeld Schmiegelow: lead

Study Sites (3)

Aarhus University Hospital Skejby

Aarhus, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Odense Univesity Hospital

Odense, 5000, Denmark

Location

MeSH Terms

Conditions

Febrile Neutropenia; Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Nadja Vissing, MD, PhD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor in Paediatrics

Model Details: Patients receiving empirical antibiotic treatment due to high risk neutropenic fever will be randomly assigned 1:1 to one of two groups regimens. Randomization can occur from 36 hours after initiation of antibiotics until 48 hours of apyrexia and clinical stability. The allocated treatment regimen is followed from randomization until neutrophil recovery, also in case of relapsing fever after termination of antibiotic treatment. A participant can be randomized more than once, but only one time during each episode of neutropenia, i.e. bone marrow recovery and subsequent chemotherapy treatment must have taken place before a new randomization can occur.

Study Record Dates

• First Submitted: November 6, 2020
• First Posted: November 19, 2020
• Study Start: November 20, 2020
• Primary Completion: January 31, 2025
• Study Completion: March 11, 2025
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (3)