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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04637464
Recruitment Status : Recruiting
First Posted : November 19, 2020
Last Update Posted : November 19, 2020
Sponsor:
Information provided by (Responsible Party):
Kjeld Schmiegelow, Rigshospitalet, Denmark

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.


Condition or disease Intervention/treatment Phase
Neutropenia, Febrile Pediatric Cancer Other: Early termination of empirical antibiotics Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

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.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Early Termination of Empirical Antibiotics in High-risk Febrile Neutropenia in Children With Cancer: an Open-label, Randomised, Controlled Trial
Estimated Study Start Date : November 20, 2020
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : September 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics Fever

Arm Intervention/treatment
Experimental: Experimental group

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

No Intervention: Control group
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



Primary Outcome Measures :
  1. Days without antibiotics [ Time Frame: 28 days from randomization ]
    Number of days without antibiotic treatment


Secondary Outcome Measures :
  1. Mortality [ Time Frame: 28 days from randomization ]
    Crude mortality

  2. Severe adverse events [ Time Frame: 28 days from randomization ]
    Severe adverse events

  3. New episode of neutropenic fever [ Time Frame: 28 days from randomization ]
    New episode of neutropenic fever

  4. Days with fever [ Time Frame: 28 days from randomization ]
    Days with fever

  5. Time to bone marrow recovery [ Time Frame: Patients are monitored for when this has happened up to three months after randomisation ]
    Time to bone marrow recovery

  6. Time to next chemotherapy [ Time Frame: Patients are monitored for when this has happened up to three months after randomisation ]
    Time to next chemotherapy

  7. Alterations in gut microbiome [ Time Frame: At day 28 days after randomization ]
    Alterations in gut microbiome composition measured by bacterial whole genome sequencing on fecal samples collected at 28 days after randomisation.



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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (for each episode):

  1. patient with cancer aged 18 years or below,
  2. absolute neutrophil count below 0.5x10⁹/L with expected duration of neutropenia for more than 7 days, and
  3. 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).

Exclusion Criteria (for each episode):

  1. 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),
  2. obvious non-infectious causes of fever (e.g. drug and transfusion related),
  3. children requiring prophylactic antibacterial antibiotics according to protocol besides co-trimoxazole for Pneumocystis jirovecii after the febrile episode.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04637464


Contacts
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Contact: Nadja Vissing, MD, PhD +4535451312 nadja.hawwa.vissing@regionh.dk
Contact: Ulrikka Nygaard, MD, PhD +4535459761 ulrikka.nygaard@regionh.dk

Locations
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Denmark
Aarhus University Hospital Skejby Not yet recruiting
Aarhus, Denmark, 8200
Contact: Birgitte Klug Albertsen, MD PhD    +4578451482    biralber@rm.dk   
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Nadja Vissing, MD PhD    +4535451312    nadja.hawwa.vissing@regionh.dk   
Odense Univesity Hospital Not yet recruiting
Odense, Denmark, 5000
Contact: Peder Skov Wehner, MD PhD    +4565412078    Peder.Skov.Wehner@rsyd.dk   
Sponsors and Collaborators
Kjeld Schmiegelow
Investigators
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Principal Investigator: Nadja Vissing, MD, PhD Rigshospitalet, Denmark
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Responsible Party: Kjeld Schmiegelow, Professor in Paediatrics, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT04637464    
Other Study ID Numbers: EarlyTerm
First Posted: November 19, 2020    Key Record Dates
Last Update Posted: November 19, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neutropenia
Febrile Neutropenia
Fever
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Body Temperature Changes
Anti-Bacterial Agents
Anti-Infective Agents