Clinical trial NCT04669418: Host RNA Signature in Children With Cancer and Infection
Official title: Host RNA Signature to Discriminate Bacterial From Viral Infection and Non-specific Inflammation in Children With Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Childhood Cancer
Infection
Neutropenia, Febrile
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Børnecancerfonden
name: Lundbeck Foundation
name: Danish Cancer Society
First posted: 2020-12-16
Enrollment: 370
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children with cancer and fever admitted to the Pediatric Oncology Departments throughout Denmark.

Brief summary: The aim is to investigate if RNA expression signature can discriminate bacterial from viral infection or non-infectious inflammation in children with cancer.

Earlier studies in immunocompetent children have shown promising results, but studies in immunocompromised children are lacking.

We aim to include 300 febrile episodes in children with cancer. The samples will be analysed by RNA sequencing. If succesfull, this method can help prevent unnecessary antibiotic treatment, reduce hospital admissions, side effects and antimicrobial resistance and improve quality of life for children during cancer treatment.

Detailed description: Children with cancer are at high risk of invasive bacterial infections particularly during neutropenia. Febrile neutropenia is an early sign of a potentially fatal infection requiring broad-spectrum empiric antibiotics. However, the majority of children do not have a bacterial infection, but still receive antibiotics, since current tests cannot distinguish causes of fever. A number of transcriptomic studies of immunocompetent patients show that host leukocyte patterns of activated RNA can discriminate bacterial infection from non-infectious inflammation with high accuracy, but studies in immunocomprised patients are few.

Methods

A prospective non-interventional observational multicentre study including febrile childhood cancer patients during 24 months at all Danish Pediatric Oncology Departments (Rigshospitalet, Aarhus, Odense and Aalborg University Hospitals). Leukocyte RNA expression will be analysed in whole blood samples by RNA sequencing adjusted for low RNA input. 300 febrile episodes will be included, and predictive host RNA signatures will be identified in a discovery cohort and assessed in a validation cohort. Further, to explore the transcriptome in non-febrile children with neutropenia, we include a control group of 15 children with cancer and no fever.

Time frame Inclusion of children: 1st of June 2019 to 31st of May 2021 Analysis of samples (RNA sequencing): 1st of June 2021 - 1st of December 2021

Perspective

The study will create a base for a randomised trial regarding implementation of RNA signature versus normal procedure in handling febrile children with cancer. This can lead to the development of a targeted RNA-expression analytical platform that can prevent unnecessary antibiotic treatment in the majority of children with febrile neutropenia. This will reduce hospital admissions, side effects, antimicrobial resistance and improve quality of life during cancer treatment. The results can be extrapolated to the adult patients with cancer, who are often treated with prophylactic antibiotics, which complicate finding the infectious agent. Additionally, the test may be applied in other immunosuppressed children with infections.

Eligibility criteria: Inclusion Criteria:

Children with cancer and fever. Fever defined as temperature above 38.5 °C measured once, or 38.0-38.5 °C for ≥ 1 hour.

Exclusion Criteria:

The children can be excluded if they turn out to have a different diagnosis than expected or if it is not possible to draw the blood tests.

Primary outcomes:
measure: RNA signature
timeFrame: 1.5 years
Secondary outcomes:
measure: Time study
timeFrame: 1,5 years
measure: Application of known RNA signatures
timeFrame: 1,5 years
measure: Differences in RNA signature according to pathogen
timeFrame: 1,5 years
measure: Comparishment of RNA signatures in neutropenic and non-neutropenic children
timeFrame: 1,5 years
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Pediatrics, Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Department of Pediatric Oncology, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Center for Genomic Medicine
city: Copenhagen
country: Denmark
facility: Department of pediatric and adolescent medicine, Rigshospitalet (Copenhagen University Hospital)
city: Odense
country: Denmark
facility: Department of Pediatrics, The H.C. Andersen's Children's hospital
Study officials:
affiliation: ph.d.-student
name: Lotte M. Smedegaard, M.D.
role: PRINCIPAL_INVESTIGATOR
References: