Host RNA Signature in Children With Cancer and Infection

Host RNA Signature to Discriminate Bacterial From Viral Infection and Non-specific Inflammation in Children With Cancer

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.

Study Overview

• Status: Completed
• Conditions: Childhood Cancer; Infection; Neutropenia, Febrile
• Intervention / Treatment: Diagnostic test: RNA expression signature

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.

• Study Type: Observational
• Enrollment (Actual): 370

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Department of Pediatrics, Aalborg University Hospital
  • Aarhus, Denmark, 8200
    • Department of Pediatric Oncology, Aarhus University Hospital
  • Copenhagen, Denmark, 2100
    • Center for Genomic Medicine
  • Copenhagen, Denmark, 2100
    • Department of pediatric and adolescent medicine, Rigshospitalet (Copenhagen University Hospital)
  • Odense, Denmark, 5000
    • Department of Pediatrics, The H.C. Andersen's Children's hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children with cancer and fever admitted to the Pediatric Oncology Departments throughout Denmark.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; 70 children with cancer and a positive blood culture.	Diagnostic test: RNA expression signature; Whole transcriptome profiling using RNA sequencing
Group 2; 50 children with cancer and no positive blood culture.	Diagnostic test: RNA expression signature; Whole transcriptome profiling using RNA sequencing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RNA signature	To detect specific RNA signatures in whole blood in children with febrile neutropenia	1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time study	An investigation of the change in RNA expression over time during an infection period	1,5 years
Application of known RNA signatures	To test RNA signatures from genes published in other studies eg. the genes IFI44L and FAM89A	1,5 years
Differences in RNA signature according to pathogen	To investigate potential differences in RNA signatures in patients with gram positive versus gram negative bacteria	1,5 years
Comparishment of RNA signatures in neutropenic and non-neutropenic children	To compare RNA signatures in febrile neutropenic and non-neutropenic children with a positive blood culture	1,5 years

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Danish Cancer Society; Lundbeck Foundation; Børnecancerfonden
• Investigators: Principal Investigator: Lotte M. Smedegaard, M.D., ph.d.-student

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): July 31, 2021
• Study Completion (Actual): July 31, 2021

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 16, 2020

Study Record Updates

• Last Update Posted (Estimate): December 22, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Infections; Communicable Diseases; Neutropenia; Febrile Neutropenia
• Other Study ID Numbers: H-2-2010-002_1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No