Host RNA Signature in Children With Cancer and Infection

Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04669418
• Other study ID #: H-2-2010-002_1
• Status: Completed
• Start date: June 1, 2019
• Est. completion date: July 31, 2021

Study information

• Verified date: December 2022
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 370
• Est. completion date: July 31, 2021
• Est. primary completion date: July 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Childhood Cancer
• Communicable Diseases
• Febrile Neutropenia
• Infection
• Infections
• Neutropenia
• Neutropenia, Febrile

Intervention

Diagnostic Test:
• RNA expression signature
Whole transcriptome profiling using RNA sequencing

Locations

Country	Name	City	State
Denmark	Department of Pediatrics, Aalborg University Hospital	Aalborg
Denmark	Department of Pediatric Oncology, Aarhus University Hospital	Aarhus
Denmark	Center for Genomic Medicine	Copenhagen
Denmark	Department of pediatric and adolescent medicine, Rigshospitalet (Copenhagen University Hospital)	Copenhagen
Denmark	Department of Pediatrics, The H.C. Andersen's Children's hospital	Odense

Sponsors (4)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Børnecancerfonden, Danish Cancer Society, Lundbeck Foundation

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	RNA signature	To detect specific RNA signatures in whole blood in children with febrile neutropenia	1.5 years
Secondary	Time study	An investigation of the change in RNA expression over time during an infection period	1,5 years
Secondary	Application of known RNA signatures	To test RNA signatures from genes published in other studies eg. the genes IFI44L and FAM89A	1,5 years
Secondary	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
Secondary	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