Host RNA Profiles to Detect Infections in Young Infants (CHILD_YIC)

This study seeks to identify and test host RNA expression profiles as markers for infections in young infants. Preliminary studies have shown high sensitivity and specificity for the discrimination of bacterial from non-bacterial infections in children, but the method has only been investigated in a limited number of young infants. The study aims to include 65 young infants with serious bacterial infections. The samples will be analysed by RNA sequencing. New diagnostic tools may help reduce unnecessary antibiotic treatment, antibiotic resistance, side-effects, hospitalisation and invasive procedures.

Study Overview

• Status: Completed
• Conditions: Sepsis; Bacterial Infections; Fever; Bacteremia; Urinary Tract Infections; Meningitis; Infant, Newborn, Disease; Viral Infection

Detailed Description

Background:

Infections in young infants is a challenge as 1) it is often not possible to distinguish serious bacterial infection (SBI) from viral infection by clinical appearance alone, 2) a causative organism is often not identified and 3) due to relatively low sensitivity and specificity of current biomarkers. The consequence is overtreatment with antibiotics being prescribed to as many as 50% of febrile young infants presenting to emergency departments. However, the majority of these children does not have a bacterial infection. Host RNA expression profiling has shown high sensitivity and specificity for discriminating bacterial from non-bacterial infections in preliminary studies of febrile young infants.

Methods:

A prospective multicentre observational study including young infants admitted and evaluated due to suspected infection at the 4 paediatric acute care units in the Capital Region of Denmark (Rigshospitalet, Hvidovre Hospital, Herlev Hospital, Nordsjællands Hospital - Hillerød). Whole blood will be collected in PAXgene blood RNA tubes and analysed by RNA sequencing at the Centre for Genomic Medicine, Rigshospitalet. Host RNA expression profiles will be identified in a discovery cohort and the diagnostic performance will be tested in a validation cohort. A control group of healthy and afebrile young infants will be included.

Time frames:

Patient recruiting: May 15th 2020 to February 28th 2022. Sample analysis (RNA sequencing): March 1st 2022 to August 31st 2022.

Perspectives:

New molecular-based diagnostic tools complementary to conventional methods may optimise infection management in young infants by improving early diagnostics and allowing early modification of antibiotic treatment. This will reduce antibiotic resistance, side effects, unnecessary hospitalisation and invasive procedures.

• Study Type: Observational
• Enrollment (Actual): 152

Contacts and Locations

• Study Contact: Name: Kia Hee Schultz Dungu, MD; Phone Number: +45 22645782; Email: kia.hee.schultz.dungu@regionh.dk
• Study Contact Backup: Name: Ulrikka Nygaard, Ass Prof PhD; Phone Number: +45 35459761; Email: Ulrikka.Nygaard@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Department of Paediatrics and Adolescent Medicine, Rigshospitalet
  • Herlev, Denmark, 2730
    • Department of Paediatrics and Adolescent Medicine, Herlev Hospital
  • Hillerød, Denmark, 3400
    • Department of Paediatrics and Adolescent Medicine, Nordsjællands Hospital - Hillerød
  • Hvidovre, Denmark, 2650
    • Department of Paediatrics, Hvidovre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Young infants suspected of infection and admitted to one of the 4 paediatric departments in the Capital Region of Denmark.

Description

Inclusion Criteria:

1. age 0-3 months
2. admitted from home
3. suspected of infection
4. having routine blood sampling done
5. gestational age or corrected gestational age greater than or equal to 37+0
6. informed consent

Exclusion Criteria:

1. not possible to draw blood tests
2. withdrawal of consent
3. sampling >48 hours after admission

Study Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1; 70 young infants with proven bacterial infection. Interventions: Diagnostic test: Host RNA expression profiling (whole transcriptome profiling) using whole blood RNA sequencing. Cases will be randomly assigned to a "Discovery Cohort" (identification of diagnostic RNA profiles) or a "Validation Cohort" (validation of the identified RNA profiles).
Group 2; 70 young infants with non-bacterial infection. Interventions: Diagnostic test: Host RNA expression profiling (whole transcriptome profiling) using whole blood RNA sequencing. Cases will be randomly assigned to a "Discovery Cohort" (identification of diagnostic RNA profiles) or a "Validation Cohort" (validation of the identified RNA profiles).
Group 3; 30 young infants without infection. Interventions: Diagnostic test: Host RNA expression profiling (whole transcriptome profiling) using whole blood RNA sequencing. Cases will be randomly assigned to a "Discovery Cohort" (identification of diagnostic RNA profiles) or a "Validation Cohort" (validation of the identified RNA profiles).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Host RNA expression profiles	To identify specific host RNA expression profiles in whole blood in response to bacterial infections in young infants	21 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Application of known host RNA profiles	To test host RNA profiles published in other studies, e.g. based on the genes IFI44L and FAM89A	21 months
Time study	To investigate the change in host RNA expression over time during an infection period	21 months

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Kia Hee Schultz Dungu, MD, Rigshospitalet, Denmark; Study Chair: Ulrikka Nygaard, Ass Prof PhD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2020
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (Actual): March 30, 2021

Study Record Updates

• Last Update Posted (Estimate): December 28, 2022
• Last Update Submitted That Met QC Criteria: December 25, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Bacterial Infections and Mycoses; Sepsis; Infections; Communicable Diseases; Virus Diseases; Bacteremia; Urinary Tract Infections; Meningitis; Bacterial Infections; Infant, Newborn, Diseases
• Other Study ID Numbers: H-18065635-YIC

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