Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections

NCT03846804 | Completed Results FDA Device

• 1 other identifier: 1901296571
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the use of a blood test: Karius® plasma-based next-generation sequencing test (Karius Test), to see if we can detect and measure the infection causing agent in children with musculoskeletal infections (MSKI).

Conditions

Musculoskeletal Infection; Acute Hematogenous Osteomyelitis; Septic Arthritis; Osteomyelitis; Pyomyositis

Keywords

infection; plasma based next generation sequencing; blood culture; tissue culture; joint fluid culture; pathogen identification

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Pathogen Identified by the Initial Karius Test (IP1) and Standard Culture Methods

  We evaluated the total number of participants that had a pathogen identified by the initial (IP1) Karius Test ("positive Karius Test"). We compared the results of the Karius Test to cultures (gold standard) for each participant. Karius Test results that matched cultures results (same genus and species) were considered "positive agreement". We also evaluated at the number of participants who had negative cultures, but had a positive Karius Test.

  Inpatient Sample 1 (IP1) - Within 48 hours of admission

• Number of Participants With a Pathogen Identified by the Karius Test (at Time Point IP2) and Standard Culture Methods

  We evaluated the total number of participants that had a pathogen identified by the Karius Test ("positive Karius Test") at time point IP2 (within 48 hours of the initial sample). We compared the results of the Karius Test to those with a positive culture (gold standard) for each participant. Karius Test results that matched cultures results (same genus and species) were considered "positive agreement". Karius Test results that identified an organism different from the organism identified in culture were considered "discordant results" Karius Tests results that did not identify any organism were consider "negative"

  Inpatient Sample 2 (IP2) - Within 48 hours of the initial sample

Secondary Outcomes (8)

• Microbial Cell Free DNA Level (cfDNA) in Molecules Per Microliter (MPM)

  From hospital admission to hospital discharge, up to 3 months

• Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP1

  Inpatient Sample 1 (IP1) - Within 48 hours of admission

• Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP2

  Inpatient Sample 2 (IP2) - Within 48 hours of the admission sample

• Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Timepoint IP3

  Inpatient Sample 3 (IP3) - Within 48 hours of the second inpatient sample

• Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP4

  Inpatient Sample 4 (IP4) - Within 48 hours of the third inpatient sample

Study Arms (1)

Karius Test

EXPERIMENTAL

Participants will have additional blood drawn for the purposes of analysis with the Karius test.

Diagnostic Test: Karius Test

Interventions

Karius Test DIAGNOSTIC_TEST

Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections

Karius Test

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• months (to ensure adequate blood volume drawn) to 18 years of age.
• Strong clinical suspicion of MSKI as evidenced by fever, osteoarticular pain (e.g. tenderness to palpation of a joint, bone pain, or refusal to bear weight); and elevated ESR (erythrocyte sedimentation rate) or CRP (C-reactive protein).

You may not qualify if:

• Subjects will be excluded if they have clinical evidence suggesting an alternative diagnosis; inability or unwillingness to consent for the study

Sponsors & Collaborators

• Indiana University: lead
• Karius, Inc.: collaborator

Study Sites (1)

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Arthritis, Infectious; Osteomyelitis; Pyomyositis; Infections

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Bone Diseases, Infectious; Bone Diseases; Suppuration; Myositis; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases

Limitations and Caveats

The number of participants with the data for the secondary outcomes was very small, thus all of the secondary outcomes were underpowered to show a statistical difference. For secondary outcomes 7,8, and 9, there was not enough data to do the analyses. For secondary outcome 10, no patient data was collected because no patients followed up at this time point.

Results Point of Contact

• Title: James Wood, MD
• Organization: Indiana University School of Medicine

woodjb@iu.edu

317-944-7260

Study Officials

• Jack G Schneider, MD

  Indiana University School of Medicine - Pediatrics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine and Clinical Pediatrics

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: February 20, 2019
• Study Start: September 1, 2019
• Primary Completion: June 2, 2022
• Study Completion: June 2, 2022
• Last Updated: December 1, 2023
• Results First Posted: December 1, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)