KDG-002: Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections

Sponsor

Indiana University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03846804

Collaborator

Karius, Inc. (Industry)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Musculoskeletal Infection Acute Hematogenous Osteomyelitis Septic Arthritis Osteomyelitis Pyomyositis	Diagnostic Test: Karius Test

Detailed Description

children admitted to Riley Hospital for Children (RHC) with musculoskeletal infections (osteomyelitis, septic arthritis, or pyomyositis) over a 12-month period will be prospectively enrolled. Eligible subjects will be identified by referral from the infectious diseases and orthopedic services at RHC. Blood samples will be obtained on the day of admission (within 48hrs), and 24 hours after the admission sample for real-time NGS testing at Karius Laboratory (Redwood City, CA). If a pathogen is identified by NGS, in either of the first two samples, subsequent samples will be sent every 48-72 hours while inpatient, and then collected every 1-2 weeks after hospital discharge, while being treated for MSKI (maximum 3 follow-up samples). If both of the initial inpatient NGS samples are negative, no further samples will be sent for NGS. Pathogen identification by NGS will be compared to standard cultures methods, and quantitative cfDNA will be evaluated over time.

Study Design

Study Type:

Observational

Anticipated Enrollment :

38 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2019

Anticipated Primary Completion Date :

Mar 15, 2020

Anticipated Study Completion Date :

Sep 30, 2020

Outcome Measures

Primary Outcome Measures

To evaluate and compare pathogen identification of children with musculoskeletalTo compare pathogen identification using the Karius Test and standard culture methods [IP1- Within 48 hours of admission]
Pathogen identification (genus and species) by Karius Test vs. standard culture methods
To evaluate and compare pathogen identification of children with musculoskeletalTo compare pathogen identification using the Karius Test and standard culture methods [IP2- Within 48 hours of the admission sample]
Pathogen identification (genus and species) by Karius Test vs. standard culture methods
Compare the quantity of cfDNA to clinical symptoms and inflammatory markers at admission [IP1- Within 48 hours of admission]
Quantification of cfDNA in molecules per microliter (MPM)
Compare the quantity of cfDNA to clinical symptoms and inflammatory markers at admission [IP2- Within 48 hours of the admission sample]
Quantification of cfDNA in molecules per microliter (MPM)
Compare the quantity of cfDNA to clinical symptoms and inflammatory markers [IP3- Within 48 hours of the second inpatient sample]
Quantification of cfDNA in molecules per microliter (MPM)
Compare the quantity of cfDNA to clinical symptoms and inflammatory markers [IP4- Within 48 hours of the third inpatient sample]
Quantification of cfDNA in molecules per microliter (MPM)
Compare the quantity of cfDNA to clinical symptoms and inflammatory markers [OP1- 1-2 weeks after hospital discharge]
Quantification of cfDNA in molecules per microliter (MPM)
Compare the quantity of cfDNA to clinical symptoms and inflammatory markers [OP2- 3-6 weeks after hospital discharge]
Quantification of cfDNA in molecules per microliter (MPM)
Compare the quantity of cfDNA to clinical symptoms and inflammatory markers [OP3- 6-8 weeks after hospital discharge]
Quantification of cfDNA in molecules per microliter (MPM)
Evaluate whether admission sample quantitative cfDNA predicts severe disease in children with MSKI [From hospital admission to hospital discharge, up to 3 months]
Determine the correlation of cfDNA level in MPM to severity of infection

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

6 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 or CRP.