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Completed

NCT Number: NCT03846804

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

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).

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Key information

Conditions

Musculoskeletal Infection Acute Hematogenous Osteomyelitis Arthritis Arthritis, Infectious Bone Diseases Bone Diseases, Infectious Infections Joint Diseases Muscular Diseases Musculoskeletal Diseases Myositis Nervous System Diseases Neuromuscular Diseases Osteomyelitis Pyomyositis Septic Arthritis Suppuration

Age range

6 month–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

About this study

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 (next-generation sequencing) 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 (cell-free DNA) will be evaluated over time.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 (erythrocyte sedimentation rate) or CRP (C-reactive protein).

Exclusion criteria

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

Treatment and study plan

Karius Test

Diagnostic Test

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

Primary outcomes

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

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

    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.

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

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

    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"

Secondary outcomes

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

    Time frame: From hospital admission to hospital discharge, up to 3 months

    We compared the microbial cfDNA level (on initial samples, IP1) between patients with non-severe MSKI to those with severe MSKI (defined as need for intensive care unit (ICU) care; infection in two or more non-contiguous anatomic sites (disseminated disease); need for more than 1 debridement procedure; deep vein thrombosis or thromboembolic disease; or pathologic fracture).

    Only those with a positive agreement between initial Karius Test (IP1) and culture were analyzed (n=15).

    Mann-Whitney U was used to compare median microbial cfDNA between those with non-severe vs. severe MSKI.

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

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

    We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC), common inflammatory markers followed in children with MSKI.

    Spearman's correlation was used to compare the MPM value to the CRP, ESR and WBC

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

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

    We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).

    Spearman's correlation was used to compare the MPM value to the CRP

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

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

    We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI) at time point IP3 in participants with positive agreement between the Karius Test and culture.

    Spearman's correlation was used to compare the MPM value to the CRP

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

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

    We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).

  6. Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP1

    Time frame: Outpatient Sample 1 (OP1) - 1-2 weeks after hospital discharge

    We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).

  7. Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP2

    Time frame: Outpatient Sample 2 (OP2) - 3-6 weeks after hospital discharge

    We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).

  8. Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP3

    Time frame: Outpatient Sample 3 (OP3) - 6-8 weeks after hospital discharge

    We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).

Sponsors and collaborators

Lead sponsor

Indiana University

Other

Collaborators

  • Karius, Inc.

Registry information

Official study title

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

Acronym: KDG-002

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Feb 20, 2019
Registry last updated
Dec 1, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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