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

Primary Purpose

Musculoskeletal Infection, Acute Hematogenous Osteomyelitis, Septic Arthritis

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Karius Test

About this trial

This is an interventional diagnostic trial for Musculoskeletal Infection focused on measuring infection, plasma based next generation sequencing, blood culture, tissue culture, joint fluid culture, pathogen identification

Eligibility Criteria

6 Months - 18 Years (Child, Adult)All SexesDoes not accept 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.

Exclusion Criteria:

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

Sites / Locations

Riley Hospital for Children

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Karius Test

Arm Description

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

Outcomes

Primary Outcome Measures

Compare pathogen identification of children with musculoskeletal infection using the Karius Test and standard culture methods

Pathogen identification (genus and species) by Karius Test vs. standard culture methods

Compare pathogen identification of children with musculoskeletal infection using the Karius Test and standard culture methods

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

Quantification of cfDNA in molecules per microliter (MPM)

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers at admission

Quantification of cfDNA in molecules per microliter (MPM)

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers

Quantification of cfDNA in molecules per microliter (MPM)

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers

Quantification of cfDNA in molecules per microliter (MPM)

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers

Quantification of cfDNA in molecules per microliter (MPM)

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers

Quantification of cfDNA in molecules per microliter (MPM)

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers

Quantification of cfDNA in molecules per microliter (MPM)

Evaluate whether admission sample quantitative cfDNA predicts severe disease in children with MSKI

Determine the correlation of cfDNA level in MPM to severity of infection

Secondary Outcome Measures

Full Information

NCT ID

NCT03846804

First Posted

February 13, 2019

Last Updated

March 15, 2023

Sponsor

Indiana University

Collaborators

Karius, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03846804

Brief Title

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

Acronym

KDG-002

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

September 1, 2019 (Actual)

Primary Completion Date

June 2, 2022 (Actual)

Study Completion Date

June 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Indiana University

Collaborators

Karius, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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).

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 (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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Karius Test

Arm Type

Experimental

Arm Description

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

Intervention Type

Diagnostic Test

Intervention Name(s)

Karius Test

Intervention Description

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

Primary Outcome Measure Information:

Title

Compare pathogen identification of children with musculoskeletal infection using the Karius Test and standard culture methods

Description

Pathogen identification (genus and species) by Karius Test vs. standard culture methods

Time Frame

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

Title

Compare pathogen identification of children with musculoskeletal infection using the Karius Test and standard culture methods

Description

Pathogen identification (genus and species) by Karius Test vs. standard culture methods

Time Frame

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

Title

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers at admission

Description

Quantification of cfDNA in molecules per microliter (MPM)

Time Frame

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

Title

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers at admission

Description

Quantification of cfDNA in molecules per microliter (MPM)

Time Frame

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

Title

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers

Description

Quantification of cfDNA in molecules per microliter (MPM)

Time Frame

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

Title

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers

Description

Quantification of cfDNA in molecules per microliter (MPM)

Time Frame

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

Title

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers

Description

Quantification of cfDNA in molecules per microliter (MPM)

Time Frame

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

Title

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers

Description

Quantification of cfDNA in molecules per microliter (MPM)

Time Frame

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

Title

Compare the quantity of cfDNA to clinical symptoms and inflammatory markers

Description

Quantification of cfDNA in molecules per microliter (MPM)

Time Frame

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

Title

Evaluate whether admission sample quantitative cfDNA predicts severe disease in children with MSKI

Description

Determine the correlation of cfDNA level in MPM to severity of infection

Time Frame

From hospital admission to hospital discharge, up to 3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jack G Schneider, MD

Organizational Affiliation

Indiana University School of Medicine - Pediatrics

Official's Role

Principal Investigator

Facility Information:

Facility Name

Riley Hospital for Children

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46236

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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