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

• ClinicalTrials.gov Identifier: NCT03846804
• Recruitment Status: Unknown
• First Posted: February 20, 2019
• Last Update Posted: July 5, 2019
• Sponsor: Indiana University
• Collaborator: Karius, Inc.
• Information provided by (Responsible Party): James Wood, Indiana University

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
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
• Estimated 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
• Estimated Study Start Date: September 1, 2019
• Estimated Primary Completion Date: March 15, 2020
• Estimated Study Completion Date: September 30, 2020

Groups and Cohorts

Intervention Details:

• Diagnostic Test: Karius Test
  Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections

Outcome Measures

Primary Outcome Measures :

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

Biospecimen Retention:   Samples With DNA

5ml of whole blood will be collected in a plasma preparation tube (PPT) for NGS testing and centrifuged at 1,100 RCF for 10 minutes at room temperature, within 6 hours of blood draw. Alternatively, for patients in whom 5 ml of blood cannot be drawn, 2ml of blood will drawn in EDTA tubes, centrifuged, and the plasma transferred into sterile polypropylene tubes.

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Children admitted to Riley Hospital for Children (RHC), Indianapolis, Indiana, with clinical presentation consistent with a musculoskeletal infection (osteomyelitis, septic arthritis, or pyomyositis; MSKI).

Criteria

Inclusion Criteria:

1. 6 months (to ensure adequate blood volume drawn) to 18 years of age.
2. 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

Contacts and Locations

Contacts

Contact: James B Wood, MD, MSCI; 317-278-9612; woodjb@iu.edu

Contact: Carrie Nijak, RN; 317-274-8804; canijak@iu.edu

Sponsors and Collaborators

Indiana University

Karius, Inc.

Investigators

• Principal Investigator: James Wood, MD, MSCI; Indiana University School of Medicine - Pediatrics

More Information

• Responsible Party: James Wood, Assistant Professor of Pediatrics, Indiana University
• ClinicalTrials.gov Identifier: NCT03846804
• Other Study ID Numbers: 1901296571
• First Posted: February 20, 2019
• Last Update Posted: July 5, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by James Wood, Indiana University:

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

Additional relevant MeSH terms:

Infections; Communicable Diseases; Osteomyelitis; Arthritis, Infectious; Pyomyositis; Disease Attributes; Pathologic Processes; Arthritis; Joint Diseases; Musculoskeletal Diseases; Bone Diseases, Infectious; Bone Diseases; Suppuration; Myositis; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases