Clinical trial NCT03846804: Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections
Official title: Plasma-Based Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Karius, Inc.
First posted: 2019-02-20
Enrollment: 38
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility 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 (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

Primary outcomes:
measure: Number of Participants With a Pathogen Identified by the Initial Karius Test (IP1) and Standard Culture Methods
timeFrame: Inpatient Sample 1 (IP1) - Within 48 hours of admission
measure: Number of Participants With a Pathogen Identified by the Karius Test (at Time Point IP2) and Standard Culture Methods
timeFrame: Inpatient Sample 2 (IP2) - Within 48 hours of the initial sample
Secondary outcomes:
measure: Microbial Cell Free DNA Level (cfDNA) in Molecules Per Microliter (MPM)
timeFrame: From hospital admission to hospital discharge, up to 3 months
measure: Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP1
timeFrame: Inpatient Sample 1 (IP1) - Within 48 hours of admission
measure: Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP2
timeFrame: Inpatient Sample 2 (IP2) - Within 48 hours of the admission sample
measure: Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Timepoint IP3
timeFrame: Inpatient Sample 3 (IP3) - Within 48 hours of the second inpatient sample
measure: Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP4
timeFrame: Inpatient Sample 4 (IP4) - Within 48 hours of the third inpatient sample
measure: Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP1
timeFrame: Outpatient Sample 1 (OP1) - 1-2 weeks after hospital discharge
measure: Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP2
timeFrame: Outpatient Sample 2 (OP2) - 3-6 weeks after hospital discharge
measure: Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP3
timeFrame: Outpatient Sample 3 (OP3) - 6-8 weeks after hospital discharge
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine - Pediatrics
name: Jack G Schneider, MD
role: PRINCIPAL_INVESTIGATOR
References: