Musculoskeletal InfectionKDG-002NCT03846804
Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections
A study testing Karius Test in people with Musculoskeletal Infection and Acute Hematogenous Osteomyelitis, run by Indiana University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Musculoskeletal Infection, Acute Hematogenous Osteomyelitis, Septic Arthritis
- What is being tested?
- Karius Test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2019to 2 Jun 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
Who cannot join
- Subjects will be excluded if they have clinical evidence suggesting an alternative diagnosis; inability or unwillingness to consent for the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Riley Hospital for Children
Indianapolis, Indiana, 46202
About this study
Official title: Plasma-Based 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).
Read the 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.
- Conditions
- Musculoskeletal Infection, Acute Hematogenous Osteomyelitis, Septic Arthritis, Osteomyelitis, Pyomyositis
- Being tested
- Karius Test
- Keywords
- infection, plasma based next generation sequencing, blood culture, tissue culture, joint fluid culture, pathogen identification
- Medical subject headings
- Arthritis, Infectious, Osteomyelitis, Pyomyositis, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Karius TestDiagnostic test
Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections
| Study group | Role | What they receive |
|---|---|---|
| Karius Test | Experimental | Participants will have additional blood drawn for the purposes of analysis with the Karius test. Receives: Diagnostic Test: Karius Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Pathogen Identified by the Initial Karius Test (IP1) and Standard Culture Methods
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.
Measured: Inpatient Sample 1 (IP1) - Within 48 hours of admission
Number of Participants With a Pathogen Identified by the Karius Test (at Time Point IP2) and Standard Culture Methods
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"
Measured: Inpatient Sample 2 (IP2) - Within 48 hours of the initial sample
Secondary outcomes (8)
Microbial Cell Free DNA Level (cfDNA) in Molecules Per Microliter (MPM)
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.
Measured: From hospital admission to hospital discharge, up to 3 months
Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP1
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
Measured: Inpatient Sample 1 (IP1) - Within 48 hours of admission
Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP2
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
Measured: Inpatient Sample 2 (IP2) - Within 48 hours of the admission sample
Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Timepoint IP3
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
Measured: Inpatient Sample 3 (IP3) - Within 48 hours of the second inpatient sample
Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP4
We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).
Measured: Inpatient Sample 4 (IP4) - Within 48 hours of the third inpatient sample
Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP1
We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).
Measured: Outpatient Sample 1 (OP1) - 1-2 weeks after hospital discharge
Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP2
We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).
Measured: Outpatient Sample 2 (OP2) - 3-6 weeks after hospital discharge
Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP3
We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).
Measured: Outpatient Sample 3 (OP3) - 6-8 weeks after hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2019
- Study start1 Sep 2019
- Primary completion2 Jun 2022
- Study completion2 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Musculoskeletal InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- Karius, Inc.
- Responsible party
- Principal investigator, Jack Schneider, Indiana University
- Investigators
- Jack G Schneider, MD, Principal investigator, Indiana University School of Medicine - Pediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03846804
- Sponsor's protocol ID
- 1901296571
- Acronym
- KDG-002
- Status last verified
- Nov 2023
- First submitted
- 13 Feb 2019
- Last updated
- 1 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma-Based Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections
- ClinicalTrials.gov ID
- NCT03846804
- Acronym / sponsor ID
- KDG-002 / 1901296571
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Karius, Inc.
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 2 Jun 2022 (actual)
- Study completion
- 2 Jun 2022 (actual)
- First posted
- 20 Feb 2019 (actual)
- Results
- Posted 1 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Karius Test | Experimental | Diagnostic Test: Karius TestParticipants will have additional blood drawn for the purposes of analysis with the Karius test. |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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).
Key exclusion criteria (1 listed)
- Subjects will be excluded if they have clinical evidence suggesting an alternative diagnosis; inability or unwillingness to consent for the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Karius TestNext-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections | Diagnostic test | Karius Test |
Primary outcome
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.
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"
8 secondary outcomes
Microbial Cell Free DNA Level (cfDNA) in Molecules Per Microliter (MPM)
Time frame: From hospital admission to hospital discharge, up to 3 months
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
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
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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jack G Schneider, MD principal investigator
Indiana University School of Medicine - Pediatrics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Karius Test in people with Musculoskeletal Infection and Acute Hematogenous Osteomyelitis, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2023.