An interventional study of Karius Test in Musculoskeletal Infection, Acute Hematogenous Osteomyelitis and Septic Arthritis, sponsored by Indiana University. Completed at 1 site in United States. Open to participants aged 6 Months to 18 Years. Per ClinicalTrials.gov, last updated 2023-12-01.
Sponsored by Indiana University · Not applicable, Interventional, and Diagnostic
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).
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.
51 studies on the registry are indexed under Arthritis, Infectious; 12 are open to participants now.
This study's enrollment of 38 is close to the median of 41 across 21 interventional studies indexed under Arthritis, Infectious.
Browse Arthritis, Infectious studies →Indiana University is the lead sponsor of 986 studies on the registry; 198 are open to participants now.
Of its 148 completed or terminated interventional studies of FDA-regulated products, 118 (80%) have results posted.
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Exclusion Criteria:
Participants will have additional blood drawn for the purposes of analysis with the Karius test.
Diagnostic Test: Karius Test
Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections
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.
Time frame: 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"
Time frame: Inpatient Sample 2 (IP2) - Within 48 hours of the initial sample
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.
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
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
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
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
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
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
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
We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).
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
We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).
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
We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).
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
We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).
Time frame: Outpatient Sample 3 (OP3) - 6-8 weeks after hospital discharge
| Milestone | Pediatric Musculoskeletal Infections |
|---|---|
| Started | 38 |
| Completed | 36 |
| Not completed | 2 |
| Withdrew: Refused blood draw | 1 |
| Withdrew: Protocol violation | 1 |
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.
| Participants | Pediatric Musculoskeletal Infections |
|---|---|
| Children with Positive Culture (blood or surgical) | 23 |
| Children with a positive Karius Test (IP1) | 26 |
| Positive agreement between culture and Karius Test (both tests identified the same organism) | 15 |
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"
| Participants | Karius Test |
|---|---|
| Karius Test positive agreement with culture (blood or surgical) | 10 |
| Karius test discordant with culture (any) | 3 |
| Karius test negative | 5 |
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.
| MPM | Karius Test |
|---|---|
| Severe Infection | 408 (358 to 49185) |
| Non-Severe Infection | 322 (92 to 1357) |
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
| Spearman's correlation coefficient | Karius Test |
|---|---|
| MPM vs. CRP | 0.43 |
| MPM vs. ESR | 0.36 |
| MPM vs. WBC | 0.33 |
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
| Spearman's correlation coefficient | Karius Test |
|---|---|
| Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP2 | 0.79 |
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
| Spearman's correlation coefficient | Karius Test |
|---|---|
| Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Timepoint IP3 | 1.0 |
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 coefficient | Karius Test |
|---|---|
| Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP4 | NA |
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 coefficient | Karius Test |
|---|---|
| Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP1 | NA |
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 coefficient | Karius Test |
|---|---|
| Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP2 | NA |
We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).
No measurements were reported for this outcome.
Collected over Through hospital follow up- up to 1 year. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Karius Test | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) |
Children with musculoskeletal infections
| Age, Continuous(years) | Pediatric Musculoskeletal Infections |
|---|---|
| Median | 7 (4 to 12) |
| Sex: Female, Male(Participants) | Pediatric Musculoskeletal Infections |
|---|---|
| Female | 11 |
| Male | 25 |
| Ethnicity (NIH/OMB)(Participants) | Pediatric Musculoskeletal Infections |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 31 |
| Unknown or Not Reported | 4 |
| Race (NIH/OMB)(Participants) | Pediatric Musculoskeletal Infections |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 3 |
| White | 28 |
| More than one race | 0 |
| Unknown or Not Reported | 4 |
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