Ignite Creation Date:
2025-12-24 @ 9:11 PM
Ignite Modification Date:
2026-01-04 @ 8:09 AM
Study NCT ID:
NCT03846804
Status:
COMPLETED
Last Update Posted:
2023-12-01
First Post:
2019-02-13
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2023-08-23', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D001170', 'term': 'Arthritis, Infectious'}, {'id': 'D010019', 'term': 'Osteomyelitis'}, {'id': 'D052880', 'term': 'Pyomyositis'}, {'id': 'D007239', 'term': 'Infections'}], 'ancestors': [{'id': 'D001168', 'term': 'Arthritis'}, {'id': 'D007592', 'term': 'Joint Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D001850', 'term': 'Bone Diseases, Infectious'}, {'id': 'D001847', 'term': 'Bone Diseases'}, {'id': 'D013492', 'term': 'Suppuration'}, {'id': 'D009220', 'term': 'Myositis'}, {'id': 'D009135', 'term': 'Muscular Diseases'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'woodjb@iu.edu', 'phone': '317-944-7260', 'title': 'James Wood, MD', 'organization': 'Indiana University School of Medicine'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'The number of participants with the data for the secondary outcomes was very small, thus all of the secondary outcomes were underpowered to show a statistical difference. For secondary outcomes 7,8, and 9, there was not enough data to do the analyses. For secondary outcome 10, no patient data was collected because no patients followed up at this time point.'}}, 'adverseEventsModule': {'timeFrame': 'Through hospital follow up- up to 1 year', 'description': "Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.", 'eventGroups': [{'id': 'EG000', 'title': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.\n\nKarius Test: Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections', 'otherNumAtRisk': 36, 'deathsNumAtRisk': 36, 'otherNumAffected': 0, 'seriousNumAtRisk': 36, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants With a Pathogen Identified by the Initial Karius Test (IP1) and Standard Culture Methods', 'denoms': [{'units': 'Participants', 'counts': [{'value': '36', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Pediatric Musculoskeletal Infections', 'description': 'Children 6 months to 18 years of age admitted to Riley Hospital for Children (Indianapolis, IN), from July 2019 to May 2022. Potential study participants were identified by daily screening of the pediatric infectious diseases and hospitalist patient censuses, and approached for enrollment if there was a strong clinical suspicion of MSKI as evidenced by fever, musculoskeletal pain (e.g. tenderness to palpation of a joint/bone, or refusal to bear weight); and elevated C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)'}], 'classes': [{'title': 'Children with Positive Culture (blood or surgical)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '36', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '23', 'groupId': 'OG000'}]}]}, {'title': 'Children with a positive Karius Test (IP1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '33', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '26', 'groupId': 'OG000'}]}]}, {'title': 'Positive agreement between culture and Karius Test (both tests identified the same organism)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '15', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Inpatient Sample 1 (IP1) - Within 48 hours of admission', 'description': 'We evaluated the total number of participants that had a pathogen identified by the initial (IP1) Karius Test ("positive Karius Test").\n\nWe 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".\n\nWe also evaluated at the number of participants who had negative cultures, but had a positive Karius Test.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': '36 children had a culture obtained (either blood or surgical or both) 33 children had a Karius Test available for analysis (1 sample failed quality control and 2 participants did not have an initial inpatient Karius Test sample drawn) 23 children had a positive culture, however, 1 participant with a positive culture had a Karius sample that failed quality control, leaving 22 available for positive agreement analysis'}, {'type': 'PRIMARY', 'title': 'Number of Participants With a Pathogen Identified by the Karius Test (at Time Point IP2) and Standard Culture Methods', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.\n\nKarius Test: Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections'}], 'classes': [{'categories': [{'title': 'Karius Test positive agreement with culture (blood or surgical)', 'measurements': [{'value': '10', 'groupId': 'OG000'}]}, {'title': 'Karius test discordant with culture (any)', 'measurements': [{'value': '3', 'groupId': 'OG000'}]}, {'title': 'Karius test negative', 'measurements': [{'value': '5', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Inpatient Sample 2 (IP2) - Within 48 hours of the initial sample', 'description': '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).\n\nWe compared the results of the Karius Test to those with a positive culture (gold standard) for each participant.\n\nKarius Test results that matched cultures results (same genus and species) were considered "positive agreement".\n\nKarius 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"', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': '23 children had a positive culture, however, 5 participant with a positive culture did not have an IP2 Karius sample drawn, leaving 18 available for positive agreement analysis'}, {'type': 'SECONDARY', 'title': 'Microbial Cell Free DNA Level (cfDNA) in Molecules Per Microliter (MPM)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.\n\nKarius Test: Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections'}], 'classes': [{'title': 'Severe Infection', 'categories': [{'measurements': [{'value': '408', 'groupId': 'OG000', 'lowerLimit': '358', 'upperLimit': '49185'}]}]}, {'title': 'Non-Severe Infection', 'categories': [{'measurements': [{'value': '322', 'groupId': 'OG000', 'lowerLimit': '92', 'upperLimit': '1357'}]}]}], 'analyses': [{'pValue': '0.36', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEDIAN', 'timeFrame': 'From hospital admission to hospital discharge, up to 3 months', 'description': '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).\n\nOnly those with a positive agreement between initial Karius Test (IP1) and culture were analyzed (n=15).\n\nMann-Whitney U was used to compare median microbial cfDNA between those with non-severe vs. severe MSKI.', 'unitOfMeasure': 'MPM', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Patients with a positive agreement between the Karius Test and cultures'}, {'type': 'SECONDARY', 'title': 'Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.\n\nKarius Test: Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections'}], 'classes': [{'title': 'MPM vs. CRP', 'categories': [{'measurements': [{'value': '0.43', 'groupId': 'OG000'}]}]}, {'title': 'MPM vs. ESR', 'categories': [{'measurements': [{'value': '0.36', 'groupId': 'OG000'}]}]}, {'title': 'MPM vs. WBC', 'categories': [{'measurements': [{'value': '0.33', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Inpatient Sample 1 (IP1) - Within 48 hours of admission', 'description': "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.\n\nSpearman's correlation was used to compare the MPM value to the CRP, ESR and WBC", 'unitOfMeasure': "Spearman's correlation coefficient", 'reportingStatus': 'POSTED', 'populationDescription': 'Patients with a positive agreement between Karius Test and culture who had a Karius Test, CRP, ESR and WBC obtained at time point IP1'}, {'type': 'SECONDARY', 'title': 'Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.\n\nKarius Test: Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections'}], 'classes': [{'categories': [{'measurements': [{'value': '0.79', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Inpatient Sample 2 (IP2) - Within 48 hours of the admission sample', 'description': "We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).\n\nSpearman's correlation was used to compare the MPM value to the CRP", 'unitOfMeasure': "Spearman's correlation coefficient", 'reportingStatus': 'POSTED', 'populationDescription': 'Patients with a positive agreement between Karius Test and culture who had both a Karius Test and CRP obtained at time point IP2'}, {'type': 'SECONDARY', 'title': 'Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Timepoint IP3', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.\n\nKarius Test: Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections'}], 'classes': [{'categories': [{'measurements': [{'value': '1.0', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Inpatient Sample 3 (IP3) - Within 48 hours of the second inpatient sample', 'description': "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.\n\nSpearman's correlation was used to compare the MPM value to the CRP", 'unitOfMeasure': "Spearman's correlation coefficient", 'reportingStatus': 'POSTED', 'populationDescription': 'Patients with a positive agreement between Karius Test and culture who had both a Karius Test and CRP obtained at timepoint IP3'}, {'type': 'SECONDARY', 'title': 'Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point IP4', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.\n\nKarius Test: Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'comment': 'Only 2 participants with positive agreement between the Karius Test and culture had a sample drawn at time point IP4. Analysis requires at least 3 participants.', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Inpatient Sample 4 (IP4) - Within 48 hours of the third inpatient sample', 'description': 'We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).', 'unitOfMeasure': "Spearman's correlation coefficient", 'reportingStatus': 'POSTED', 'populationDescription': 'Patients with a positive agreement between Karius Test and culture who had both a Karius Test and CRP obtained at timepoint IP4'}, {'type': 'SECONDARY', 'title': 'Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.\n\nKarius Test: Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'comment': 'Only 1 participant with a positive agreement between the Karius Test and culture had an OP1 drawn. Analysis could not be done with only 1 participant', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Outpatient Sample 1 (OP1) - 1-2 weeks after hospital discharge', 'description': 'We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).', 'unitOfMeasure': "Spearman's correlation coefficient", 'reportingStatus': 'POSTED', 'populationDescription': 'Participants with a Karius Test and CRP drawn at time point OP1'}, {'type': 'SECONDARY', 'title': 'Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.\n\nKarius Test: Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections'}], 'classes': [{'categories': [{'measurements': [{'value': 'NA', 'comment': 'Only 1 participant with a positive Karius Test drawn at OP2. Analysis could not be done with only 1 participant', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Outpatient Sample 2 (OP2) - 3-6 weeks after hospital discharge', 'description': 'We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).', 'unitOfMeasure': "Spearman's correlation coefficient", 'reportingStatus': 'POSTED', 'populationDescription': 'Participants with a Karius Test and CRP drawn at time point OP2'}, {'type': 'SECONDARY', 'title': 'Microbial Cell Free DNA (cfDNA) in Molecules Per Microliter (MPM) at Time Point OP3', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.\n\nKarius Test: Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections'}], 'timeFrame': 'Outpatient Sample 3 (OP3) - 6-8 weeks after hospital discharge', 'description': 'We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants with a Karius Test and CRP drawn at time point OP3'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Pediatric Musculoskeletal Infections', 'description': 'Children 6 months to 18 years of age admitted to Riley Hospital for Children (Indianapolis, IN), from July 2019 to May 2022. Potential study participants were identified by daily screening of the pediatric infectious diseases and hospitalist patient censuses, and approached for enrollment if there was a strong clinical suspicion of MSKI as evidenced by fever, musculoskeletal pain (e.g. tenderness to palpation of a joint/bone, or refusal to bear weight); and elevated C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '38'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '36'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Refused blood draw', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '36', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Pediatric Musculoskeletal Infections', 'description': 'Children 6 months to 18 years of age admitted to Riley Hospital for Children (Indianapolis, IN), from July 2019 to May 2022. Potential study participants were identified by daily screening of the pediatric infectious diseases and hospitalist patient censuses, and approached for enrollment if there was a strong clinical suspicion of MSKI as evidenced by fever, musculoskeletal pain (e.g. tenderness to palpation of a joint/bone, or refusal to bear weight); and elevated C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000', 'lowerLimit': '4', 'upperLimit': '12'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '11', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '25', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '31', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '28', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Children with musculoskeletal infections'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-10-19', 'size': 580212, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2023-08-02T14:43', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 38}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-09-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-11', 'completionDateStruct': {'date': '2022-06-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-11-11', 'studyFirstSubmitDate': '2019-02-13', 'resultsFirstSubmitDate': '2023-08-02', 'studyFirstSubmitQcDate': '2019-02-15', 'lastUpdatePostDateStruct': {'date': '2023-12-01', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-11-11', 'studyFirstPostDateStruct': {'date': '2019-02-20', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2023-12-01', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-06-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'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', 'description': 'We evaluated the total number of participants that had a pathogen identified by the initial (IP1) Karius Test ("positive Karius Test").\n\nWe 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".\n\nWe also evaluated at the number of participants who had negative cultures, but had a positive Karius Test.'}, {'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', 'description': '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).\n\nWe compared the results of the Karius Test to those with a positive culture (gold standard) for each participant.\n\nKarius Test results that matched cultures results (same genus and species) were considered "positive agreement".\n\nKarius 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"'}], 'secondaryOutcomes': [{'measure': 'Microbial Cell Free DNA Level (cfDNA) in Molecules Per Microliter (MPM)', 'timeFrame': 'From hospital admission to hospital discharge, up to 3 months', 'description': '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).\n\nOnly those with a positive agreement between initial Karius Test (IP1) and culture were analyzed (n=15).\n\nMann-Whitney U was used to compare median microbial cfDNA between those with non-severe vs. severe MSKI.'}, {'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', 'description': "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.\n\nSpearman's correlation was used to compare the MPM value to the CRP, ESR and WBC"}, {'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', 'description': "We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).\n\nSpearman's correlation was used to compare the MPM value to the CRP"}, {'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', 'description': "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.\n\nSpearman's correlation was used to compare the MPM value to the CRP"}, {'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', 'description': 'We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).'}, {'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', 'description': 'We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).'}, {'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', 'description': 'We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).'}, {'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', 'description': 'We evaluated whether cfDNA level (in MPM) correlated with C-reactive protein (a common inflammatory marker used to track inflammation in children with MSKI).'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': True}, 'conditionsModule': {'keywords': ['infection', 'plasma based next generation sequencing', 'blood culture', 'tissue culture', 'joint fluid culture', 'pathogen identification'], 'conditions': ['Musculoskeletal Infection', 'Acute Hematogenous Osteomyelitis', 'Septic Arthritis', 'Osteomyelitis', 'Pyomyositis']}, 'descriptionModule': {'briefSummary': '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).', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '18 Years', 'minimumAge': '6 Months', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. 6 months (to ensure adequate blood volume drawn) to 18 years of age.\n2. 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).\n\nExclusion Criteria:\n\n* Subjects will be excluded if they have clinical evidence suggesting an alternative diagnosis; inability or unwillingness to consent for the study'}, 'identificationModule': {'nctId': 'NCT03846804', 'acronym': 'KDG-002', 'briefTitle': 'Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections', 'organization': {'class': 'OTHER', 'fullName': 'Indiana University'}, 'officialTitle': 'Plasma-Based Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections', 'orgStudyIdInfo': {'id': '1901296571'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Karius Test', 'description': 'Participants will have additional blood drawn for the purposes of analysis with the Karius test.', 'interventionNames': ['Diagnostic Test: Karius Test']}], 'interventions': [{'name': 'Karius Test', 'type': 'DIAGNOSTIC_TEST', 'description': 'Next-generation sequencing of blood and synovial fluid samples for pathogen identification in children with musculoskeletal infections', 'armGroupLabels': ['Karius Test']}]}, 'contactsLocationsModule': {'locations': [{'zip': '46202', 'city': 'Indianapolis', 'state': 'Indiana', 'country': 'United States', 'facility': 'Riley Hospital for Children', 'geoPoint': {'lat': 39.76838, 'lon': -86.15804}}], 'overallOfficials': [{'name': 'Jack G Schneider, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Indiana University School of Medicine - Pediatrics'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Indiana University', 'class': 'OTHER'}, 'collaborators': [{'name': 'Karius, Inc.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor of Clinical Medicine and Clinical Pediatrics', 'investigatorFullName': 'Jack Schneider', 'investigatorAffiliation': 'Indiana University'}}}}