NCT03704766

Brief Summary

Differentiating between septic arthritis and other causes of joint inflammation in pediatric patients is challenging and of the utmost importance because septic arthritis requires surgical debridement as part of the treatment regimen. The current gold standard to diagnose septic arthritis in children is a positive synovial fluid culture; however, joint cultures may take several days to return. If a bacterial infection is present, it requires immediate surgical intervention in order to prevent lasting articular cartilage damage. Frequently surgeons must decide whether to surgically debride a joint before culture results are available. There is no single lab test or clinical feature that reliably indicates bacterial infection over other causes of joint inflammation. The alpha-defensin assay has shown high sensitivity and specificity for joint infection in other studies.The purpose of this study is to determine the sensitivity and specificity of several synovial biomarkers for diagnosing pediatric septic arthritis.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
442

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jun 2016

Longer than P75 for not_applicable

Geographic Reach
1 country

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 28, 2016

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

May 8, 2018

Completed
5 months until next milestone

First Posted

Study publicly available on registry

October 15, 2018

Completed
7.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2026

Completed
Last Updated

June 22, 2025

Status Verified

June 1, 2024

Enrollment Period

9.8 years

First QC Date

May 8, 2018

Last Update Submit

June 17, 2025

Conditions

Joint InfectionInfection of Hip Joint (Disorder)Infection of Shoulder JointSeptic Arthritis

Keywords

synovial biomarkersalpha-defensindiagnosticspediatric

Outcome Measures

Primary Outcomes (1)

  • Sensitivity and specificity of experimental tests

    Sensitivity and specificity have been selected as these are standard outcome tests when determining the utility of a diagnostic test.

    Interim analysis at 2 years of study recruitment

Study Arms (2)

Inflamed/Infected Joint

EXPERIMENTAL

Patients undergoing joint aspiration/debridement due to suspicion of septic joint or rheumatologic/inflammatory condition

Diagnostic Test: Synovial Alpha-defensin assayDiagnostic Test: Synovial Neutrophil elastase assayDiagnostic Test: Synovial lactate assayDiagnostic Test: Synovial C-reactive Protein (CRP)Diagnostic Test: Synovial Staphylococcus spp antigen panelDiagnostic Test: Synovial Candida spp antigen panelDiagnostic Test: Synovial Enterococcus faecalis assayDiagnostic Test: Synovial bacterial culture by BacT/AlertDiagnostic Test: Synovial Cell count + differential (CBC)Diagnostic Test: Synovial Gram StainDiagnostic Test: Synovial Leukocyte Esterase Test StripsDiagnostic Test: Synovial PCR for Kingella kingaeDiagnostic Test: Serum Cell count + differential (CBC)Diagnostic Test: Serum erythrocyte sedimentation rate (ESR)Diagnostic Test: Serum C-reactive Protein (CRP)Diagnostic Test: Serum D-dimerDiagnostic Test: Serum ProcalcitoninDiagnostic Test: Blood CulturesDiagnostic Test: Optional blood testing per standard of care (ASO, anti-strep, ANA, anti-DS-DNA, HLA-B27, RF, Lyme and other inflammatory/ rheumatologic markers )

Normative Control

ACTIVE COMPARATOR

Patient undergoing procedure unrelated to infection/inflammation

Diagnostic Test: Synovial Alpha-defensin assayDiagnostic Test: Synovial Neutrophil elastase assayDiagnostic Test: Synovial lactate assayDiagnostic Test: Synovial C-reactive Protein (CRP)Diagnostic Test: Synovial Staphylococcus spp antigen panelDiagnostic Test: Synovial Candida spp antigen panelDiagnostic Test: Synovial Enterococcus faecalis assayDiagnostic Test: Synovial bacterial culture by BacT/AlertDiagnostic Test: Synovial Cell count + differential (CBC)Diagnostic Test: Synovial Gram StainDiagnostic Test: Synovial Leukocyte Esterase Test StripsDiagnostic Test: Synovial PCR for Kingella kingaeDiagnostic Test: Serum Cell count + differential (CBC)Diagnostic Test: Serum erythrocyte sedimentation rate (ESR)Diagnostic Test: Serum C-reactive Protein (CRP)Diagnostic Test: Serum D-dimerDiagnostic Test: Serum ProcalcitoninDiagnostic Test: Blood CulturesDiagnostic Test: Optional blood testing per standard of care (ASO, anti-strep, ANA, anti-DS-DNA, HLA-B27, RF, Lyme and other inflammatory/ rheumatologic markers )

Interventions

Synovial Alpha-defensin assayDIAGNOSTIC_TEST

One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.

Inflamed/Infected JointNormative Control
Synovial Neutrophil elastase assayDIAGNOSTIC_TEST

One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.

Inflamed/Infected JointNormative Control
Synovial lactate assayDIAGNOSTIC_TEST

Synovial Fluid (joint fluid) will be sent out to CD Diagnostics for this test.

Inflamed/Infected JointNormative Control
Synovial C-reactive Protein (CRP)DIAGNOSTIC_TEST

One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.

Inflamed/Infected JointNormative Control
Synovial Staphylococcus spp antigen panelDIAGNOSTIC_TEST

One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.

Inflamed/Infected JointNormative Control
Synovial Candida spp antigen panelDIAGNOSTIC_TEST

One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.

Inflamed/Infected JointNormative Control
Synovial Enterococcus faecalis assayDIAGNOSTIC_TEST

One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.

Inflamed/Infected JointNormative Control
Synovial bacterial culture by BacT/AlertDIAGNOSTIC_TEST

The synovial fluid (joint fluid) sent to CD Diagnostics for testing will also be cultured to see if any organisms grow.

Inflamed/Infected JointNormative Control
Synovial Cell count + differential (CBC)DIAGNOSTIC_TEST

One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.

Inflamed/Infected JointNormative Control
Synovial Gram StainDIAGNOSTIC_TEST

This will be performed by CD Diagnostics if any organisms are present in the synovial fluid.

Inflamed/Infected JointNormative Control
Synovial Leukocyte Esterase Test StripsDIAGNOSTIC_TEST

These test strips will be tested at the hospital where the patient is being seen, a few drops of synovial fluid will be used on the strip.

Inflamed/Infected JointNormative Control
Synovial PCR for Kingella kingaeDIAGNOSTIC_TEST

In participants \< 8 years old, a sample of synovial fluid will be tested for Kingella kingae using PCR.

Inflamed/Infected JointNormative Control
Serum Cell count + differential (CBC)DIAGNOSTIC_TEST

A blood test performed at the hospital.

Inflamed/Infected JointNormative Control
Serum erythrocyte sedimentation rate (ESR)DIAGNOSTIC_TEST

A blood test performed at the hospital.

Inflamed/Infected JointNormative Control
Serum C-reactive Protein (CRP)DIAGNOSTIC_TEST

A blood test performed at the hospital.

Inflamed/Infected JointNormative Control
Serum D-dimerDIAGNOSTIC_TEST

A blood test performed at the hospital.

Inflamed/Infected JointNormative Control
Serum ProcalcitoninDIAGNOSTIC_TEST

A blood test performed at the hospital.

Inflamed/Infected JointNormative Control
Blood CulturesDIAGNOSTIC_TEST

Blood will be cultured at the hospital to see if any organisms grow.

Inflamed/Infected JointNormative Control
Optional blood testing per standard of care (ASO, anti-strep, ANA, anti-DS-DNA, HLA-B27, RF, Lyme and other inflammatory/ rheumatologic markers )DIAGNOSTIC_TEST

In patients with suspected inflammation/infection, there are other blood tests which may be standard of care and used for diagnosis.

Inflamed/Infected JointNormative Control

Eligibility Criteria

AgeUp to 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Synovial fluid is obtained to assess for infection or inflammatory/rheumatologic disease (all medium and large joints will be included: hip, knee, ankle, shoulder, subtalar, elbow, and wrist joints)
  • Patients with recent antibiotic exposure are eligible to participate but will be analyzed separately
  • Patients undergoing a procedure unrelated to infection (the procedure may be arthroscopy, or an open or percutaneous bony or soft tissue procedure)

You may not qualify if:

  • Family declines to participate/consent
  • Patients with a major joint trauma (such as a documented ligament tear or fracture) within the past 8 weeks are not eligible to have that joint aspirated, but could have another joint aspirated
  • A history of recent infection (within the past 3 months)
  • Received antibiotics in the past 7 days

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30342, United States

RECRUITING

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

Campbell Clinic

Collierville, Tennessee, 38017, United States

NOT YET RECRUITING

Related Publications (18)

  • Bingham J, Clarke H, Spangehl M, Schwartz A, Beauchamp C, Goldberg B. The alpha defensin-1 biomarker assay can be used to evaluate the potentially infected total joint arthroplasty. Clin Orthop Relat Res. 2014 Dec;472(12):4006-9. doi: 10.1007/s11999-014-3900-7. Epub 2014 Sep 26.

    PMID: 25256621BACKGROUND

  • Brook I, Reza MJ, Bricknell KS, Bluestone R, Finegold SM. Synovial fluid lactic acid. A diagnostic aid in septic arthritis. Arthritis Rheum. 1978 Sep-Oct;21(7):774-9. doi: 10.1002/art.1780210706.

    PMID: 697948BACKGROUND

  • Carpenter CR, Schuur JD, Everett WW, Pines JM. Evidence-based diagnostics: adult septic arthritis. Acad Emerg Med. 2011 Aug;18(8):781-96. doi: 10.1111/j.1553-2712.2011.01121.x.

    PMID: 21843213BACKGROUND

  • Colvin OC, Kransdorf MJ, Roberts CC, Chivers FS, Lorans R, Beauchamp CP, Schwartz AJ. Leukocyte esterase analysis in the diagnosis of joint infection: can we make a diagnosis using a simple urine dipstick? Skeletal Radiol. 2015 May;44(5):673-7. doi: 10.1007/s00256-015-2097-5. Epub 2015 Jan 29.

    PMID: 25626524BACKGROUND

  • Cunningham G, Seghrouchni K, Ruffieux E, Vaudaux P, Gayet-Ageron A, Cherkaoui A, Godinho E, Lew D, Hoffmeyer P, Uckay I. Gram and acridine orange staining for diagnosis of septic arthritis in different patient populations. Int Orthop. 2014 Jun;38(6):1283-90. doi: 10.1007/s00264-014-2284-3. Epub 2014 Feb 5.

    PMID: 24496757BACKGROUND

  • Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Parvizi J. Combined measurement of synovial fluid alpha-Defensin and C-reactive protein levels: highly accurate for diagnosing periprosthetic joint infection. J Bone Joint Surg Am. 2014 Sep 3;96(17):1439-45. doi: 10.2106/JBJS.M.01316.

    PMID: 25187582BACKGROUND

  • Deirmengian C, Kardos K, Kilmartin P, Gulati S, Citrano P, Booth RE Jr. The Alpha-defensin Test for Periprosthetic Joint Infection Responds to a Wide Spectrum of Organisms. Clin Orthop Relat Res. 2015 Jul;473(7):2229-35. doi: 10.1007/s11999-015-4152-x.

    PMID: 25631170BACKGROUND

  • Frangiamore SJ, Saleh A, Grosso MJ, Kovac MF, Higuera CA, Iannotti JP, Ricchetti ET. alpha-Defensin as a predictor of periprosthetic shoulder infection. J Shoulder Elbow Surg. 2015 Jul;24(7):1021-7. doi: 10.1016/j.jse.2014.12.021. Epub 2015 Feb 8.

    PMID: 25672257BACKGROUND

  • Gafur OA, Copley LA, Hollmig ST, Browne RH, Thornton LA, Crawford SE. The impact of the current epidemiology of pediatric musculoskeletal infection on evaluation and treatment guidelines. J Pediatr Orthop. 2008 Oct-Nov;28(7):777-85. doi: 10.1097/BPO.0b013e318186eb4b.

    PMID: 18812907BACKGROUND

  • Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427-35. doi: 10.1172/JCI112120.

    PMID: 2997278BACKGROUND

  • Hatakeyama Y, Miura H, Sato A, Onodera Y, Sato N, Shimizu D, Kumazawa Y, Sanada H, Hirano H, Terada Y. Neutrophil elastase in amniotic fluid as a predictor of preterm birth after emergent cervical cerclage. Acta Obstet Gynecol Scand. 2016 Oct;95(10):1136-42. doi: 10.1111/aogs.12928. Epub 2016 Jun 17.

    PMID: 27216361BACKGROUND

  • Heyworth BE, Shore BJ, Donohue KS, Miller PE, Kocher MS, Glotzbecker MP. Management of pediatric patients with synovial fluid white blood-cell counts of 25,000 to 75,000 cells/mm(3) after aspiration of the hip. J Bone Joint Surg Am. 2015 Mar 4;97(5):389-95. doi: 10.2106/JBJS.N.00443.

    PMID: 25740029BACKGROUND

  • Maharajan K, Patro DK, Menon J, Hariharan AP, Parija SC, Poduval M, Thimmaiah S. Serum Procalcitonin is a sensitive and specific marker in the diagnosis of septic arthritis and acute osteomyelitis. J Orthop Surg Res. 2013 Jul 4;8:19. doi: 10.1186/1749-799X-8-19.

    PMID: 23826894BACKGROUND

  • Potter BK. From Bench to Bedside: Alpha-defensing--The Biggest Thing in Joint Replacement Infections Since Prophylactic Antibiotics? Clin Orthop Relat Res. 2015 Oct;473(10):3105-7. doi: 10.1007/s11999-015-4297-7. Epub 2015 Apr 14. No abstract available.

    PMID: 25869063BACKGROUND

  • Nakamura A, Osonoi T, Terauchi Y. Relationship between urinary sodium excretion and pioglitazone-induced edema. J Diabetes Investig. 2010 Oct 19;1(5):208-11. doi: 10.1111/j.2040-1124.2010.00046.x.

    PMID: 24843434BACKGROUND

  • Riise OR, Kirkhus E, Handeland KS, Flato B, Reiseter T, Cvancarova M, Nakstad B, Wathne KO. Childhood osteomyelitis-incidence and differentiation from other acute onset musculoskeletal features in a population-based study. BMC Pediatr. 2008 Oct 20;8:45. doi: 10.1186/1471-2431-8-45.

    PMID: 18937840BACKGROUND

  • Wang C, Wang Q, Li R, Duan JY, Wang CB. Synovial Fluid C-reactive Protein as a Diagnostic Marker for Periprosthetic Joint Infection: A Systematic Review and Meta-analysis. Chin Med J (Engl). 2016 Aug 20;129(16):1987-93. doi: 10.4103/0366-6999.187857.

    PMID: 27503025BACKGROUND

  • Wyatt MC, Beswick AD, Kunutsor SK, Wilson MJ, Whitehouse MR, Blom AW. The Alpha-Defensin Immunoassay and Leukocyte Esterase Colorimetric Strip Test for the Diagnosis of Periprosthetic Infection: A Systematic Review and Meta-Analysis. J Bone Joint Surg Am. 2016 Jun 15;98(12):992-1000. doi: 10.2106/JBJS.15.01142.

    PMID: 27307359BACKGROUND

Related Links

MeSH Terms

Conditions

Arthritis, Infectious

Interventions

Blood Cell CountBlood Culture

Condition Hierarchy (Ancestors)

InfectionsArthritisJoint DiseasesMusculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Cell CountCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisHematologic TestsInvestigative TechniquesCell Physiological PhenomenaBlood Physiological PhenomenaCirculatory and Respiratory Physiological PhenomenaMicrobiological Techniques

Study Officials

  • Emily R Dodwell, MD, MPH

    The Hospital for Special Surgery

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Grace Wang, BA

CONTACT

212-774-2121wangg@hss.edu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Masking Details
For patients with inflamed joints, the medical team will be blind to the results of the alpha-defensin assay and other experimental tests for a period of 2 weeks, after which results may be divulged to the clinical team at their request. As such, the results will not influence the physician/surgeons' decision for acute treatment of the patient, as the decision to treat suspected septic arthritis is typically made within 24 hours, and the final diagnosis is made within 2 weeks (pending culture results). As the testing of the leukocyte esterase strips will occur in the operating room, the surgeon will not be blinded to these results. A blinded team member will read the pictures of all of the leukocyte test strip results at once, after they have all been collected. The patient will be made aware of results at the physician/surgeon's discretion. For normative controls, the results of experimental testing will not be divulged to the clinical team or to the patient.
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Model Details: Participants are assigned as either cases of infection/inflammation, or normative controls, and receive the same diagnostic testing for the duration of the study.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 8, 2018

First Posted

October 15, 2018

Study Start

June 28, 2016

Primary Completion

May 1, 2026

Study Completion

May 1, 2026

Last Updated

June 22, 2025

Record last verified: 2024-06

Data Sharing

IPD Sharing
Will not share

Collaborating sites will share de-identified patient data with the primary site, the Hospital for Special Surgery. The Hospital for Special Surgery, will incorporate de-identified aggregated data into a separate de-identified aggregated data sat to be provided to all study sites, but individual participant data will not be shared with all sites.

Locations

US(3)