AzTrials
AzTrials

Joint InfectionNCT03704766

Alpha-Defensin and Synovial Proteins to Improve Detection of Pediatric Septic Arthritis

A study testing Synovial Alpha-defensin assay, Synovial Neutrophil elastase assay and Synovial lactate assay in people with Joint Infection and Infection of Hip Joint (Disorder), run by Hospital for Special Surgery, New York at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages Up to 17 years
What is being tested?
Synovial Alpha-defensin assay, Synovial Neutrophil elastase assay and Synovial lactate assay
Could I receive a placebo?
No, everyone receives an active treatment
How many people
442 participants
Where
3 sitesUnited States
Study dates
28 Jun 2016to Jan 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

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 Up to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Patients undergoing a procedure unrelated to infection (the procedure may be arthroscopy, or an open or percutaneous bony or soft tissue procedure)

Who cannot join

  • 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

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Grace Wang, BA contact

212-774-2121

wangg@hss.edu

United States3 sites, 3 recruiting
  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30342

    Jack Goldberg, MS, (678) 686-6864, Jack.Goldberg@choa.org

    Tim Schrader, MD, (404) 255-1933

    Recruiting
  • Campbell Clinic

    Collierville, Tennessee, 38017

    Jonathan Rowland, (901) 287-5413, Jonathan.Rowland@lebonheur.org

    Derek Kelly, MD, (901) 759-3100

    Not yet recruiting
  • Hospital for Special Surgery

    New York, New York, 10021

    Grace Wang, BA, 212-774-2121, wangg@hss.edu

    Emily R Dodwell, MD, MPH, 212-606-1451

    Recruiting

Other trials in United States

About this study

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.

Read the detailed description

The purpose of this study is to determine if alpha-defensin and other proteins present in joint fluid may be able to rapidly diagnose bacterial joint infections. Patients with suspected joint infection typically undergo joint aspiration so that tests can be performed to help diagnose joint infection, including gram stain, cell count, and culture. Patients under 18 years old that are undergoing sampling of their joint fluid due to suspicion of infection or inflammation will be enrolled in this multi-center trial. Joint fluid will also be sampled from normative controls made up of patients who are undergoing an unrelated procedure without inflammation or infection. Joint fluid from patients with suspected inflammation/infection and from normative controls will be analysed for presence of alpha-defensin, leukocyte esterase, neutrophil elastase, synovial C-reactive protein, and synovial lactate. The alpha-defensin assay has shown high sensitivity and specificity for joint infection in other studies. Additionally a Staphylococcus spp antigen panel, Candida spp antigen panel, Enterococcus faecalis assay, BACTAlert culture, cell count plus differential, gram stain, and aerobic, anaerobic, and fungal cultures will be done using synovial fluid. A synovial fluid PCR for Kingella kingae will be performed if the patient is under eight years of age. Blood tests will include cell count and differential, erythrocyte sedimentation rate, C-reactive protein, procalcitonin, and D-dimer, as well as relevant inflammatory or rheumatologic marker tests. Results from these tests will be compared to joint fluid culture which the gold standard for diagnosing bacterial infection. The study includes 1 visit per patient, the standard of care visit in which the patient would be undergoing joint aspiration or arthroscopy. Once data has been collected, the sensitivity and specificity will be determined for these experimental tests both individually and in combination.

Being tested
Synovial Alpha-defensin assay, Synovial Neutrophil elastase assay, Synovial lactate assay, Synovial C-reactive Protein (CRP), Synovial Staphylococcus spp antigen panel
Keywords
synovial biomarkers, alpha-defensin, diagnostics, pediatric
Medical subject headings
Arthritis, Infectious

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Synovial Alpha-defensin assayDiagnostic test

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

  • Synovial Neutrophil elastase assayDiagnostic test

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

  • Synovial lactate assayDiagnostic test

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

  • 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.

  • Synovial Staphylococcus spp antigen panelDiagnostic test

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

  • Synovial Candida spp antigen panelDiagnostic test

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

  • Synovial Enterococcus faecalis assayDiagnostic test

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

  • 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.

  • 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.

  • Synovial Gram StainDiagnostic test

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

  • 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.

  • Synovial PCR for Kingella kingaeDiagnostic test

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

  • Serum Cell count + differential (CBC)Diagnostic test

    A blood test performed at the hospital.

  • Serum erythrocyte sedimentation rate (ESR)Diagnostic test

    A blood test performed at the hospital.

  • Serum C-reactive Protein (CRP)Diagnostic test

    A blood test performed at the hospital.

  • Serum D-dimerDiagnostic test

    A blood test performed at the hospital.

  • Serum ProcalcitoninDiagnostic test

    A blood test performed at the hospital.

  • Blood CulturesDiagnostic test

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

  • 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.

Study groups in NCT03704766
Study groupRoleWhat they receive
Inflamed/Infected JointExperimentalPatients undergoing joint aspiration/debridement due to suspicion of septic joint or rheumatologic/inflammatory condition
Receives: Diagnostic Test: Synovial Alpha-defensin assay; Diagnostic Test: Synovial Neutrophil elastase assay; Diagnostic Test: Synovial lactate assay; Diagnostic Test: Synovial C-reactive Protein (CRP); Diagnostic Test: Synovial Staphylococcus spp antigen panel; Diagnostic Test: Synovial Candida spp antigen panel; Diagnostic Test: Synovial Enterococcus faecalis assay; Diagnostic Test: Synovial bacterial culture by BacT/Alert; Diagnostic Test: Synovial Cell count + differential (CBC); Diagnostic Test: Synovial Gram Stain; Diagnostic Test: Synovial Leukocyte Esterase Test Strips; Diagnostic Test: Synovial PCR for Kingella kingae; Diagnostic Test: Serum Cell count + differential (CBC); Diagnostic Test: Serum erythrocyte sedimentation rate (ESR); Diagnostic Test: Serum C-reactive Protein (CRP); Diagnostic Test: Serum D-dimer; Diagnostic Test: Serum Procalcitonin; Diagnostic Test: Blood Cultures; Diagnostic 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 ControlActive comparatorPatient undergoing procedure unrelated to infection/inflammation
Receives: Diagnostic Test: Synovial Alpha-defensin assay; Diagnostic Test: Synovial Neutrophil elastase assay; Diagnostic Test: Synovial lactate assay; Diagnostic Test: Synovial C-reactive Protein (CRP); Diagnostic Test: Synovial Staphylococcus spp antigen panel; Diagnostic Test: Synovial Candida spp antigen panel; Diagnostic Test: Synovial Enterococcus faecalis assay; Diagnostic Test: Synovial bacterial culture by BacT/Alert; Diagnostic Test: Synovial Cell count + differential (CBC); Diagnostic Test: Synovial Gram Stain; Diagnostic Test: Synovial Leukocyte Esterase Test Strips; Diagnostic Test: Synovial PCR for Kingella kingae; Diagnostic Test: Serum Cell count + differential (CBC); Diagnostic Test: Serum erythrocyte sedimentation rate (ESR); Diagnostic Test: Serum C-reactive Protein (CRP); Diagnostic Test: Serum D-dimer; Diagnostic Test: Serum Procalcitonin; Diagnostic Test: Blood Cultures; Diagnostic Test: Optional blood testing per standard of care (ASO, anti-strep, ANA, anti-DS-DNA, HLA-B27, RF, Lyme and other inflammatory/ rheumatologic markers )

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Interim analysis at 2 years of study recruitment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2018
  2. Study start28 Jun 2016
  3. Primary completionNov 2026 (estimated)
  4. Study completionJan 2027 (estimated)

Resources

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
Non-randomised
Intervention model
Parallel groups
Model description
Participants are assigned as either cases of infection/inflammation, or normative controls, and receive the same diagnostic testing for the duration of the study.
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
442 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03704766
Sponsor's protocol ID
2015-947
Status last verified
Jun 2024
First submitted
8 May 2018
Last updated
29 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: 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.

Publications

  • 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.

    PubMed 25256621
  • 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.

    PubMed 697948
  • 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.

    PubMed 21843213
  • 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.

    PubMed 25626524
  • 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.

    PubMed 24496757
  • 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.

    PubMed 25187582
  • 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.

    PubMed 25631170
  • 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.

    PubMed 25672257
  • 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.

    PubMed 18812907
  • 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.

    PubMed 2997278
  • 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.

    PubMed 27216361
  • 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.

    PubMed 25740029
  • 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.

    PubMed 23826894
  • 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.

    PubMed 25869063
  • 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.

    PubMed 24843434

Questions about this trial

What is this clinical trial studying?

A study testing Synovial Alpha-defensin assay, Synovial Neutrophil elastase assay and Synovial lactate assay in people with Joint Infection and Infection of Hip Joint (Disorder), run by Hospital for Special Surgery, New York at 3 sites 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 1 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Grace Wang, BA (212-774-2121, wangg@hss.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Sensitivity and specificity of experimental tests (time frame: Interim analysis at 2 years of study recruitment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03704766, which also lists 18 linked publications.

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 29 Jul 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in