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

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест Synovial Alpha-defensin assay
  One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
• Диагностический тест Synovial Neutrophil elastase assay
  One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
• Диагностический тест Synovial lactate assay
  Synovial Fluid (joint fluid) will be sent out to CD Diagnostics for this test.
• Диагностический тест Synovial C-reactive Protein (CRP)
  One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
• Диагностический тест Synovial Staphylococcus spp antigen panel
  One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
• Диагностический тест Synovial Candida spp antigen panel
  One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
• Диагностический тест Synovial Enterococcus faecalis assay
  One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
• Диагностический тест Synovial bacterial culture by BacT/Alert
  The synovial fluid (joint fluid) sent to CD Diagnostics for testing will also be cultured to see if any organisms grow.
• Диагностический тест Synovial Cell count + differential (CBC)
  One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
• Диагностический тест Synovial Gram Stain
  This will be performed by CD Diagnostics if any organisms are present in the synovial fluid.

Первичные конечные точки

• Sensitivity and specificity of experimental tests [Срок оценки: Interim analysis at 2 years of study recruitment]

Критерии участия

Inclusion Criteria- Septic Cases and Inflamed, Non-Septic Comparators:

• 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

Inclusion Criteria- Normative Controls:

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

Exclusion Criteria- All Participants:

• 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

Exclusion Criteria- Normative Controls:

• A history of recent infection (within the past 3 months)
• Received antibiotics in the past 7 days

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Диагностика

Центры проведения

США · 3 центра

• Children's Healthcare of Atlanta — Atlanta
• Hospital for Special Surgery — New York
• Campbell Clinic — Collierville

Публикации

• 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 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 25672257

Идентификаторы

NCT: NCT03704766 · 2015-947

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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