Infection of Hip Joint (Disorder), Infection of Shoulder Joint, Joint Infection, Septic Arthritis
Conditions
Keywords
synovial biomarkers, alpha-defensin, diagnostics, pediatric
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.
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.
Interventions
DIAGNOSTIC_TESTSynovial Alpha-defensin assay
One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
DIAGNOSTIC_TESTSynovial Neutrophil elastase assay
One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
DIAGNOSTIC_TESTSynovial lactate assay
Synovial Fluid (joint fluid) will be sent out to CD Diagnostics for this test.
DIAGNOSTIC_TESTSynovial C-reactive Protein (CRP)
One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
DIAGNOSTIC_TESTSynovial Staphylococcus spp antigen panel
One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
DIAGNOSTIC_TESTSynovial Candida spp antigen panel
One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
DIAGNOSTIC_TESTSynovial Enterococcus faecalis assay
One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
DIAGNOSTIC_TESTSynovial 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.
DIAGNOSTIC_TESTSynovial Cell count + differential (CBC)
One of the synovial fluid (joint fluid) tests that will be performed by the outside lab, CD Diagnostics.
DIAGNOSTIC_TESTSynovial Gram Stain
This will be performed by CD Diagnostics if any organisms are present in the synovial fluid.
DIAGNOSTIC_TESTSynovial Leukocyte Esterase Test Strips
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.
DIAGNOSTIC_TESTSynovial PCR for Kingella kingae
In participants \< 8 years old, a sample of synovial fluid will be tested for Kingella kingae using PCR.
DIAGNOSTIC_TESTSerum Cell count + differential (CBC)
A blood test performed at the hospital.
DIAGNOSTIC_TESTSerum erythrocyte sedimentation rate (ESR)
A blood test performed at the hospital.
DIAGNOSTIC_TESTSerum C-reactive Protein (CRP)
A blood test performed at the hospital.
DIAGNOSTIC_TESTSerum D-dimer
A blood test performed at the hospital.
DIAGNOSTIC_TESTSerum Procalcitonin
A blood test performed at the hospital.
DIAGNOSTIC_TESTBlood Cultures
Blood will be cultured at the hospital to see if any organisms grow.
DIAGNOSTIC_TESTOptional blood testing per standard of care (ASO, anti-strep, ANA, anti-DS-DNA, HLA-B27, RF, Lyme and other inflammatory/ rheumatologic markers )
In patients with suspected inflammation/infection, there are other blood tests which may be standard of care and used for diagnosis.
Sponsors
Hospital for Special Surgery, New York
Pediatric Orthopaedic Society of North America
Children's Healthcare of Atlanta
Campbell Clinic
CD Diagnostics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Caregiver)
Masking description
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.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity and specificity of experimental tests | Interim analysis at 2 years of study recruitment | Sensitivity and specificity have been selected as these are standard outcome tests when determining the utility of a diagnostic test. |
Countries
United States
Contacts
CONTACTGrace Wang, BA
PRINCIPAL_INVESTIGATOREmily R Dodwell, MD, MPH
The Hospital for Special Surgery
Outcome results
None listed