Clinical trial NCT03704766: Alpha-Defensin and Synovial Proteins to Improve Detection of Pediatric Septic Arthritis
Official title: Alpha-Defensin and Synovial Proteins to Improve Detection of Pediatric Septic Arthritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Joint Infection
Infection of Hip Joint (Disorder)
Infection of Shoulder Joint
Septic Arthritis
Keywords: synovial biomarkers
alpha-defensin
diagnostics
pediatric
Lead sponsor: Hospital for Special Surgery, New York
Sponsor class: OTHER
Collaborators: name: Pediatric Orthopaedic Society of North America
name: Children's Healthcare of Atlanta
name: Campbell Clinic
name: CD Diagnostics
First posted: 2018-10-15
Enrollment: 442
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sensitivity and specificity of experimental tests
timeFrame: Interim analysis at 2 years of study recruitment
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Collierville
country: United States
facility: Campbell Clinic
state: Tennessee
Study officials:
affiliation: The Hospital for Special Surgery
name: Emily R Dodwell, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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