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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	N/A - 17 Years
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03704766
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Hospital for Special Surgery, New York
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Emily R Dodwell, MD, MPH
Principal Investigator Affiliation	The Hospital for Special Surgery
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Joint Infection, Infection of Hip Joint (Disorder), Infection of Shoulder Joint, Septic Arthritis
Study Website:	View Trial Website

Additional Details

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.

Arms & Interventions

Arms

Experimental: Inflamed/Infected Joint

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

Active Comparator: Normative Control

Patient undergoing procedure unrelated to infection/inflammation