MedPath

Exploring Novel Diagnostic Tools for Periprosthetic Joint Infection

Active, not recruiting
Conditions
Arthroplasty, Replacement, Knee
Arthroplasty, Replacement, Hip
Prosthesis-Related Infections
Interventions
Diagnostic Test: Reporter Gene Assay
Diagnostic Test: Flow Cytometry
Registration Number
NCT05582460
Lead Sponsor
Rijnstate Hospital
Brief Summary

Joint replacement is a valuable surgical intervention that improves quality of life, provides pain relief, and restores function of patients. However, some patients need revision surgery due to failure of the implant, with periprosthetic joint infection (PJI) remaining a rare but serious complication following total hip (THA) and knee (TKA) arthroplasty. Diagnosing PJI is a major challenge as no diagnostic test with absolute accuracy exists. The diagnosis is based on a combination of clinical findings, laboratory results from peripheral blood and synovial fluid, microbiological culture, histological evaluation of periprosthetic tissue, and intraoperative findings. However, the preoperative diagnosis can be inconclusive and operative criteria are required for the definitive diagnosis. Therefore, novel diagnosing tools for identification of PJI are necessary.

A recent study using a gene reporter assay, identified biomarkers in synovial fluid that define joint states in patients with osteoarthritis.However, no previous studies have investigated cellular signaling in synovial fluid of patients with PJI. With this study we want to explore the potential of a reporter gene assay of synovial fluid in patients with PJI and without PJI of their TKA and THA.

Also, flow cytometry analysis of biological fluids has recently received increased attention as a potentially valuable method in diagnosing infections. For example, the method is already used to analyze urine samples for urinary tract infections. Recently, researchers have now also used this method to screen for the presence of bacteria. The most important limitation of flow cytometry analysis of synovial fluids for bacteria to date is that it is unclear as to which bacteria count value - the cutoff value - represent patients with PJI and which represent patients without PJI. With this study we want to explore the potential of flow cytometry analysis of synovial fluid in categorizing patients with PJI and without PJI.

Our primary objective is to explore the value of synovial fluid analysis using a reporter gene assay and flow cytometry in the detection of a periprosthetic joint infection.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
60
Inclusion Criteria
  • All patients planned for elective THA or TKA revision surgery with revision of one or more fixed components will be eligible to participate in this study.
Exclusion Criteria
  • are planned for a revision of single mobile parts only;
  • have received intravenous and/or oral antibiotics within 2 weeks before the diagnostic workup and/or surgery;
  • are unable to provide their consent for use of their human tissues for medical research.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
No PJIReporter Gene AssayPatients not diagnosed with a PJI based on EBJIS criteria
No PJIFlow CytometryPatients not diagnosed with a PJI based on EBJIS criteria
PJIFlow CytometryPatients diagnosed with a PJI based on the EBJIS criteria ('Infection confirmed')
PJIReporter Gene AssayPatients diagnosed with a PJI based on the EBJIS criteria ('Infection confirmed')
Primary Outcome Measures
NameTimeMethod
Diagnostic performance of flow cytometric analysisWithin 4 hours of surgery

Diagnostic performance of the flow cytometry analysis of synovial fluid by determining difference in results between two groups using ROC curve analysis.

If a cut-off point has been determined, sensitivity (SN), specificity (SP), negative (NPV) and positive predictive value (PPV) can be calculated.

Fold change of luciferase assayWithin 30 days of surgery

Diagnostic performance of the reporter gene assay of synovial fluid by calculating fold change data from the reporter gene measurements.

A luciferase assay will be performed using the collected synovial fluid and the amount of luciferase activity will be measured by luminometer and expressed in relative light units (RLU). A background control (e.g., medium or buffer alone) will be used to evaluate raw RLU values that will be subtracted from all the sample values for better accuracy. The data for the reporter assay will be expressed using an equation to determine normalized fold change in activity between the two groups.

Secondary Outcome Measures
NameTimeMethod
Sensitivity of the flow cytometric analysisWithin 4 hours of surgery
Negative predictive value of the flow cytometric analysisWithin 4 hours of surgery
Positive predictive value of the flow cytometric analysisWithin 4 hours of surgery
Specificity of the flow cytometric analysisWithin 4 hours of surgery

Trial Locations

Locations (1)

Rijnstate Hospital

🇳🇱

Arnhem, Gelderland, Netherlands

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