Exploring Novel Diagnostic Tools for Periprosthetic Joint Infection

NCT05582460 | Completed

• 1 other identifier: 2022-2054
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Prosthesis-Related Infections; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee

Outcome Measures

Primary Outcomes (2)

• Fold change of luciferase assay

  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.

  Within 30 days of surgery

• Diagnostic performance of flow cytometric analysis

  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.

  Within 4 hours of surgery

Secondary Outcomes (4)

• Sensitivity of the flow cytometric analysis

  Within 4 hours of surgery

• Specificity of the flow cytometric analysis

  Within 4 hours of surgery

• Positive predictive value of the flow cytometric analysis

  Within 4 hours of surgery

• Negative predictive value of the flow cytometric analysis

  Within 4 hours of surgery

Study Arms (2)

PJI

Patients diagnosed with a PJI based on the EBJIS criteria ('Infection confirmed')

Diagnostic Test: Reporter Gene Assay; Diagnostic Test: Flow Cytometry

No PJI

Patients not diagnosed with a PJI based on EBJIS criteria

Diagnostic Test: Reporter Gene Assay; Diagnostic Test: Flow Cytometry

Interventions

Reporter Gene Assay DIAGNOSTIC_TEST

Transcription factor reporter gene assay using luciferase

No PJI; PJI

Flow Cytometry DIAGNOSTIC_TEST

Flow Cytometry Analysis using the Sysmex UF-4000, analyzing for bacteria, mononuclear and polymorphonuclear cells, and red blood cell and white blood cell count.

No PJI; PJI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients visiting the outpatient clinic of the participating hospitals and planned for elective revision surgery of their THA or TKA.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rijnstate Hospital: lead

Study Sites (1)

Rijnstate Hospital

Arnhem, Gelderland, 6815AD, Netherlands

Location

MeSH Terms

Conditions

Prosthesis-Related Infections

Interventions

Flow Cytometry

Condition Hierarchy (Ancestors)

Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 17, 2022
• Study Start: January 1, 2023
• Primary Completion: May 1, 2024
• Study Completion: July 23, 2025
• Last Updated: August 8, 2025

Record last verified: 2025-08

Locations

NL (1)