NCT07494630

Joint Endoprostheses Can Succesfully Treat Disabling Osteoarthritis. However, Infection is an Important Cause of Failure. Adequate Diagnostics Remains Challenging. Combining Advanced Imaging With Next-generation Sequencing of Samples Obtained Endoscopically Should Aid in Mapping and Characterizing.

The Unhappy Patient With a Painful Joint Endoprosthesis: Mapping a Periprosthetic Joint Infection and Analysis of Themicrobiome/Biofilm

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 174 (actual)
• Sponsor: University Hospital, Ghent · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This prospective observational diagnostic study aims to improve the accuracy and timeliness of diagnosing chronic periprosthetic joint infection (PJI). By systematically integrating clinical history, serological markers, synovial fluid analysis, microbiological cultures, next-generation sequencing (NGS), histopathology, minimally invasive arthroscopic sampling, open surgical sampling, sonication, and nuclear imaging, the study evaluates which diagnostic factors and combinations thereof most reliably identify the presence, extent, location, and causative microorganism(s) of PJI. The ultimate objective is to provide evidence-based recommendations to refine and optimize the current unified PJI diagnostic definition.

Detailed description

The ability to perform additional DNA analysis on the residual material from these samples (which would otherwise be discarded) offers the prospect of obtaining a more accurate picture of the microbiome and the biofilm present on the prosthetic components. This is the aim of the project. Based on criteria for suspected infection (Musculoskeletal Infection Society and the European Society for Bone and Joint Infections), selected patients undergo standard testing via analysis of blood, synovial fluid, tissue, and bone (marrow) samples, as well as imaging such as X-rays, MRI, and nuclear scans. If, based on this (Phase 1), the diagnosis and nature of an infection are clear, the diagnostic procedure of arthroscopy combined with periprosthetic synovial tissue, bone, and bone marrow biopsies (Phase 2) and proceed directly to open surgery, in which part or all of the prosthesis is replaced in one or two sessions (Phase 3), and synovial fluid, tissue, bone, and bone marrow samples are also taken. All samples obtained during Phase 1, 2, or 3 are subjected to standard microbiological and pathological testing; however, the residual material is now also subjected to genetic analysis of bacterial/fungal DNA. The patient's human DNA is not tested. Samples are obtained using separate instruments to prevent cross-contamination. Synovial fluid (1 to 10 mL), synovial tissue (2 to 6 mm³), and bone (bone marrow) (2 to 6 mL) harvested in and around the prosthetic components are collected and stored in sterile containers for microbiological examination and in sterile containers containing formaldehyde for pathological examination. Each container is labeled with patient identification and the location of the harvest (e.g., lower leg, lateral side). A bag containing 6 to 8 labeled containers is transported to the Microbiology lab. A similar bag is sent to the Pathology lab. There is always excess fluid, tissue, bone, or bone marrow material (1 to 2 ml or mm³ per site). This material is normally discarded. For this research project, it is collected, but unlike the microbiological and pathological samples, these containers are only coded (e.g., SEPTORT001 (the number stands for patient one) synovial fluid, synovium 1, synovium 2, (biofilm in) acetabulum, (biofilm in) femur greater trochanter, (biofilm) femur mid-diaphysis, (biofilm on) tip of stem in a hip prosthesis). At the end of the session, the containers are collected in a small plastic bag. This bag is placed in a larger plastic bag along with a MicroGenDx form. This form contains the following information: SEPTORT and patient number, age, sex, right or left side, joint (hip, knee, shoulder prosthesis…), the date of collection, the working diagnosis (periprosthetic joint infection), checkbox for orthopedic examination, checkbox for desired analysis (qPCR Rapid Screening and NGS), as well as the principal investigator's signature. At the end of the surgical session, he personally brings this to the HIRUZ BioBank for handover to be stored in a -80°C freezer. Once about five bags have been collected over a period of a few weeks, an international courier picks up a cardboard box containing these bags. The Medical Research box (no dry ice required) is sealed by a lab technician at the HIRUZ Biobank. The box is usually picked up on a Tuesday afternoon and arrives at the laboratory in Texas the following morning on Wednesday (local time). Depending on the normal clinical workload, the research samples are processed for genetic analysis of the microbiome either on the same day or at a later time after storage. The U.S. laboratory does not receive any data that could identify the patient. The data from the genetic analysis results are encrypted and transmitted electronically in a secure format to the principal investigator at UZ Gent. Only the principal investigator and Professor David Creytens are authorized to access this database. Both are responsible for continuous quality control of the security system, thereby preventing unauthorized access to the data, in accordance with Good Clinical Practice guidelines. This research should enable us to confirm or rule out whether an underlying prosthetic infection is indeed the cause of the patient's symptoms, but it can also help determine the topography of the infection-specifically, whether it is diffuse or concentrated in a specific prosthetic component-as well as the composition of the microbiome and biofilm.

Conditions

• Chronic Periprosthetic Joint Infection
• Suspected Periprosthetic Joint Infection
• Prosthetic Joint Failure of Unclear Etiology

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Comprehensive Diagnostic Work-up for Suspected Chronic Periprosthetic Joint Infection	Participants undergo a comprehensive, multimodal diagnostic work-up for suspected chronic periprosthetic joint infection as part of standard clinical care. This diagnostic assessment may include clinical history evaluation, serological testing, synovial fluid analysis, microbiological cultures, next-generation sequencing (NGS), histopathological examination, nuclear imaging, minimally invasive arthroscopic sampling, open surgical sampling, and sonication of explanted components where applicable. No experimental treatment is administered. All diagnostic procedures are performed according to routine clinical practice. The study evaluates the diagnostic performance, concordance, and added value of individual and combined diagnostic modalities for the detection, characterization, and localization of periprosthetic joint infection.

Timeline

• Start date: 2018-09-18
• Primary completion: 2024-12-18
• Completion: 2027-12-31
• First posted: 2026-03-27
• Last updated: 2026-03-27

Locations

1 site across 1 country: Belgium