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. (PJI MAP/DEF)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Periprosthetic Joint Infection; Suspected Periprosthetic Joint Infection; Prosthetic Joint Failure of Unclear Etiology
• Intervention / Treatment: Diagnostic test: Comprehensive Diagnostic Work-up for Suspected Chronic Periprosthetic Joint Infection

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.

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • University Hospital Ghent (UZ Gent), Belgium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients
• Presence of a joint prosthesis.
• Clinical suspicion of chronic periprosthetic joint infection.
• Scheduled for diagnostic arthroscopy and/or open surgical evaluation as part of standard care.
• Written informed consent provided.

Exclusion Criteria:

• Acute postoperative infections.
• Inability or refusal to provide informed consent.
• Insufficient clinical data or samples for diagnostic evaluation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Single arm study with observational and diagnostic puproses; Participants receive diagnostic investigations that are clinically indicated as part of routine care for suspected chronic periprosthetic joint infection. No additional diagnostic or therapeutic procedures are mandated by the study protocol.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy	Diagnostic accuracy (sensitivity, specificity) of individual and combined diagnostic modalities for chronic PJI, using a comprehensive multidisciplinary reference standard.	From the start of standard of care treatment during phase 1, 2, or 3 until 1 year after collection date.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Refining the diagnosis or treatment of the donor based on new diagnostic data	Based on reports from qPCR Rapid Screening and Next Generation Comprehensive DNA Sequencing for 'unknown microorganisms, including bacteria and fungi' we aim to examin: identification and localisation of the causative microorganisms - the correlation of synovial fluid, tissue cultures and ultrasound - additional diagnostic value of minimally invasive arthroscopy and nuclear imaging - the impact of combined diagnostic strategies in fase 1, 2 and 3.	From the start of standard of care treatment during phase 1, 2, or 3 until 1 year after collection date.

Collaborators and Investigators

• Sponsor: University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2018
• Primary Completion (Actual): December 18, 2024
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Diagnostic accuracy; Arthroscopy; Histopathology; Next-generation sequencing (NGS); Nuclear imaging; Periprosthetic joint infection; Chronic PJI; Synovial fluid analysis; Microbiological cultures; Unified PJI definition
• Other Study ID Numbers: BC-08886; FWOOPR2023006203 (Other Grant/Funding Number: Foundation of scientific research ( Federal Belgium))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No