Diagnosis and Bacterial Identification of Periprosthetic Joint Infection With Microbial-ID (MID)

The primary objective of this study is to demonstrate the validity of the Microbial- ID test to aid in diagnosis of periprosthetic joint infection (PJI) in terms of sensitivity and specificity.

Study Overview

• Status: Enrolling by invitation
• Conditions: Periprosthetic Joint Infection; PJI
• Intervention / Treatment: Diagnostic test: Microbial ID test

Detailed Description

In the diagnosis of periprosthetic joint infection (PJI) there is no golden standard test. Multiple definitions for the diagnosis of PJI exist, such as the European Bone and Joint Infection Society (EBJIS)1, Musculoskeletal Infection Society (MSIS)2, and the Infectious Diseases Society of America (IDSA)3. One of the criteria that defines PJI is that there are at least two positive periprosthetic cultures with phenotypically identical organisms. Although these two positive bacterial cultures can certainly be considered proof of PJI, many other criteria are also used, such as a sinus tract, white blood count (WBC), elevated C-reactive protein and/or erythrocyte sedimentation rate (ESR), elevated percentage of neutrophils, and positive alpha defensin. Even when all these criteria are negative, a PJI cannot be excluded. Zimmer Biomet developed the Synovasure® Microbial-ID test that enables early and faster identification of microbial species through detection of microbial antigens responsible for infection.

This is an international multicenter, non-randomized, prospective, non-intervention clinical investigation.The primary objective of this study is to demonstrate the validity of the Microbial-ID test to aid in diagnosis of PJI in terms of sensitivity and specificity. The study population is adult patients with a potentially infected joint implant, who will undergo an articular puncture and/or surgery with harvesting of synovial fluid. In addition to the standard of care procedure for patients with a suspected PJI, the MID-test will be performed using the residual synovial fluid. Individual test results of the MID-test are not reported back to the participating sites in order to not interfere with the sites' standard of care approach.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients do not benefit from participating in this study. A separate diagnostic tool will run in parallel but this procedure will not interfere with the patient's current path of diagnostic work up nor will it have an effect on their treatment plan. The results will help the investigators to get more insight in the reliability of the MID-test to detect microbial antigens responsible for the PJI. There are no known disadvantages for the patients taking part in this research.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Charité Universitätsmedizin Berlin
• Netherlands
  • Utrecht, Netherlands, 3584CX
    • UMC Utrecht
• Portugal
  • Porto, Portugal
    • Hospitalar do Porto,
• Slovenia
  • Valdoltra, Slovenia
    • Valdoltra Orthopeadic Hospital,
• Spain
  • Barcelona, Spain
    • Hospital Clinic Barcelona
• Switzerland
  • Basel, Switzerland
    • Universitätsspital Basel,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with a potentially infected joint implant, who will undergo an articular puncture and/or surgery with harvesting of synovial fluid.

Description

Inclusion Criteria:

• Patient has complaints (pain, stiffness) about the prosthetic joint And has clinical features for joint infection at physical examination (swelling, redness, warm, sinus tract) AND has an elevated serum CRP (>10 mg/L)
• Patient is scheduled for a puncture AND/OR surgery, with harvesting of synovial fluid
• Patient ≥ 18 years of age
• Patient is competent, able, and willing to provide written informed consent

Exclusion Criteria:

• Treatment with antibiotics ≤2 weeks prior to puncture and/or surgery;
• Other obvious reason(s) for implant dysfunction, such as: fracture, an implant breakage, a malposition, and/or a tumour.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients suspected of PJI; Adult patients, both male and female, scheduled for a puncture or surgery of their prosthetic joint due to suspected PJI.

Diagnostic test: Microbial ID test; In addition to the standard of care procedure for patients suspected for a periprosthetic joint infection, the MID-test will be performed using the residual synovial fluid. Individual test results of the MID-test are not reported back to the participating sites in order to not interfere with the sites' standard of care approach.; Other Names: Synovasure® Microbial Identification Test; Synovasure® Microbial ID P. acnes Test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of the MID-test	Sensitivity of the MID-test based upon the number of subjects with a positive MID-test AND ≥1 positive microbiology culture(s) for the same bacterial species (true positives) and the number of subjects with a negative MID-test AND ≥1 positive microbiology culture(s) for one of the four bacterial species the MID-test is testing for (false negatives).	after 3 weeks
Specificity of the MID-test	Specificity of the MID-test based upon the number of subjects with a negative MIDtest AND only negative microbiology cultures (true negatives) and the number subjects with a positive MID-test AND only negative microbiology cultures (false positives).	after 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of MID-test and the MB culture(s) regarding the time-to-result.	Comparison of the time-to-result (elapsing hours between harvesting and test result) of the MID-test and the microbiology culture(s).	after 3 weeks
Rate of identification of bacterial species by the MID-test and the corresponding MB culture(s).	Rate of identification of bacterial species by the MID-test and the corresponding microbiology culture(s).	after 3 weeks
Proportion of agreement between the MID-test and the diagnosis of PJI according to the EBJIS definition.	Proportion of agreement between the MID-test and the diagnosis of PJI according to the EBJIS definition as assessed by a blinded investigator.	after 3 weeks
Rate of "false positives" in the reported low-grade PJIs at ≥1-year follow-up.	Rate of "false positives" (MID test (+) and MB culture (-) at F0) in the reported low-grade (MB (-) and clinical signs (+)) PJIs at ≥1-year follow-up.	after 1 year

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Zimmer Biomet
• Investigators: Principal Investigator: Harrie Weinans, Prof, MD, H.H.Weinans@umcutrecht.nl

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2022
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: April 1, 2022
• First Submitted That Met QC Criteria: April 1, 2022
• First Posted (Actual): April 11, 2022

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Periprosthetic joint infection; Microbial-ID test
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Arthritis; Infections; Communicable Diseases; Arthritis, Infectious
• Other Study ID Numbers: 22-072

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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