New Molecular Approaches for Diagnosis of Prosthetic Joint Infection

October 31, 2024 updated by: I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

Innovative Molecular Approaches for the Diagnosis of Prosthetic Joint Infections

The goals of this observational study are:

  1. to evaluate the concordance between traditional method (culture) and genomic method in diagnosing prosthetic joint infections;
  2. to define an algorithm for laboratory diagnosis of prosthetic joint infections, which could be easily applied in our hospital setting;
  3. to test different DNA extraction protocols to obtain high yields of microbial nucleic acids from infected human tissue samples.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Subjects A total of 70 patients from the Department of Reconstructive Surgery and Osteoarticular Infections (CRIO) and the Hip Units of IRCCS Ospedale Galeazzi -Sant'Ambrogio for suspected infection of their prosthesis will be enrolled in the study. Each sample will be analized with both traditional culture and Next Generation Sequencing (NGS).

On the basis of culture results patients will be divided into 3 groups.

Sample collection for Molecular analysis Sampling from peri-prosthetic tissue with macroscopic signs of infection will be taken from the synovial membrane, bone-prosthetic interface and intramedullary canals. Synovial fluid will be sterilely collected in DNAse and RNAse free containers for NGS analysis before performing the arthrotomy. Sterile swabs and pads will be used to collect samples from interface between tissue and bone implant and from intramedullary canal for NGS analysis. Bone tissue will be collected with new sterile instrumentation. Samples will be frozen within 2 hours from collection at -80°C until .

Sample collection for culture Sample collection of periprosthetic tissues and implant will be performed during the surgery after the proper exposure of the affected site. Synovial fluid will be collected in sterile screw cap tubes. Periprosthetic tissues and implant will be collected in sterile containers by using new sterile instrumentation. All samples will be sent to the Laboratory within 2 hours from collection. Samples after treatment with 0.1% (w:v) Dithiothreitol to dislodge bacteria from biofilm will be cultured on agar plates and broth for aerobes and anaerobes for 15 days. Microbial identification will be performed by biochemical assays.

A further tissue sample, collected in a separate sterile screw cap tube, will be used for host DNA removal to isolate microbial DNA, for shotgun NGS. Samples will be treated with saponin and/or different commercial kits for microbial DNA extraction. The dsDNA will be quantified with a Qubit fluorometer, and its purity will be determined with a nanodrop spectophotometer.

Synovial fluid analysis Synovial fluid for leukocyte count and differential will be collected in EthylenDiaminoTetraAcetic Acid (EDTA) containing tubes and analyzed by means of a Sysmex XN haematological analyser.

Determination of synovial protein, glucose, C-Reactive Protein (CRP) and leukocyte esterase will be performed on synovial fluid collected in clot activator containing tubes. Measurement of proteins, glucose and CRP will be carried out on Atellica CH and IM analyser (Siemens) while leukocyte esterase was determined by used of strips for urinalysis.

Molecular analysis 70 samples will be sent to a specialized laboratory which will perform nucleic acid extraction from biological specimen types using tailored proprietary techniques that include concentrating cellular material, mechanical lysis, and removing organic inhibitors and human host DNA. Every specimen will be processed with a positive and negative extraction control to assure quality.

At the end of the study any residual biological material will be destroyed

Statistical methodology Sample size The sample size has been calculated considering as the primary outcome the agreement of the innovative molecular method and the traditional culture of periprostethic tissue and synovial fluid in defining a patients as positive or negative for prosthetic joint infections . Based on investigators experience, the proportion of patients, undergoing revision surgery for knee and hip implant failure in IRCCS Ospedale Galeazzi Sant'Ambrogio with diagnosis of prosthetic joint infection based on cultural exam is of 45%. Considering a margin of error of 15%, an alpha = 0.05 and power = 80%, the number of patients to be tested is 70.

Analysis methodology Categorical data will be described as absolute and relative frequencies, while continuous data will be described as mean and 95%-confidence interval, if normally distributed, or as median and interquartile range, in case of non-normal distribution. Normal distribution will be assessed by the Shapiro-Wilk test.

Differences in proportion will be evaluated by Fisher's exact test or Chi-squared test; continuous variable comparison among the three groups will be performed using One-Way Analysis Of Variance (ANOVA) test for normally distributed data or with Kruskal-Wallis test, in case of non-normal distribution.

Agreement between molecular methods with traditional culture of periprostethic tissue and synovial fluid will be tested using Choen's kappa.

Sensitivity and specificity of each assay will be also assessed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milano, Italy, 20157
        • IRCCS Ospedale Galeazzi-Sant'Ambrogio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

A total of 70 patients from the Department of Reconstructive Surgery and Osteoarticular Infections (CRIO) and the Hip Units of IRCCS Ospedale Galeazzi -Sant'Ambrogio for suspected infection of their prosthesis will be enrolled in the study.

Description

Inclusion Criteria:

  • Age >18 years
  • Males and females
  • Patients with a clinical indication for knee and hip revision surgery admitted at IRCCS Ospedale Galeazzi - Sant'Ambrogio

Exclusion Criteria:

  • Insufficient amount of periprosthetic tissue and synovial fluid collected
  • Patients unable to sign the Informed Consent
  • Pregnancy and breast feeding with declaration of patient
  • Age <18 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Group A
Patients with diagnosis of infection confirmed by culture results
Group B
Patients with diagnosis of prosthetic joint infection according to criteria of the MusculoSkeletal Infection Society (MSIS) but with negative culture
Group C
Patients with no evidence of prosthetic joint infection according to criteria of MusculoSkeletal Infection Society (MSIS) (negative controls)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Concordance between analytical methods
Time Frame: 24 months

Concordance between methods will be analyzed by

  1. Patient categorization (Infected/not infected)
  2. Microorganisms identification
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Definition of an algorithm for laboratory diagnosis of prosthetic joint infections
Time Frame: 36 months
Results will be used for development of an algorithm for definition of workflow for diagnosis of prostehtic joint infections
36 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Comparison of different protocols for microbial DNA extraction
Time Frame: 18 months
Different commercial kit for microbial DNA extraction will be assessed in order to define an accurate and efficient protocol for microbial DNA extraction from periprosthetic tissues
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 29, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2024

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 1, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 1, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Merian
  • L2071 (Other Identifier: IRCCS Ospedale Galeazzi-Sant'Ambrogio)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Only data useful for publication will be made avalilable

IPD Sharing Time Frame

IPD will be avalable form the end of the study

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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