Clinical trial NCT04056780: Integrated Microfluidic Systems for Diagnosis of Periprosthetic Joint Infection
Official title: Diagnosis of Periprosthetic Joint Infection With Synovial Fluid Biomarkers Through Integrated Microfluidic Systems
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Prosthetic Joint Infection
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2019-08-14
Enrollment: 150
Sex: ALL
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Given the lack of published data regarding the application of 2nd ICM criteria, we will not perform a power analysis for sample size calculation before the study. All consecutive patients undergoing revision total joint arthroplasty (hips and knees) will be eligible for recruitment.

Brief summary: Diagnosing periprosthetic joint infection (PJI) remains a major clinical challenge. The diagnosis of PJI is based on a composition of clinical judgment, serologic test from peripheral blood, synovial fluid cytology and biomarkers, radiography, microbiology, histopathologic evaluation of periprosthetic tissue, and intraoperative findings. The importance of PJI diagnosis give the subsequent treatment options, like the removal of prosthesis, debridement and prosthesis retention and the time of reimplantation.

Currently, The Second International Consensus Meeting (ICM) has announced its criteria for the diagnosis of PJI. The preoperative diagnosis includes serologic tests (C-reactive protein, D-dimer, and erythrocyte sedimentation rate) and synovial fluid biomarkers (white blood cell and differential, leukocyte esterase and ⍺-defensin). The intraoperative diagnosis includes a single positive culture, positive histology, and positive intraoperative purulence. However, some of the markers used in the 2018 ICM criteria, such as ⍺-defensin, leukocyte esterase, and synovial fluid C-reactive protein, are not available in every hospital and cannot be immediately available to clinicians in decision making.

The microfluidic technologies have made a notable impact on the evolution of diagnostic tools by providing a rapid and cost-effective platform for the application of immunoassay techniques. The microfluidic system integrates the complex processing steps of the laboratory protocols into a single chip through logical integration and optimization of processes. Chang Gung Memorial Hospital and National Tsing Hua University have conducted preliminary research to confirm the feasibility of their microfluidic systems.

Therefore, the project will develop a "microfluidic biomarker detection chip" to detect the concentrations three important biomarkers for PJI, including ⍺-defensin, leukocyte esterase and C-reactive protein in synovial fluids. This will be a three-year project. In the 1st year, 50 patients who will be scheduled to undergo unilateral revision total joint arthroplasty (RTJA) will be collected with the synovial fluid and tested on a laboratory platform. In the 2nd year, based on laboratory results, 50 patients undergoing RTJAs will be recruited to develop a microfluidic chip system, and their on-chip performance will be fine-tuned and optimized. In the 3rd year, 50 patients undergoing RTJA will be collected, and the verification of the microfluidic system will be realized. This system will be validated in PJIs cohorts in the first stage of debridement and implant removal, in the interim period, and the second stage of reimplantation. It is expected that biomarker detection chip will improve medical distress and bring important information to clinical decision-making.


Eligibility criteria: Inclusion Criteria:

1. Revision total knee arthroplasty
2. Revision total hip arthroplasty
3. Sufficiently annotated clinical and laboratory data for classification by the 2018 ICM criteria for PJI
4. Sufficient synovial fluid for study methods.

Exclusion Criteria:

1. Inadequate synovial fluid for analysis
2. Adverse local tissue reaction (ALTR)
3. Crystalline deposition arthropathy
4. Inflammatory arthropathy flare

Primary outcomes:
measure: The value of synovial fluid human ⍺-defensin 1-3 (HNP1-3)
timeFrame: Post-operative period after collect per 40 cases (usually within 180-365 days following surgery)
measure: The value of leukocyte esterase (LE)
timeFrame: Immediate post-operative period (usually within 1-2 days following surgery)
measure: The value of synovial C-reactive protein (CRP)
timeFrame: Immediate post-operative period (usually within 1-2 days following surgery)
Secondary outcomes:
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
Study officials:
References: