Diagnostic Utility of a Novel Point-of-Care Test of Calprotectin for Revision Total Knee Arthroplasty

Sponsor:

Collaborators:

Information provided by (Responsible Party):

Carlos Higuera-Rueda，The Cleveland Clinic

Tracking Information

First Submitted Date ^ICMJE

October 2, 2018

First Posted Date ^ICMJE

October 3, 2018

Last Update Posted Date

October 3, 2018

Actual Study Start Date ^ICMJE

November 2018

Estimated Primary Completion Date

December 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Calprotectin POC[ Time Frame: Day of surgery ]

Point of care test

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Calprotectin ELISA[ Time Frame: Day of surgery ]
ELISA analysis

Descriptive Information

Brief Title ^ICMJE

Diagnostic Utility of a Novel Point-of-Care Test of Calprotectin for Revision Total Knee Arthroplasty

Official Title ^ICMJE

Diagnostic Utility of a Novel Point-of-Care Test of Calprotectin for Revision Total

Brief Summary

The purpose of this study is to investigate whether there are quantifiable differences in the level of calprotectin in the synovial fluid that allow separation of different modes of joint implant failure (e.g. infected, aseptic loosening). A subset of primary TKA patients (with history of OA) will be included as a baseline.

Detailed Description

Calprotectin is a biomarker closely associated with leucocytes in general, and is present in high volumes in neutrophil cells. Calprotectin is also produced by infiltrating monocytes and macrophages, where calprotectin is released upon phagocytosis. In neutrophils, calprotectin is stored intracellularly and are released upon activation of the cell. The determination of number of neutrophils and proportion of neutrophils out of total number of inflammatory cells is a diagnostic strategy commonly used in diagnosis of infection. Upon encounter with a pathogen, neutrophils have several strategies to fight infections , and produce high-levels of calprotectin. Activation of neutrophils, and release of calprotectin, can be for any reason causing activation of the complement system and aseptic Inflammatory responses. Moreover, Calprotectin is a danger associated molecular patterns (DAMP) signal influencing the inflammatory responses. The level of activated neutrophils in PJI provide basis of the presence of calprotectin in the synovial fluid of PJI patients, and thus, for calprotectin as a potential biomarker for PJI. Calprotectin-levels in the synovial fluid do not merely reflect the level of leucocytes and neutrophils present in the synovial fluid, but levels are correlated to the WBC content. Calprotectin is likely to reflect the number of activated cells and surpass the diagnostic accuracy of total WBC counts and neutrophil percentage for PJI diagnosis. Wouthuyzen-Bakker et al. demonstrated that a level of calprotectin of 50 mg/L in the synovial fluid has very good diagnostic accuracy for PJI, supported by area under the curve values of more than 0.9. This break point produced a negative predictive value (NPV) of 95% for all 42 patients in the study. In a subgroup analysis for patients with chronic PJI, a NPV of 97% was observed[19]. The excellent NPV may assist in the orthopaedic clinic to rule out the presence of infection and consider diagnostic alternatives for aseptic loosening and pain revision of the joint patient. A rapid and accurate distinction between these two causes is important as PJI and aseptic loosening are managed differently with regards to surgical Intervention and followup. Point of Care Test diagnostics by lateral flow devices provides reliable test results within minutes of sample collection. Currently, Calprotectin can be detected by such lateral flow devices (developed by Orthogenics, Tromsø, Norway). The speed and ease of use of this test allows for diagnosis at patient's bed side. These tests can be applied in the physician's office, operating room, an ambulance, the home, the field, or in the hospital. As the results are timely they allow rapid diagnostic and identifies treatment alternatives for the patient. This technology empowers clinicians to make decisions at the "point-of-care" and can have significant impact on health care delivery and ability to address challenges of health disparities. However, it is important to validate the diagnostic utility of calprotectin POC in a diverse set of patients undergoing revision arthroplasty.

Study Type ^ICMJE

Observational

Study Phase

Study Design ^ICMJE

Allocation:
Intervention Model:
Intervention Model Description:
Masking: Observational
Masking Description:
Primary Purpose:

Condition ^ICMJE

Intervention ^ICMJE

Diagnostic Test: Calprotectin test
Calprotectin will be measured both by ELISA and point of care test.

Study Arms

: Primary total knee arthroplasty
There will be n=30 primary TKA patients included in the study, to provide a baseline level for calprotectin.
: Aseptic revision total knee arthroplasty
There will be n=50 aseptic revision TKA patients included in the study. These are patients who are not considered infected according to Musculoskeletal Infection Society criteria for infection.
: Revision total knee arthroplasty
There will be n=70 septic revision TKA patients included in the study. These are patients who are considered infected according to Musculoskeletal Infection Society criteria for infection.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

150

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

May 2020

Estimated Primary Completion Date

December 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria: Subject is ≥18 years of age. Patient with a diagnosis of OA (for primary TKA only) Subject has had no recent injections or surgeries of the joint (within past 6 weeks). Subject has or will have all of the medical tests required to allow MSIS classification. Subject signs informed consent form. Exclusion Criteria: Subjects with a diagnostic synovial fluid specimen collection within the past 7 days. Results are not available for medical tests required to perform MSIS classification. Sample was obtained via lavage Quantity not sufficient (at least 1 ml required).

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

Carlos Higuera-Rueda，The Cleveland Clinic

Study Sponsor ^ICMJE

The Cleveland Clinic

Collaborators ^ICMJE

Investigators ^ICMJE

PRS Account

The Cleveland Clinic

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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