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

NCT ID: NCT03694925

Last Updated: 2020-12-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 156 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-10-29
• Study Completion Date: 2020-03-04

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.

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. In a subgroup analysis for patients with chronic PJI, a NPV of 97% was observed. 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.

Conditions

Prosthetic Joint Infection

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Primary total knee arthroplasty

Primary TKA patients included in the study, to provide a baseline level for calprotectin.

Calprotectin test

Intervention Type: DIAGNOSTIC_TEST

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

Aseptic revision total knee arthroplasty

Aseptic revision TKA patients included in the study. These are patients who are not considered infected according to Musculoskeletal Infection Society criteria for infection.

Calprotectin test

Intervention Type: DIAGNOSTIC_TEST

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

Revision septic total knee arthroplasty

Septic revision TKA patients included in the study. These are patients who are considered infected according to Musculoskeletal Infection Society criteria for infection.

Calprotectin test

Intervention Type: DIAGNOSTIC_TEST

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

Interventions

Calprotectin test

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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Carlos Higuera-Rueda

Chairman

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carlos Higuera, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic Florida

Weston, Florida, United States

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

18-882

Identifier Type: -

Identifier Source: org_study_id