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

• ClinicalTrials.gov Identifier: NCT03694925
• Recruitment Status: Completed
• First Posted: October 3, 2018
• Results First Posted: December 17, 2020
• Last Update Posted: December 17, 2020
• Sponsor: The Cleveland Clinic
• Information provided by (Responsible Party): Carlos Higuera-Rueda, The Cleveland Clinic

Study Description

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.

Condition or disease	Intervention/treatment
Prosthetic Joint Infection	Diagnostic Test: Calprotectin test

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 156 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Diagnostic Utility of a Novel Point-of-Care Test of Calprotectin for Revision Total
• Actual Study Start Date: October 29, 2018
• Actual Primary Completion Date: January 7, 2020
• Actual Study Completion Date: March 4, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Primary total knee arthroplasty; Primary TKA patients included in the study, to provide a baseline level for calprotectin.	Diagnostic Test: Calprotectin 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.	Diagnostic Test: Calprotectin 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.	Diagnostic Test: Calprotectin test; Calprotectin will be measured both by ELISA and point of care test.

Outcome Measures

Primary Outcome Measures :

1. Calprotectin POC [ Time Frame: Day of surgery ]
   lateral flow point of care test

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Three groups:

Primary total knee arthroplasty Aseptic revision total knee arthroplasty Septic revision total knee arthroplasty

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)

Contacts and Locations

Locations

United States, Florida

Cleveland Clinic Florida

Weston, Florida, United States, 33331

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

The Cleveland Clinic

Investigators

• Principal Investigator: Carlos Higuera, MD; The Cleveland Clinic

  Study Documents (Full-Text)

Documents provided by Carlos Higuera-Rueda, The Cleveland Clinic:

Study Protocol and Statistical Analysis Plan  [PDF] March 17, 2020

More Information

• Responsible Party: Carlos Higuera-Rueda, Chairman, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT03694925
• Other Study ID Numbers: 18-882
• First Posted: October 3, 2018
• Results First Posted: December 17, 2020
• Last Update Posted: December 17, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: The only group we will be sharing data with is the company (Lyfstone) which is funding the research.

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