Trial Outcomes & Findings for Diagnostic Utility of a Novel Point-of-Care Test of Calprotectin for Revision Total Knee Arthroplasty (NCT NCT03694925)
NCT ID: NCT03694925
Last Updated: 2020-12-17
Results Overview
lateral flow point of care test
Recruitment status
COMPLETED
Target enrollment
156 participants
Primary outcome timeframe
Day of surgery
Results posted on
2020-12-17
Participant Flow
Participant milestones
| Measure |
Primary Total Knee Arthroplasty
Primary TKA patients included in the study, to provide a baseline level for calprotectin.
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.
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.
Calprotectin test: Calprotectin will be measured both by ELISA and point of care test.
|
|---|---|---|---|
|
Overall Study
STARTED
|
30
|
73
|
53
|
|
Overall Study
COMPLETED
|
30
|
70
|
53
|
|
Overall Study
NOT COMPLETED
|
0
|
3
|
0
|
Reasons for withdrawal
| Measure |
Primary Total Knee Arthroplasty
Primary TKA patients included in the study, to provide a baseline level for calprotectin.
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.
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.
Calprotectin test: Calprotectin will be measured both by ELISA and point of care test.
|
|---|---|---|---|
|
Overall Study
Inadequate laboratory testing
|
0
|
3
|
0
|
Baseline Characteristics
ESR was not collected for primary TKA as it is not standard of care ESR was not ordered by the physician for 2 septic cases
Baseline characteristics by cohort
| Measure |
Primary Total Knee Arthroplasty
n=30 Participants
Primary TKA patients included in the study, to provide a baseline level for calprotectin.
Calprotectin test: Calprotectin will be measured both by ELISA and point of care test.
|
Aseptic Revision Total Knee Arthroplasty
n=70 Participants
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: Calprotectin will be measured both by ELISA and point of care test.
|
Revision Septic Total Knee Arthroplasty
n=53 Participants
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: Calprotectin will be measured both by ELISA and point of care test.
|
Total
n=153 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
67.2 Years
STANDARD_DEVIATION 9.8 • n=30 Participants
|
65.4 Years
STANDARD_DEVIATION 10.6 • n=70 Participants
|
68.8 Years
STANDARD_DEVIATION 10.2 • n=53 Participants
|
66.9 Years
STANDARD_DEVIATION 10.4 • n=153 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=30 Participants
|
40 Participants
n=70 Participants
|
26 Participants
n=53 Participants
|
83 Participants
n=153 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=30 Participants
|
30 Participants
n=70 Participants
|
27 Participants
n=53 Participants
|
70 Participants
n=153 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=30 Participants
|
0 Participants
n=70 Participants
|
0 Participants
n=53 Participants
|
0 Participants
n=153 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=30 Participants
|
0 Participants
n=70 Participants
|
0 Participants
n=53 Participants
|
0 Participants
n=153 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=30 Participants
|
0 Participants
n=70 Participants
|
0 Participants
n=53 Participants
|
0 Participants
n=153 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=30 Participants
|
11 Participants
n=70 Participants
|
6 Participants
n=53 Participants
|
22 Participants
n=153 Participants
|
|
Race (NIH/OMB)
White
|
25 Participants
n=30 Participants
|
58 Participants
n=70 Participants
|
47 Participants
n=53 Participants
|
130 Participants
n=153 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=30 Participants
|
1 Participants
n=70 Participants
|
0 Participants
n=53 Participants
|
1 Participants
n=153 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=30 Participants
|
0 Participants
n=70 Participants
|
0 Participants
n=53 Participants
|
0 Participants
n=153 Participants
|
|
BMI
|
34.2 kg/m^2
STANDARD_DEVIATION 5.9 • n=30 Participants
|
32.0 kg/m^2
STANDARD_DEVIATION 6.2 • n=70 Participants
|
34.2 kg/m^2
STANDARD_DEVIATION 9.7 • n=53 Participants
|
33.2 kg/m^2
STANDARD_DEVIATION 7.6 • n=153 Participants
|
|
Charlson Comorbidity Index
|
3.4 units on a scale from 0 to 27
STANDARD_DEVIATION 2.0 • n=30 Participants
|
3.4 units on a scale from 0 to 27
STANDARD_DEVIATION 1.9 • n=70 Participants
|
4.6 units on a scale from 0 to 27
STANDARD_DEVIATION 2.5 • n=53 Participants
|
3.8 units on a scale from 0 to 27
STANDARD_DEVIATION 2.2 • n=153 Participants
|
|
Erythrocyte Sedimentation Rate
|
—
|
14 mm/hr
STANDARD_DEVIATION 11 • n=70 Participants • ESR was not collected for primary TKA as it is not standard of care ESR was not ordered by the physician for 2 septic cases
|
57 mm/hr
STANDARD_DEVIATION 35 • n=51 Participants • ESR was not collected for primary TKA as it is not standard of care ESR was not ordered by the physician for 2 septic cases
|
33 mm/hr
STANDARD_DEVIATION 32 • n=121 Participants • ESR was not collected for primary TKA as it is not standard of care ESR was not ordered by the physician for 2 septic cases
|
|
C Reactive Protein
|
—
|
0.6 mg/dl
STANDARD_DEVIATION 0.7 • n=70 Participants • CRP was not collected for primary TKA as it is not standard of care CRP was not ordered by the physician for the 1 septic case
|
11.8 mg/dl
STANDARD_DEVIATION 14.6 • n=52 Participants • CRP was not collected for primary TKA as it is not standard of care CRP was not ordered by the physician for the 1 septic case
|
5.4 mg/dl
STANDARD_DEVIATION 11.0 • n=122 Participants • CRP was not collected for primary TKA as it is not standard of care CRP was not ordered by the physician for the 1 septic case
|
|
Synovial WBC Count
|
—
|
735 cells/ micro liter
STANDARD_DEVIATION 856 • n=70 Participants • Synovial WBC was not collected for primary TKA as it is not standard of care Synovial WBC was unable to be run due to insufficient quantity for the 1 septic case
|
57803 cells/ micro liter
STANDARD_DEVIATION 66595 • n=52 Participants • Synovial WBC was not collected for primary TKA as it is not standard of care Synovial WBC was unable to be run due to insufficient quantity for the 1 septic case
|
25059 cells/ micro liter
STANDARD_DEVIATION 51598 • n=122 Participants • Synovial WBC was not collected for primary TKA as it is not standard of care Synovial WBC was unable to be run due to insufficient quantity for the 1 septic case
|
|
Synovial PMN%
|
—
|
21 percentage of cells
STANDARD_DEVIATION 24 • n=70 Participants • Synovial PMN% was not collected for primary TKA as it is not standard of care Synovial PMN% was unable to be run due to insufficient quantity for 2 septic cases
|
89 percentage of cells
STANDARD_DEVIATION 13 • n=51 Participants • Synovial PMN% was not collected for primary TKA as it is not standard of care Synovial PMN% was unable to be run due to insufficient quantity for 2 septic cases
|
50 percentage of cells
STANDARD_DEVIATION 39 • n=121 Participants • Synovial PMN% was not collected for primary TKA as it is not standard of care Synovial PMN% was unable to be run due to insufficient quantity for 2 septic cases
|
|
Current Smoker
|
1 Participants
n=30 Participants
|
5 Participants
n=70 Participants
|
7 Participants
n=53 Participants
|
13 Participants
n=153 Participants
|
|
Type of Surgery
Aseptic Revision
|
0 Participants
n=30 Participants
|
68 Participants
n=70 Participants
|
0 Participants
n=53 Participants
|
68 Participants
n=153 Participants
|
|
Type of Surgery
DAIR
|
0 Participants
n=30 Participants
|
1 Participants
n=70 Participants
|
18 Participants
n=53 Participants
|
19 Participants
n=153 Participants
|
|
Type of Surgery
1st Stage of a 2 Stage
|
0 Participants
n=30 Participants
|
1 Participants
n=70 Participants
|
34 Participants
n=53 Participants
|
35 Participants
n=153 Participants
|
|
Type of Surgery
1 Stage
|
0 Participants
n=30 Participants
|
0 Participants
n=70 Participants
|
1 Participants
n=53 Participants
|
1 Participants
n=153 Participants
|
|
Type of Surgery
Primary
|
30 Participants
n=30 Participants
|
0 Participants
n=70 Participants
|
0 Participants
n=53 Participants
|
30 Participants
n=153 Participants
|
|
Calprotectin POC Result
Low Risk
|
29 Participants
n=30 Participants
|
61 Participants
n=70 Participants
|
1 Participants
n=53 Participants
|
91 Participants
n=153 Participants
|
|
Calprotectin POC Result
Moderate Risk
|
0 Participants
n=30 Participants
|
6 Participants
n=70 Participants
|
0 Participants
n=53 Participants
|
6 Participants
n=153 Participants
|
|
Calprotectin POC Result
High Risk
|
1 Participants
n=30 Participants
|
3 Participants
n=70 Participants
|
52 Participants
n=53 Participants
|
56 Participants
n=153 Participants
|
|
Calprotectin ELISA Result
Low Risk
|
29 Participants
n=30 Participants
|
58 Participants
n=70 Participants
|
1 Participants
n=53 Participants
|
88 Participants
n=153 Participants
|
|
Calprotectin ELISA Result
Moderate Risk
|
0 Participants
n=30 Participants
|
9 Participants
n=70 Participants
|
0 Participants
n=53 Participants
|
9 Participants
n=153 Participants
|
|
Calprotectin ELISA Result
High Risk
|
1 Participants
n=30 Participants
|
3 Participants
n=70 Participants
|
52 Participants
n=53 Participants
|
56 Participants
n=153 Participants
|
|
Sinus Tract
|
0 Participants
MSIS criteria was only applied to septic and aseptic cases.
|
0 Participants
n=70 Participants • MSIS criteria was only applied to septic and aseptic cases.
|
14 Participants
n=53 Participants • MSIS criteria was only applied to septic and aseptic cases.
|
14 Participants
n=123 Participants • MSIS criteria was only applied to septic and aseptic cases.
|
|
Cultures
2 or more positive cultures
|
—
|
0 Participants
n=70 Participants • Cultures were not ordered on primary TKAs as they are not standard of care
|
33 Participants
n=53 Participants • Cultures were not ordered on primary TKAs as they are not standard of care
|
33 Participants
n=123 Participants • Cultures were not ordered on primary TKAs as they are not standard of care
|
|
Cultures
1 positive culture
|
—
|
9 Participants
n=70 Participants • Cultures were not ordered on primary TKAs as they are not standard of care
|
47 Participants
n=53 Participants • Cultures were not ordered on primary TKAs as they are not standard of care
|
56 Participants
n=123 Participants • Cultures were not ordered on primary TKAs as they are not standard of care
|
|
Cultures
0 positive cultures
|
—
|
62 Participants
n=70 Participants • Cultures were not ordered on primary TKAs as they are not standard of care
|
6 Participants
n=53 Participants • Cultures were not ordered on primary TKAs as they are not standard of care
|
68 Participants
n=123 Participants • Cultures were not ordered on primary TKAs as they are not standard of care
|
|
Histopathology
Positive
|
—
|
3 Participants
n=66 Participants • Histopathology was not ordered on primary TKAs as they are not standard of care. It was not ordered for a number septic and aseptic cases due to the individual preferences of the surgeon.
|
33 Participants
n=38 Participants • Histopathology was not ordered on primary TKAs as they are not standard of care. It was not ordered for a number septic and aseptic cases due to the individual preferences of the surgeon.
|
36 Participants
n=104 Participants • Histopathology was not ordered on primary TKAs as they are not standard of care. It was not ordered for a number septic and aseptic cases due to the individual preferences of the surgeon.
|
|
Histopathology
Negative
|
—
|
63 Participants
n=66 Participants • Histopathology was not ordered on primary TKAs as they are not standard of care. It was not ordered for a number septic and aseptic cases due to the individual preferences of the surgeon.
|
5 Participants
n=38 Participants • Histopathology was not ordered on primary TKAs as they are not standard of care. It was not ordered for a number septic and aseptic cases due to the individual preferences of the surgeon.
|
68 Participants
n=104 Participants • Histopathology was not ordered on primary TKAs as they are not standard of care. It was not ordered for a number septic and aseptic cases due to the individual preferences of the surgeon.
|
PRIMARY outcome
Timeframe: Day of surgerylateral flow point of care test
Outcome measures
| Measure |
Primary Total Knee Arthroplasty
n=30 Participants
There will be n=30 primary TKA patients included in the study, to provide a baseline level for calprotectin.
Calprotectin test: Calprotectin will be measured both by ELISA and point of care test.
|
Aseptic Revision Total Knee Arthroplasty
n=70 Participants
There will be n=70 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: Calprotectin will be measured both by ELISA and point of care test.
|
Revision Septic Total Knee Arthroplasty
n=53 Participants
There will be n=50 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: Calprotectin will be measured both by ELISA and point of care test.
|
|---|---|---|---|
|
Calprotectin POC
Positive at >50 mg/L
|
1 Participants
|
3 Participants
|
52 Participants
|
|
Calprotectin POC
Negative at >50 mg/L
|
29 Participants
|
67 Participants
|
1 Participants
|
|
Calprotectin POC
Positive at >14 mg/L
|
1 Participants
|
9 Participants
|
52 Participants
|
|
Calprotectin POC
Negative at >14 mg/L
|
29 Participants
|
61 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day of surgeryELISA analysis
Outcome measures
| Measure |
Primary Total Knee Arthroplasty
n=30 Participants
There will be n=30 primary TKA patients included in the study, to provide a baseline level for calprotectin.
Calprotectin test: Calprotectin will be measured both by ELISA and point of care test.
|
Aseptic Revision Total Knee Arthroplasty
n=70 Participants
There will be n=70 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: Calprotectin will be measured both by ELISA and point of care test.
|
Revision Septic Total Knee Arthroplasty
n=53 Participants
There will be n=50 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: Calprotectin will be measured both by ELISA and point of care test.
|
|---|---|---|---|
|
Calprotectin ELISA
Negative at >50 mg/L
|
29 Participants
|
67 Participants
|
1 Participants
|
|
Calprotectin ELISA
Positive at >14 mg/L
|
1 Participants
|
12 Participants
|
52 Participants
|
|
Calprotectin ELISA
Negative at >14 mg/L
|
29 Participants
|
58 Participants
|
1 Participants
|
|
Calprotectin ELISA
Positive at >50 mg/L
|
1 Participants
|
3 Participants
|
52 Participants
|
POST_HOC outcome
Timeframe: From completion of first patient's ELISA and POC test to last patient's ELISA and POC testPopulation: Primary TKAs were no analyzed as AUC is a binary analysis representing the accuracy of predicting the correct diagnosis, ie (an aseptic is an negative, or a septic is positive). Arms/Groups are combined as the data represents the accuracy of all septics and aseptics combined at a given threshold for either the POC or ELISA test. This assessment was pre-specified to combine Arms.
Area under the curve (AUC) was calculated using receiver operator characteristic (ROC) curve using the two cut offs (\>14 mg/L and \>50 mg/L) for both the ELISA and POC tests. Data were collected intraoperatively during the patient's arthroplasty surgery. AUC - ROC curve is a performance measurement for classification problem at various thresholds settings. ROC is a probability curve and AUC represents degree or measure of separability. It tells how much model is capable of distinguishing between classes. Higher the AUC, better the model is at predicting 0s as 0s (aseptics that are negative) and 1s as 1s (septics that are positive). 1.000 represents accurately predicting each aseptic as negatve and each septic as positive. While a 0.000 represents accurately predicting each aseptic as positive and each septic as negative.
Outcome measures
| Measure |
Primary Total Knee Arthroplasty
There will be n=30 primary TKA patients included in the study, to provide a baseline level for calprotectin.
Calprotectin test: Calprotectin will be measured both by ELISA and point of care test.
|
Aseptic Revision Total Knee Arthroplasty
n=123 Participants
There will be n=70 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: Calprotectin will be measured both by ELISA and point of care test.
|
Revision Septic Total Knee Arthroplasty
There will be n=50 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: Calprotectin will be measured both by ELISA and point of care test.
|
|---|---|---|---|
|
Area Under the Curve
POC Test >50 mg/L
|
—
|
0.969 probability
Interval 0.934 to 1.0
|
—
|
|
Area Under the Curve
POC Test >14 mg/L
|
—
|
0.926 probability
Interval 0.875 to 0.978
|
—
|
|
Area Under the Curve
ELISA Test >50 mg/L
|
—
|
0.969 probability
Interval 0.934 to 1.0
|
—
|
|
Area Under the Curve
ELISA Test >14 mg/L
|
—
|
0.905 probability
Interval 0.847 to 0.962
|
—
|
Adverse Events
Primary Total Knee Arthroplasty
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Aseptic Revision Total Knee Arthroplasty
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Revision Septic Total Knee Arthroplasty
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Alison Klika
Cleveland Clinic Arthroplasty Research Group
Phone: 4123017914
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place