(124 days)
Not Found
No
The device description and performance studies focus on a standard enzyme immunoassay and statistical analysis (multivariate logistic-regression models) of the results, with no mention of AI or ML.
No
The device is intended for diagnostic purposes, specifically for the quantitative determination of myeloperoxidase in human plasma to evaluate patients at risk for major adverse cardiac events. It does not provide therapy or treatment.
Yes
The CardioMPO Test is intended for the quantitative determination of myeloperoxidase in human plasma, to be used in conjunction with clinical history, ECG, and cardiac biomarkers to evaluate patients presenting with chest pain who are at risk for major adverse cardiac events. This explicitly states its purpose in aiding in the evaluation and assessment of a medical condition.
No
The device description clearly outlines a "sandwich enzyme immunoassay" comprised of reagent kits, calibrator kits, and control kits, all of which are physical components used in a laboratory setting to perform a chemical reaction and spectrophotometric analysis. This is not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "quantitative determination of myeloperoxidase in human plasma" to "evaluate patients presenting with chest pain that are at risk for major adverse cardiac events." This involves testing a sample taken from the human body (plasma) to provide information about a medical condition.
- Device Description: The description details a laboratory-based assay (enzyme immunoassay) that uses reagents, calibrators, and controls to measure a specific analyte (myeloperoxidase) in a biological sample (plasma). This is a typical description of an in vitro diagnostic test.
- Components: The kit includes reagents, calibrators, and controls, which are standard components of IVD kits used for quantitative measurements.
- Testing Process: The description outlines a laboratory procedure involving adding samples and reagents to a microtiter plate, incubation, washing, and spectrophotometric measurement. This is a standard process for in vitro diagnostic assays.
- Intended User/Care Setting: The intended user is a "Professional Laboratory," which is where IVD tests are typically performed.
All these factors align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological state, state of health, or disease.
N/A
Intended Use / Indications for Use
The CardioMPO Test is an enzyme immunoassay intended for the quantitative determination of myeloperoxidase in human plasma, to be used in conjunction with clinical history, ECG and cardiac biomarkers to evaluate patients presenting with chest pain that are at risk for major adverse cardiac events, including myocardial infarction, need for revascularization, or death.
The CardioMPO™ Test is comprised of the CardioMPO Reagent Kit, the CardioMPO Calibrator Kit, and the CardioMPO Control Kit.
The CardioMPO Reagent Kit is an enzyme immunoassay intended for the quantitative determination of myeloperoxidase in human plasma, to be used in conjunction with clinical history, ECG and cardiac biomarkers to evaluate patients presenting with chest pain that are at risk for major adverse cardiac events, including myocardial infarction, need for revascularization, or death.
The PrognostiX CardioMPO Calibrator Kit is intended for use with the CardioMPO Reagent Kit to establish a calibration curve that is used to determine MPO concentration.
The PrognostiX CardioMPO Control Kit is intended for use with the CardioMPO Reagent Kit as an assayed quality control sample to monitor and evaluate the precision and accuracy of the CardioMPO Test.
Product codes (comma separated list FDA assigned to the subject device)
NTV, JJX, JIS
Device Description
The CardioMPO Test is a sandwich enzyme immunoassay that uses two highly specific antibodies, one monoclonal and one polyclonal, and an enzyme labeled anti-rabbit IgG antibody for the measurement of MPO concentration in human plasma. The CardioMPO Test is comprised of the CardioMPO Reagent Kit, the CardioMPO Calibrator Kit, and the CardioMPO Control Kit.
The CardioMPO Reagent Kit contains the following: a microtiter plate coated with a monoclonal anti-MPO antibody; a solution of primary polyclonal rabbit anti-MPO antibody; a solution of secondary goat anti-rabbit IgG antibody labeled with horseradish peroxidase solution; TMB substrate solution; Stop Solution; Wash Buffer Concentrate; Assay Buffer; and plate sealers.
The CardioMPO Calibrator Kit contains six Calibrators comprised of human MPO in a phosphatebuffered matrix containing proteins, detergents, and stabilizers. Calibrators are intended to establish a calibration curve that is used to determine MPO concentration. Calibrator values are provided on individual Calibrator labels. Calibrators are provided ready-to-use.
The CardioMPO Control Kit contains three Controls comprised of human MPO in a human plasma matrix. Controls are intended to monitor and evaluate the precision and accuracy of the CardioMPO Test. Ranges are provided on individual Control labels. Controls are freated in the same manner as patient samples.
Calibrators are added directly to the appropriate wells of the Microtiter Plate. Assay Buffer is added to all wells that are intended for Control or sample analysis. Aliquots of Controls or samples are added to the appropriate wells and the plate is incubated for 60 minutes at 20-26°C. The wells are then washed with Wash Buffer to remove antigens not specifically bound to the immobilized antibody.
A yellow primary polyclonal rabbit anti-MPO antibody is added to each well and incubated for 60 minutes at 20-26°C. This antibody binds to the MPO captured on the plate. The plate is again washed with Wash Buffer to remove unbound primary antibody.
A blue secondary goat anti-rabbit IgG antibody, labeled with the enzyme horseradish peroxidase (HRP), is then added to each well and incubated for 30 minutes at 20-26°C. This antibody binds to the primary antibody, and the MPO in the sample is "sandwiched" between the monoclonal antibody on the solid phase and a complex of the rabbit anti-MPO and the HRP-goat anti-rabbit IgG antibody. The wells are washed with Wash Buffer to remove unbound HRP-labeled antibody.
The substrate, tetramethylbenzidine (TMB), is then added to each well and incubated for 10 minutes at 20-26°C resulting in the development of a blue color. Color development is stopped with the addition of Stop Solution, changing the color to yellow.
The enzymatic turnover of the substrate is determined spectrophotometrically at 450 nm, preferably with correction at 630 nm, and is directly proportional to the concentration of MPO. The absorbances of the Calibrators are used to plot a standard curve of absorbance versus MPO concentration from which the MPO concentration in the Controls or samples can be determined.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
The clinical study included samples from patients aged 23 to 96 years.
Intended User / Care Setting
Professional Laboratory
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Summary of Clinical Study: 560 banked plasma samples from a prior study of patients presenting to the Emergency Department within 24 hours of the onset of chest pain (Brennan, et al, N Engl J Med 2003; 349:1595-1604). Patients were followed for the development of myocardial infarction, need for revascularization, or death over the next 30-day and 6 month interval. The incidence of MACE was assessed by follow up phone calls at 30 days and 6 months.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Sensitivity: The minimum detection limit, as calculated by interpolation of the mean plus two standard deviations of 24 replicates of the 0 pM MPO Calibrator (F), is 13 pM MPO.
Assay Precision: Total and within-run precision were determined by testing four Matrix Controls, containing human MPO in Calibrator matrix, and five Plasma Controls, containing human MPO in human lithium heparin plasma, with MPO concentrations distributed throughout the calibration range of the assay, according to NCCLS guidelines EP5-A. The nine samples were assayed in duplicate, using a single lot of reagents and Calibrators, on two separate plates per day, for twenty days. A new calibration curve was run in duplicate on each plate. Total precision in plasma samples was 8.2% and within-run precision was 5.5%.
Linearity: The CardioMPO Test was linear from 13 pM to 5223 pM MPO, within 60 pM or 9% in this interval.
Interfering Substances: No interference observed up to the indicated concentrations for acetylsalicylic acid (600 mg/L), albumin (50000 mg/L), amoxicillin (75 mg/L), bilirubin, conjugated (50 mg/L), bilirubin, unconjugated (150 mg/L), captopril (5 mg/L), ceruloplasmin (600 mg/L), cholesterol (1000 mg/L), DNA (16.7 mg/L), fenofibrate (45 mg/L), hemoglobin (1500 mg/L), sodium azide (0.50%), and triglycerides (5000 mg/L).
Interfering Antibodies: The mean recovery of MPO from samples containing heterophilic antibodies was 108% with individual recoveries ranging from 89 to 118%. No evidence of significant interference was observed due to the heterophilic antibodies tested.
Cross-reactivity: No significant cross-reaction up to the concentrations indicated for α-1 antrypsin, human; C-reactive protein, human; Lysozyme, human; IgA, human; Elastase, human; Lactoperoxidase, bovine; Lactoferrin, human; COX1, ovine; COX2, human; Thyroid peroxidase, human; Troponin I, human.
Spiking recovery: The overall recovery of spiked MPO ranged from 89% to 105% with a mean of 97%.
Dilution recovery: The mean recovery of a 1:2 dilution was 116%, with recoveries ranging from 102% to 131%. The mean recovery at dilutions of 1:4 through 1:16 rose from 132% to 145%.
Hook Effect: There is no evidence of hook effect in the CardioMPO Test up to 800,000 pM MPO.
Reference Interval: The median MPO level for subjects in the adjusted normal subject population was 193 pM and the range of results was 48 to 924 pM. The non-parametric distribution of myeloperoxidase levels in this normal population yields a two-tailed central 95% reference interval of 78 - 708 pM. The single-tailed lower 95% reference interval is 2990 pM: Odds Ratio 3.3 (95% CI: 1.7-6.4, p 2990 pM: Odds Ratio 6.9 (95% CI: 2.5-19.2, p
§ 866.5600 Low-density lipoprotein immunological test system.
(a)
Identification. A low-density lipoprotein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein in serum may aid in the diagnosis of disorders of lipid (fat) metabolism and help to identify young persons at risk from cardiovascular diseases.(b)
Classification. Class II (performance standards).
0
510(k) Summary
PrognostiX CardioMPO™ Test
This 510(k) summary is being submitted in accordance with the Safe Medical Devices Act of 1990 and 21 CFR 807.92.
General Information
| Name and Address of Applicant: | PrognostiX, Inc.
10265 Carnegie Avenue
Cleveland, OH 44106
216-445-7469
Thomas M. Jackson, Ph.D. |
|--------------------------------|--------------------------------------------------------------------------------------------------------------|
| Date Prepared: | January 5, 2005 |
| Device Trade Name: | CardioMPO™ Test |
| Common Name: | Myeloperoxidase Test |
Identification of Legally Marketed Device
diaDexus PLAC™ Test 510(k) number K030477 diaDexus, Inc. 343 Oyster Point Blvd. South San Francisco, CA 94080
Intended Use
The CardioMPO Test is an enzyme immunoassay intended for the quantitative determination of myeloperoxidase in human plasma, to be used in conjunction with clinical history, ECG and cardiac biomarkers to evaluate patients presenting with chest pain that are at risk for major adverse cardiac events, including myocardial infarction, need for revascularization, or death.
Device Description
The CardioMPO Test is a sandwich enzyme immunoassay that uses two highly specific antibodies, one monoclonal and one polyclonal, and an enzyme labeled anti-rabbit IgG antibody for the measurement of MPO concentration in human plasma. The CardioMPO Test is comprised of the CardioMPO Reagent Kit, the CardioMPO Calibrator Kit, and the CardioMPO Control Kit.
The CardioMPO Reagent Kit contains the following: a microtiter plate coated with a monoclonal anti-MPO antibody; a solution of primary polyclonal rabbit anti-MPO antibody; a solution of secondary goat anti-rabbit IgG antibody labeled with horseradish peroxidase solution; TMB substrate solution; Stop Solution; Wash Buffer Concentrate; Assay Buffer; and plate sealers.
The CardioMPO Calibrator Kit contains six Calibrators comprised of human MPO in a phosphatebuffered matrix containing proteins, detergents, and stabilizers. Calibrators are intended to establish a calibration curve that is used to determine MPO concentration. Calibrator values are provided on individual Calibrator labels. Calibrators are provided ready-to-use.
1
The CardioMPO Control Kit contains three Controls comprised of human MPO in a human plasma matrix. Controls are intended to monitor and evaluate the precision and accuracy of the CardioMPO Test. Ranges are provided on individual Control labels. Controls are freated in the same manner as patient samples.
Calibrators are added directly to the appropriate wells of the Microtiter Plate. Assay Buffer is added to all wells that are intended for Control or sample analysis. Aliquots of Controls or samples are added to the appropriate wells and the plate is incubated for 60 minutes at 20-26°C. The wells are then washed with Wash Buffer to remove antigens not specifically bound to the immobilized antibody.
A yellow primary polyclonal rabbit anti-MPO antibody is added to each well and incubated for 60 minutes at 20-26°C. This antibody binds to the MPO captured on the plate. The plate is again washed with Wash Buffer to remove unbound primary antibody.
A blue secondary goat anti-rabbit IgG antibody, labeled with the enzyme horseradish peroxidase (HRP), is then added to each well and incubated for 30 minutes at 20-26°C. This antibody binds to the primary antibody, and the MPO in the sample is "sandwiched" between the monoclonal antibody on the solid phase and a complex of the rabbit anti-MPO and the HRP-goat anti-rabbit IgG antibody. The wells are washed with Wash Buffer to remove unbound HRP-labeled antibody.
The substrate, tetramethylbenzidine (TMB), is then added to each well and incubated for 10 minutes at 20-26°C resulting in the development of a blue color. Color development is stopped with the addition of Stop Solution, changing the color to yellow.
The enzymatic turnover of the substrate is determined spectrophotometrically at 450 nm, preferably with correction at 630 nm, and is directly proportional to the concentration of MPO. The absorbances of the Calibrators are used to plot a standard curve of absorbance versus MPO concentration from which the MPO concentration in the Controls or samples can be determined.
2
Comparison of New Device to Predicate Device
The chart below identifies the similarities and differences between the PrognostiX CardioMPO Test and the predicate device, the diaDexus PLAC™ Test.
| Characteristic | PrognostiX CardioMPO Test
(Proposed) | diaDexus PLAC™ Test
(K030477) |
|-------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Quantitative in vitro diagnostic test to detect myeloperoxidase in human plasma, to be used in conjunction with clinical history, ECG and cardiac biomarkers to evaluate patients presenting with chest pain that are at risk for major adverse cardiac events, including myocardial infarction, need for revascularization, or death. | Quantitative in vitro diagnostic test for the determination of Lp-PLA2 in human plasma, to be used in conjunction with clinical evaluation and patient risk assessment as an aid in predicting risk for coronary heart disease. |
| Analyte | Myeloperoxidase | Lipoprotein-associated
phospholipase A2 |
| Sample | Lithium Heparin Plasma | EDTA Plasma |
| Methodology | ELISA | ELISA |
| Detection Method | Optical Density at 450 nm | Optical Density at 450 nm |
| Risk to Patients | Minimal Risk | Minimal Risk |
| Laboratory
Environment | Professional Laboratory | Professional Laboratory |
| Precision in plasma,
Total | 10%. A doseresponse series showed a bias of 5000 pM.
6
Hook Effect
There is no evidence of hook effect in the CardioMPO Test up to 800,000 pM MPO, roughly 150 times greater than the upper end of the reportable range and 500 times greater than the median level of patients in the clinical study.
Reference Interval
Plasma samples from a population of apparently healthy blood donors, were evaluated with the CardioMPO Test. A two-stage outlier detection scheme, a Box-Cox transformation followed by a robust outlier detection method, was used to eliminate six outliers. Since there was no significant difference in MPO levels between males (n=145) and females (n=149) after adjustment for outliers, the reference range was estimated from the adjusted normal subject population.
The median MPO level for subjects in the adjusted normal subject population was 193 pM and the range of results was 48 to 924 pM. The non-parametric distribution of mveloperoxidase levels in this normal population vields a two-tailed central 95% reference interval, corrected for the influence of outlier rejection, of 78 - 708 pM. However, in this application the more appropriate single-tailed lower 95% reference interval, again corrected for the influence of the outlier rejection method, is 0.03 ng/mL) (McErlean et al. Am J Cardiol 2000;85:421-426), C-reactive Protein (3 mg/L. >3 mg/L) (Brennan et al. N Engl J Med 2003;349:17, 1595-1604), CK-MB (≤8.8 ng/mL vs. >8.8 ng/mL) (McErlean et al. Am J Cardiol 2000;85:421-426), history of smoking, history of diabetes, history of hypertension, and history of high cholesterol. Missing covariate information on some subjects reduced the study population. The risk of MACE in all patients in the ensuing 30-day period increased with increasing quartiles of myeloperoxidase levels. Adjusted odds ratios and the percentage of patients within an MPO quartile with and without MACE at 30 days are shown in the following graph and table.
7
Risk of MACE in All Patients
Image /page/7/Figure/1 description: This image is a bar graph that shows the percentage of patients within a quartile. The x-axis shows the MPO by Quartile (pM) with the ranges 2990. The y-axis shows the percentage of patients within a quartile, ranging from 0 to 100. The graph compares the percentage of patients with MACE and without MACE in each quartile.
| MPO (pM) | MACE at 30 days, All Patients (n=523) | |||
|---|---|---|---|---|
| 2990 | ||||
| Odds Ratio | 1.0 | 2.5 | 2.8 | 3.3 |
| 95% CI | NA | 1.3-4.8 | 1.5-5.6 | 1.7-6.4 |
| p value | p = 0.007 | p = 0.0021 | p 2990. The y-axis shows the percentage of patients within a quartile from 0 to 100. The graph compares the percentage of patients with MACE and No MACE for each quartile. |
Risk of MACE in Patients Persistently Negative for Troponin T
| MACE at 30 days, TnT negative Patients (n=304) | ||||
|---|---|---|---|---|
| MPO (pM) | 2990 | |||
| Odds Ratio | 1.0 | 3.4 | 4.1 | 6.9 |
| 95% CI | NA | 1.2-9.4 | 1.5-11.4 | 2.5-19.2 |
| p value | p = 0.0194 | p = 0.007 | p |