STA LIATEST D-DI

K141144 · Diagnostica Stago · DAP · Sep 3, 2014 · Hematology

Device Facts

• Record ID: K141144
• Device Name: STA LIATEST D-DI
• Applicant: Diagnostica Stago
• Product Code: DAP · Hematology
• Decision Date: Sep 3, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7320
• Device Class: Class 2

Indications for Use

The STA® - Liatest® D-Di kit is an immuno-turbidimetric assay for the quantitative determination of D-dimer in venous plasma (in 3.2% sodium citrate) for use on STA-R®, STA Compact® and STA Satellite® analyzers by professional laboratory personnel. The STA® - Liatest® D-Di is intended for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) and as an aid in the diagnosis of deep venous thrombosis (DVT) in outpatients suspected of PE or DVT.

Device Story

STA® - Liatest® D-Di is an in vitro diagnostic immuno-turbidimetric assay for quantitative D-dimer measurement in venous plasma. Device utilizes latex microparticles coated with mouse monoclonal anti-human D-dimer antibodies (8D2 and 2.1.16). When mixed with patient plasma, antigen-antibody reaction causes agglutination, increasing turbidity; measured photometrically at 540 nm. Used on STA-R®, STA Compact®, and STA Satellite® analyzers in hospital or clinical laboratories by professional personnel. Results, interpreted alongside clinical pretest probability (PTP) scores, assist clinicians in excluding PE and diagnosing DVT. Benefit includes safe rule-out of PE, reducing unnecessary imaging procedures.

Clinical Evidence

Prospective multi-center study (9 sites, N=1,130) evaluated PE exclusion in outpatients with low/moderate PTP. Primary endpoints: sensitivity, specificity, NPV. Results: Sensitivity 97.0% (95% CI: 91.6-99.4%), Specificity 75.5% (95% CI: 72.8-78.1%), NPV 99.7% (95% CI: 99.2-100.0%). Study population included 1,060 prospective samples and 70 US banked frozen samples. Reference standard: imaging or 3-month follow-up.

Technological Characteristics

Immuno-turbidimetric assay; reagents include Tris buffer and microlatex particles coated with mouse monoclonal anti-human D-dimer antibodies (8D2, 2.1.16) stabilized with bovine albumin. Photometric measurement at 540 nm. Analyzers: STA-R®, STA Compact®, STA Satellite®. No direct patient contact; no sterility or biocompatibility requirements.

Indications for Use

Indicated for outpatients suspected of pulmonary embolism (PE) or deep venous thrombosis (DVT). Used in conjunction with clinical pretest probability (PTP) assessment to exclude PE and aid in DVT diagnosis.

Predicate Devices

• STA® - Liatest® D-Di (k964728)
• VIDAS® D-Dimer Exclusion™ (k040882)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k141144

B. Purpose for Submission:
Expanded indications for exclusion of pulmonary embolism (PE) to previously cleared D-dimer assay (k964728)

C. Measurand:
D-dimer

D. Type of Test:
Quantitative immuno-turbidimetric method

E. Applicant:
Diagnostica Stago

F. Proprietary and Established Names:
STA® - Liatest® D-Di

G. Regulatory Information:

1. Regulation section:
21 §CFR 864.7320, Fibrinogen/fibrin degradation products assay

2. Classification:
Class II

3. Product code:
DAP, Fibrinogen and Fibrin Spilt Products, Antigen, Antiserum, Control

4. Panel:
81 Hematology

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H. Intended Use:

1. Intended use(s):

The STA® - Liatest® D-Di kit is an immuno-turbidimetric assay for the quantitative determination of D-dimer in venous plasma (in 3.2% sodium citrate) for use on STA-R®, STA Compact® and STA Satellite® analyzers by professional laboratory personnel. The STA® - Liatest® D-Di is intended for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) and as an aid in the diagnosis of deep venous thrombosis (DVT) in outpatients suspected of PE or DVT.

2. Indication(s) for use:

Same as intended use

3. Special conditions for use statement(s):

For prescription use only

4. Special instrument requirements:

STA-R® (k983460)
STA Compact® (k961579)
STA Satellite® (k082248)

I. Device Description:

The STA® - Liatest® D-Di assay is a quantitative test for the turbidimetric immuno-assay determination of fibrin degradation products in citrated plasma. The STA® - Liatest® D-Di test kits contain two liquid reagents:

- 6 x 5-ml vials of ready-for-use Tris buffer
- 6 x 6-ml vials of a suspension of microlatex particles coated with two different mouse monoclonal anti-human D-dimer antibodies (8D2 and 2.1.16) stabilized with bovine albumin.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Diagnostica, Stago STA® - Liatest®
bioMérieux, VIDAS® D-Dimer Exclusion™

2. Predicate 510(k) number(s):

k964728
k040882

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3. Comparison with predicate:

Diagnostica Stago STA® - Liatest® D-Di

| Similarities | | |
| --- | --- | --- |
| Item | Device STA® - Liatest® D-Di | Predicate, k964728 STA® - Liatest® D-Di |
| Analyte | D-dimer | D-dimer |
| Assay method | Immuno-turbidimetric method | Immuno-turbidimetric method |
| Cut-off | 0.5 μg/mL (FEU) | 0.5 μg/mL (FEU) |
| Test principle | Immuno-turbidimetric method based on the measurement of light absorbance (at 540 nm) produced by a suspension of microlatex particles coated with specific mouse anti-human D-dimer monoclonal antibodies. | Immuno-turbidimetric method based on the measurement of light absorbance (at 540 nm) produced by a suspension of microlatex particles coated with specific mouse anti-human D-dimer monoclonal antibodies. |
| Analyzers | IVD analyzers of the STA® line: STA-R® k983460, STA Compact® k961579, and STA Satellite® k082248. | IVD analyzers of the STA® line: STA-R® k983460), STA Compact® k961579, and STA Satellite® k082248. |
| Differences | | |
| --- | --- | --- |
| Item | Device STA® - Liatest® D-Di | Predicate, k964728 STA® - Liatest® D-Di |
| Indication for Use | Indications for Use The STA® - Liatest® D-Di kit is an immuno-turbidimetric assay for the quantitative determination of D-dimer in venous plasma (in 3.2% sodium citrate) for use on STA-R®, STA Compact® and STA Satellite® analyzers by professional laboratory personnel. The STA® - Liatest® D-Di is intended for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) and as an aid in the diagnosis of deep venous thrombosis (DVT) in outpatients suspected of PE or DVT. | Quantitative determination of D-dimer in plasma. The assay can be used to aid in the diagnosis of deep venous thrombosis and pulmonary embolism disease. |

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- bioMérieux VIDAS® D-Dimer Exclusion™

| Similarities | | |
| --- | --- | --- |
| Item | Device STA® - Liatest® D-Di | Predicate, k040882 VIDAS® D-Dimer Exclusion™ |
| Indication for use | Quantitative determination of D-dimer in venous plasma (in 3.2% sodium citrate). The assay is intended for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) and as an aid in the diagnosis of deep venous thrombosis (DVT) in outpatients suspected of PE or DVT. | Automated quantitative test for use on the VIDAS instruments for the immunoenzymatic determination of fibrin degradation products (FbDP) in human plasma (sodium citrate) using ELFA technique (Enzyme Linked Fluorescent Assay). The assay is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of PE or DVT. |
| Analyte | D-dimer | D-dimer |
| Cut-off | 0.5 μg/mL (FEU) | 500 ng/mL (FEU) |
| Test principle | Immuno-turbidimetric method based on the measurement of light absorbance (at 540 nm) produced by a suspension of microlatex particles coated with specific mouse anti-human D-dimer monoclonal antibodies. | ELFA technique (Enzyme Linked Fluorescent Assay) |
| Analyzers | IVD analyzers of the STA® line. | VIDAS instrument. |
| Differences | | |
| --- | --- | --- |
| Item | Device STA® - Liatest® D-Di | Predicate, k040882 VIDAS® D-Dimer Exclusion™ |
| Assay method | Immuno-turbidimetric method | ELFA technique (Enzyme Linked Fluorescent Assay) |
| Test principle | Immuno-turbidimetric method based on the measurement of light absorbance (at 540 nm) produced by a suspension of microlatex particles coated with specific mouse anti-human D-dimer monoclonal antibodies. | The assay combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection step (ELFA). |

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| Differences | | |
| --- | --- | --- |
| Item | Device
STA® - Liatest® D-Di | Predicate, k040882
VIDAS® D-Dimer Exclusion™ |
| Analyzers | IVD analyzers of the STA®
line: STA-R®, STA Compact®,
and STA Satellite®. | VIDAS instrument |

## K. Standard/Guidance Document Referenced (if applicable):

CLSI H59-A Quantitative D-dimer for the exclusion of venous thromboembolic disease; Approved Guideline

## L. Test Principle:

The assay is based on the change in turbidity of a microparticle suspension that is measured by photometry. A suspension of latex microparticles, coated by covalent bonding with monoclonal antibodies specific for D-dimer is mixed with the test plasma for which the D-dimer level is to be assayed. An antigen-antibody reaction takes place, leading to an agglutination of the latex microparticles which causes an increase in turbidity of the reaction medium. This increase in turbidity is reflected by an increase in absorbance, the latter being measured photometrically. The increase in absorbance is a function of the D-dimer level present in the test sample. D-dimer levels are expressed in fibrinogen equivalent units (FEU).

## M. Performance Characteristics:

1. **Analytical performance:**
a. **Precision/Reproducibility:**
Refer to 510(k) cleared device - k964728
b. **Linearity/assay reportable range:**
Refer to 510(k) cleared device - k964728
c. **Traceability, Stability, Expected values (controls, calibrators, or methods):**
Refer to 510(k) cleared device - k964728
d. **Detection limit:**
Refer to 510(k) cleared device - k964728
e. **Analytical specificity:**
Refer to 510(k) cleared device - k964728
f. **Assay cut-off:**
Refer to 510(k) cleared device - k964728

2. **Comparison studies:**
a. **Method comparison with predicate device:**

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Not applicable. Clinical study performed to determine exclusion of pulmonary embolism (PE).

b. Matrix comparison:
Refer to 510(k) cleared device - k964728

3. Clinical studies:

a. Clinical Sensitivity:

i. Prospective study: A clinical multi-center study (9 sites over North America and Europe) was performed to demonstrate the ability of STA® - Liatest® D-Di to exclude pulmonary embolism (PE) using samples of outpatients enrolled in emergency departments prospectively and consecutively. All patients suspected of having a PE were evaluated with the Wells' model to assess their pre-test probability (PTP) score: low, moderate, or high.

Patients with a low or moderate PTP score were considered for D-dimer testing. Those with a positive D-dimer result were referred to imaging studies. Those with negative a D-dimer result were considered as not having PE and assigned to a three-month follow up to evaluate a potential development of PE and were included for analysis. Patients with high PTP were sent for imaging studies and not included in the study population.

The prospective study population was enriched with US banked frozen samples collected from a similar PE clinical study.

Sensitivity, specificity and negative predictive value (NPV) with upper and lower limit of 95% confidence intervals (CI) were calculated with the STA® - Liatest® D-Di using the previously cleared clinical cut-off of 0.50 µg/mL (FEU) in the (low and moderate) PTP group of patients:

- US sites: A total of 358 samples of patients from two US clinical centers were used for analysis.

| US Prospective | Reference (Imaging or 3-month follow-up) | | | |
| --- | --- | --- | --- | --- |
| | | Positive | Negative | Total |
| D-Dimer | Positive | 8 | 78 | 86 |
| | Negative | 1 | 271 | 272 |
| | Total | 9 | 349 | 358 |
| Sensitivity = 88.9% | | 95% CI: 51.8% to 99.7% | | |
| Specificity = 77.7% | | 95% CI: 72.9% to 81.9% | | |
| NPV = 99.6% | | 95% CI: 98.0% to 100.0% | | |
| PPV = 9.3% | | 95% CI: 4.1% to 17.5% | | |

- Out of US (OUS) sites: A total of 702 samples of patients from seven OUS

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clinical centers were used for analysis.

| OUS Prospective | Reference (Imaging or 3-month follow-up) | | | |
| --- | --- | --- | --- | --- |
| | | Positive | Negative | Total |
| D-Dimer | Positive | 74 | 145 | 219 |
| | Negative | 1 | 482 | 483 |
| | Total | 75 | 627 | 702 |
| Sensitivity = 98.7% | | 95% CI: 92.8% to 100.0% | | |
| Specificity = 76.9% | | 95% CI: 73.4% to 80.1% | | |
| NPV = 99.8% | | 95% CI: 98.9% to 100.0% | | |
| PPV = 33.8% | | 95% CI: 27.6% to 40.5% | | |

ii. US banked samples: Data from banked samples were obtained from a plasma bank in a similar previous prospective clinical PE study in four US sites. STA® - Liatest® D-Di was performed on frozen plasma samples from patients diagnosed with PE. Sample stability was assessed by comparison with results obtained prior to freezing (fresh specimens). The results of the stability study were found to be acceptable. Data from the stability study was used to enrich data of the prospective study with positive and negative cases. A total of 70 samples were used for analysis.

| US Banked Samples | Reference (Imaging or 3-month follow-up) | | | |
| --- | --- | --- | --- | --- |
| | | Positive | Negative | Total |
| D-Dimer | Positive | 16 | 29 | 45 |
| | Negative | 1 | 24 | 25 |
| | Total | 17 | 53 | 70 |
| Sensitivity = 94.1% | | 95% CI: 71.3% to 99.9% | | |
| Specificity = 45.3% | | 95% CI: 31.6% to 59.6% | | |

iii. Overall study population: A total of 1,130 samples of patients with a low or moderate PTP were used for final analysis; 1060 samples were from prospective study population and 70 samples were from the US banked frozen samples. The overall prevalence of PE (low and moderate PTP patients) in the prospective study population was $8.4\%$ with $2.7\%$ in the US population and $11.4\%$ in the OUS population.

Demographics:

Ethnicity: Caucasian $81\%$ , black $13.1\%$ , other $5.9\%$
Age: 22-62 years of age
- Gender: $44.4\%$ male, $55.4\%$ female

| Overall Study | Reference (Imaging or 3-month follow-up) | | | |
| --- | --- | --- | --- | --- |
| | | Positive | Negative | Total |
| D-Dimer | Positive | 98 | 252 | 350 |
| | Negative | 3 | 777 | 780 |
| | Total | 101 | 1029 | 1130 |

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Sensitivity = 97.0% 95% CI: 91.6% to 99.40%
Specificity = 75.5% 95% CI: 72.8% to 78.1%
NPV = 99.7% 95% CI: 99.2% to 100.0%
PPV = 25.5% 95% CI: 23.5% to 27.7%

b. Clinical specificity:
See 3.a. above for clinical specificity results.

c. Other clinical supportive data (when a. and b. are not applicable):

4. Clinical cut-off:
STA® Liatest® D-Di cut-off is 0.50 µg/mL (FEU); this cut-off was previously established and evaluated in the clearance for k964728.
- Negative if sample level is < 0.50 µg/mL (FEU)
- Positive if sample level is ≥ to 0.50 µg/mL (FEU)

5. Expected values/Reference range:
Same as clinical cut-off 0.50 µg/mL (FEU)

N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.