THE MERETEK UBT BREATH TEST FOR H.PYLORI

K972352 · Meretek Diagnostics, Inc. · MSQ · Oct 29, 1997 · Microbiology

Device Facts

• Record ID: K972352
• Device Name: THE MERETEK UBT BREATH TEST FOR H.PYLORI
• Applicant: Meretek Diagnostics, Inc.
• Product Code: MSQ · Microbiology
• Decision Date: Oct 29, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3110
• Device Class: Class 1

Indications for Use

The MERETEK UBT™ Breath Test Collection Kit is intended for use in the qualitative detection of urease associated with Helicobacter pylori in the human stomach and as an aid in the initial diagnosis and post-treatment monitoring of Helicobacter pylori infection in adult patients. For this purpose, the system utilizes a Gas Isotope Ratio Mass Spectrometer ("GIRMS") for the measurement of the ratio of 13CO2 to 12CO2 in breath samples. For administration by health care professionals. To be administered under a physician's supervision.

Device Story

The MERETEK UBT is a diagnostic kit for H. pylori detection. Patient ingests 125 mg of 13C-urea; if gastric H. pylori urease is present, urea decomposes into 13CO2 and NH4+. 13CO2 is absorbed into blood and exhaled. Breath samples (baseline and post-ingestion) are collected in tubes and analyzed via Gas Isotope Ratio Mass Spectrometry (GIRMS) at a laboratory. The system measures the 13CO2/12CO2 ratio. Healthcare professionals administer the test under physician supervision. Results assist clinicians in diagnosing infection and monitoring treatment efficacy post-therapy. The test provides a non-invasive method to confirm H. pylori status, supporting clinical decisions regarding antibiotic or proton pump inhibitor treatment regimens.

Clinical Evidence

Two independent double-blind clinical trials (n=499 adults with duodenal ulcer disease) compared the MERETEK UBT® against histopathology, microbiological culture, and CLOtest®. For initial diagnosis, sensitivity was 95.2% (95% CI: 92.6, 97.0) and specificity was 89.7% (95% CI: 72.6, 97.8) compared to combined endoscopic methods. For post-treatment monitoring (≥4 weeks post-therapy), combined sensitivity was 95.5% (95% CI: 93.0, 97.2) and specificity was 96.0% (95% CI: 93.0, 98.0). No adverse events were reported.

Technological Characteristics

Diagnostic kit includes 13C-urea, test meal, and breath collection tubes. Principle of operation: Gas Isotope Ratio Mass Spectrometry (GIRMS) to measure 13CO2/12CO2 ratio in breath samples. Analysis performed at centralized clinical laboratories. No software algorithm details provided beyond mass spectrometry measurement.

Indications for Use

Indicated for adult patients for the qualitative detection of urease associated with Helicobacter pylori in the stomach, aiding in initial diagnosis and post-treatment monitoring of H. pylori infection. To be used at least four weeks following completion of therapy for monitoring.

Regulatory Classification

Identification

Campylobacter fetus serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identify Campylobacter fetus from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium and provides epidemiological information on these diseases. Campylobacter fetus is a frequent cause of abortion in sheep and cattle and is sometimes responsible for endocarditis (inflammation of certain membranes of the heart) and enteritis (inflammation of the intestines) in humans.

Predicate Devices

• The MERETEK UBT® Breath Test for Detection of H. pylori (K952220)

Submission Summary (Full Text)

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## 510(k) SUMMARY

## The MERETEK UBT® Breath Test for Detection of H.pylori

#### Applicant's Name, Address, Contact Person, and Date of Preparation A.

MERETEKdiagnostics, inc. 618 Grassmere Park Drive Suite 20 Nashville, Tennessee 37211

Please direct any requests for information to:

Mr. Kerry C. Bush Vice President and Chief Operating Officer MERETEKdiagnostics, inc. 618 Grassmere Park Drive Suite 20 Nashville, Tennessee 37211

[phone] Phone: [phone] Fax:

This 510(k) summary was prepared October, 1997.

#### Device Name and Classification B.

Trade Name of the Device: The MERETEK UBT® Breath Test for H.pylori

Common Name of the Device:

Breath Test for Helicobacter pylori; UBT

### Classification:

Campylobacter pylori (presence) Name: Campylobacter pylori was officially renamed Helicobacter pylori in 1989. Note: Class: I

#### C. The Predicate Device

Since this Premarket Notification is for labeling modification to a cleared device (K952220), the predicate device is the device itself: The MERETEK UBT® Breath Test for Detection of H. pylori.

#### Description of the Device D.

The device is a combination kit diagnostic drug/device composed of the following principle components:

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Test Meal (of approximately 220 calories) Pranactin Diagnostic Drug Dosage Sterile Water Breath Bag Evacuated Breath Specimen Collection Tubes

### Principle of the Test

In the MERETEK UBT® Breath Test for H. pylori, 125 mg of reconstituted 13C-urea is ingested by the patient. In the presence of urease associated with gastric H. pylori, 13Curea is decomposed to 13CO2 and NH4+ according to the following equation:

> (NH2)213CO + H2O + 2H+ - 40Urease > 13CO2 + 2NH4+ 13C-urea

The 13CO2 is absorbed in the blood, then exhaled in the breath. This results in an increase in the ratio of 13CO2 to 12CO2 in a TEST breath sample compared to a BASELINE sample taken before the Pranactin® solution was consumed. Analysis of the breath samples is performed by Gas Isotope Ratio Mass Spectrometry ("GIRMS") at Meretek's clinical laboratories or at other qualified laboratories licensed by MERETEKdiagnostics, inc.

#### E. Intended Use

The MERETEK UBT® Breath Test Collection Kit is intended for use in the qualitative detection of urease associated with Helicobacter pylori in the human stomach and as an aid in the initial diagnosis and post-treatment monitoring of Helicobacter pylori infection in adult patients. The test may be used for monitoring treatment if used at least four weeks following completion of therapy. For these purposes, the system utilizes a Gas Isotope Ratio Mass Spectrometer ("GIRMS") for the measurement of the ratio of 13CO2 to 12CO2 in breath samples.

For administration by health care professionals. To be administered under a physician's supervision.

#### Technological Characteristics of the Device and the Predicate Device F.

The technological characteristics of the subject device are the same as the predicate device.

### G. Clinical Testing

### Experimental Design

The method comparison data presented here were collected from two (2) independent double blind clinical field trials which involved treatment of H.pylori infection. The studies included 499 adult patients with duodenal ulcer disease at 75 clinical sites in the United States. Patients were tested for H.pylori infection initially (using histopathology, microbiological culture, CLOtest®, and the MERETEK UBT®), and at various posttreatment intervals throughout the study (using histopathology, microbiological culture, and the MERETEK UBT®). In these clinical trials patients were treated with various

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combinations of clarithromycin, omeprazole and placebo. Note, however, that there is no evidence that differing treatment regimens affect the performance of the MERETEK UBT®.

### Results

Method comparison results are presented in two-way contingency tables. In tables 1, 2 and 3, the MERETEK UBT® Breath Test results are compared with the CLOtest®, histology and with the combined endoscopic method results for the initial patient visit. In table 4, the MERETEK UBT® Breath Test results are compared with the combined endoscopic method results (histology and culture) for the post-treatment visits which occurred four weeks or more after end of treatment. The exact binomial distribution was used to calculate the lower and upper limits of the 95% confidence intervals of the performance statistics. The confidence intervals are entered in parentheses following the point estimate of the statistic.

### Performance Characteristics for Initial Diagnosis

#### Table 1. Comparison with CLOtest® for Initial Visit

| Meretek UBT® Breath Test results | | | |
|----------------------------------|----------|----------|-------|
| CLOtest® | positive | negative | Total |
| positive | 397 | 31 | 428 |
| negative | 1 | 16 | 17 |
| Total | 398 | 47 | 445 |

Relative sensitivity: 92.8 % [95% CI: (89.9,95.0)] Relative specificity: 94.1 % [95% CI: (71.3,99.9)]

| Table 2. Comparison with histology for Initial Visit | | | | | |
|------------------------------------------------------|--|--|--|--|--|
|------------------------------------------------------|--|--|--|--|--|

| Meretek UBT® Breath Test results | | | |
|----------------------------------|----------|----------|-------|
| Histology | positive | negative | Total |
| positive | 394 | 20 | 414 |
| negative | 3 | 27 | 30 |
| Total | 397 | 47 | 444 |

Relative sensitivity: 95.2 % [95% CI: (92.6,97.0)] Relative specificity: 90.0 % [95% CI: (73.5,97.9)]

- Table 3. Comparison with combined endoscopic methods for Initial Visit (Combined endoscopic methods used were CLOtest®, histology and culture per DAIDP guidelines for pre-treatment diagnosis.)

| Meretek UBT® Breath Test results | | | |
|----------------------------------|----------|----------|-------|
| Endoscopy | positive | negative | Total |
| positive | 395 | 20 | 415 |
| negative | 3 | 26 | 29 |
| Total | 398 | 46 | 444 |

Sensitivity: 95.2 % [95% CI: (92.6,97.0)] Specificity: 89.7 % [95% CI: (72.6,97.8)}

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Performance Characteristics for Post-Treatment Monitoring

| | 1 Month<br>EOT | | 3 Months<br>EOT | | 6 Months<br>EOT | | 1-6 Months<br>Combined | |
|-------------|----------------|-----|-----------------|-----|-----------------|-----|------------------------|-----|
| Endoscopy | pos | neg | pos | neg | pos | neg | pos | neg |
| positive | 187 | 6 | 123 | 8 | 91 | 5 | 401 | 19 |
| negative | 5 | 97 | 4 | 87 | 2 | 80 | 11 | 264 |
| Sensitivity | 96.9 | | 93.9 | | 94.8 | | 95.5 | |
| (95% CI) | (93.4,98.8) | | (88.3,97.3) | | (88.3,98.3) | | (93.0,97.2) | |
| Specificity | 95.1 | | 95.6 | | 97.6 | | 96.0 | |
| (95% CI) | (88.9,98.4) | | (89.1,98.8) | | (91.5,99.7) | | (93.0,98.0) | |

## Table 4. Comparison with combined endoscopic methods * for Post-Treatment Visits (four weeks or more after End of Treatment (EOT))

## * Combined endoscopic methods used were histology and culture per DAIDP guidelines for post-treatment monitoring)

Please note that the post-treatment performance characteristics at 1, 3 and 6 months after therapy are not statistically different. Therefore, the single best estimates of sensitivity and specificity are presented in the 1-6 Months Combined column.

## Negative Predictive Value (NPV) for Post-Treatment Monitoring

Given the post-treatment sensitivity (95.5%) and specificity (96.0%) observed in these studies, and assuming a treatment efficacy of 90% (10% prevalence of residual H.pylori infection), the NPV of the MERETEK UBT® is greater than 99%. When efficacy of treatment drops to 50%, the NPV is still greater than 95%.

## H. Adverse Events

There were no adverse events related to the use of the MERETEK UBT® reported during the clinical trials.

#### I. Conclusion

The MERETEK UBT® is safe and effective for its intended use in the qualitative detection of urease associated with Helicobacter pylori in the human stomach and as an aid in the initial diagnosis and post-treatment monitoring of Helicobacter pylori infection in adult patients.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 2 9 1997

Claudia T. Hitchcock President & Chief Executive Officer Meretek Diagnostics, Inc. 618 Grassmere Park Drive Suite 20 Nashville, TN 37211

Re: K972352

> Trade Name: The Meretek UBT™ Breath Test for Helicobacter pylori Regulatory Class: II Product Code: MSQ Dated: September 2, 1997 Received: September 3, 1997

Dear Mr. Bush:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. -Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number [phone] or at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely vours.

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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# X. STATEMENT OF INDICATIONS FOR USE

Device Name:

MERETEK UBT™ Breath Test For H.pylori

Indications for Use:

The MERETEK UBT™ Breath Test Collection Kit is intended for use in the qualitative detection of urease associated with Helicobacter pylori in the human stomach and as an aid in the initial diagnosis and post-treatment monitoring of Helicobacter pylori infection in adult patients. For this purpose, the system utilizes a Gas Isotope Ratio Mass Spectrometer ("GIRMS") for the measurement of the ratio of 13CO, to 12CO2 in breath samples. ----------------------------------------

For administration by health care professionals. To be administered under a physician's supervision.

Prescription Use: Yes

Alan Cooper

on Sign-Off Division of Clinical Laboratory Devices 510(k) Number

Prescription Use (Per 21 CFR 801.109)

OR

Over-The Counter Use

(Optional Format 1-2-96)