PYtest (14C-Urea Capsules)

Following ingestion of the capsule by a patient with H.pylori, ¹⁴CO₂ excretion in the breath peaks between 10 and 15 minutes and declines thereafter with a biological half-life of about 15 minutes. ¹⁴C-urea that is not hydrolyzed by H.pylori is excreted in the urine with a half-life of approximately 12 hours. About 10% of the ¹⁴C remains in the body at 72 hours and is gradually excreted with a biological half-life of 40 days.

Clinical Studies

Two studies were performed. In both studies, patients with gastrointestinal symptoms underwent the breath test and an endoscopy. During the endoscopy, biopsy samples were taken from antral gastric mucosa for histological analysis (2 samples, Giemsa stain) and rapid urease test (1 sample, CLOtestÒ ). Breath samples were mailed to the TRI-MED lab where they were read in a liquid scintillation counter. Results were reported as disintegrations per minute (DPM). Analysis for accuracy used the ten minute breath sample. A breath sample DPM <50 was defined as a negative result. DPM ³ 200 was defined as a positive result. DPM in the range of 50-199 was classified as indeterminate.

Study 1
Of 186 patients who had histopathology and CLOtest (80 men,106 women), 53 were infected with H.pylori as determined by agreement between histology and CLOtest. The study results are summarized below:

Study #1 (n=186, Indeterminate results included)

Notes: PYtest at 10 min. was compared to the gold standard of biopsy results in which histology and CLOtest concurred. Patients who did not have both biopsy tests performed, or in whom the tests differed, were excluded from analysis. There was no statistical difference in test accuracy based on gender of patient.

Study 2
Breath tests were performed on 436 outpatients attending gastroenterology practices at sites in the United States. Seventy-six patients (40 men,36 women) who had histology and CLOtest were evaluated. The results are summarized below:

Study #2 (n=76, Indeterminate results included)

Notes: PYtest at 10 min. was compared to the gold standard of biopsy results in which histology and CLOtest concurred. Patients who did not have both biopsy tests performed, or in whom the tests differed, were excluded from analysis. There was no statistical difference in test accuracy based on gender of patient.

Indications and Usage

PYtest (¹⁴C-urea breath test) is indicated for use in the detection of gastric urease as an aid in the diagnosis of H.pylori infection in the human stomach. The test utilizes a liquid scintillation counter for the measurement of ¹⁴CO₂ in breath samples.

Contraindications

None

Warnings

None

Precautions

After the patient ingests the ¹⁴C urea capsule, the sample collected for test purposes is for in vitro diagnostic use only.

A false positive test could occur in patients who have achlorhydria. Very rarely, a false positive test may occur due to urease associated with Helicobacters other than H.pylori (i.e. Helicobacter heilmanni).

• The test has been evaluated in outpatients attending for elective endoscopy.
• Test results should be evaluated with clinical signs and patient history when diagnosing H. pylori infection.
• The performance characteristics of the test have not been established for monitoring the efficacy of antimicrobial therapies for the treatment of H.pylori infection.
• A negative result does not completely rule out the possibility of H. pylori infection. If clinical signs and patient history suggest H. pylori infection, repeat the PYtest or use an alternative diagnostic method.

Persons concerned about very low doses of radioactivity may postpone the test or may decide to use an alternative means of diagnosis. The test produces radiation exposure equal to 24 hours of normal background. In animal experiments, such low doses of radiation do not carry measurable risk.

Preclinical studies were not conducted on ¹⁴C-urea. The estimated dose equivalent received from a single administration of PYtest (1m ¹⁴C -urea) is about 0.3 mrem. An individual radiation dose of 5-10 mrem is below regulatory concern as recommended by the Nuclear Regulatory Commission.

It is necessary for the patient to fast for 6 hours before the test. The patient should also be off antibiotics and bismuth for 1 month, and proton pump inhibitors and sucralfate for 2 weeks prior to the test. Instruct the patient not to handle the capsule directly as this may interfere with the test result. The capsule should be swallowed intact. Do not chew the capsule.

No studies have been conducted with ¹⁴C- urea to evaluate its potential for carcinogenicity, impairment of fertility, or mutagenicity.

Antibiotics, proton pump inhibitors, sucralfate, and bismuth preparations are known to suppress H.pylori. Ingestion of antibiotics or bismuth within 4 weeks and proton pump inhibitors or sucralfate within 2 weeks prior to performing the test may give false negative results.

Pregnancy category C. Animal reproduction studies have not been conducted with PYtest ( ¹⁴C- urea). It is also not known whether PYtest can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PYtest should be given to a pregnant woman only if clearly needed.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PYtest is administered to a nursing woman.

Clinical studies in children have not been conducted. However, PYtest is expected to work the same in children as in adults. While the dose (1 capsule) does not need to be adjusted, the child must be able to swallow the intact capsule and blow into a straw.

Adverse Reactions

No adverse reactions were reported in clinical trials.

Overdosage

Risk from radiation is negligible even with a 1000 capsule overdose (0.3 rem). If overdose occurs the patient may drink one glass of water (150 mL) every hour to hasten excretion of the isotope. Maximum excretion of urea is achieved at a urine output of ³ 2.0 mL/min.

Dosage and Administration

For analysis at test site:

Breath Sample Collected into Vial

CAUTION - TRI-MED Specialties, Inc. does not endorse breath sample collection by this method because patients might come into direct contact with the hyamine.

• Breath test report form
• Stopwatch/Timer capable of timing an interval up to 10 minutes
• Safety trap (Figure 3)
• 1 - Straw
• 1 - 20mL scintillation vial
• Marking pen
• Pipette (10mL) for measuring fluids
• Collection fluid (2.5 cc/vial)
• Scintillation fluid (10 cc/vial)

Typical Safety Trap

Dosage

One PYtest capsule.

Procedural Notes

• Inform the patient to fast for 6 hours prior to the test.
• The patient should also be off antibiotics and bismuth for 1 month, and proton pump inhibitors and sucralfate for 2 weeks prior to the test.
• Have patient sitting at rest while doing the test.
• The capsule should not be handled directly as this may interfere with the test result.
• To avoid contamination by bacteria in the mouth, the capsule should be swallowed intact. Do not chew capsule.

Step by Step Procedure for Balloon:

Breath Sample Collection by Balloon

Breath Sample Collection by Vial:

CAUTION- Tri-Med Specialties, Inc. does not endorse the collection of breath samples by this method for patient safety reasons.

Test Analysis Procedure

General Information

• The collection fluid contains hyamine, methanol and a pH indicator. Hyamine is a corrosive caustic alkali. If you are using the vial method and collecting breath directly into the collection fluid you must supervise the patient and ensure that a safety trap is used.
• The amount of hyamine (1 mL of 1 molar) and methanol (2.5 mL) in one collection vial is not sufficient to cause serious poisoning. Local irritation to skin or mucous membranes is likely when the solution is blue. After collecting CO₂ the collection fluid turns clear. At this point it is less dangerous because the pH is near neutral.
• If the collection fluid splashes onto the skin or eyes, wash immediately with water. If the collection fluid is accidentally ingested, wash the mouth with water and have the patient drink 250mL of water immediately. Consult your poison information center for further facts on hyamine.
• Scintillation fluid comes in many formulations. It is usually a mixture of toluene and various cyclic hydrocarbons. It is flammable. Biodegradable formulations do exist. Consult your supplier if you have questions

Balloon Read on Site:

1. Add 2.5cc collection fluid to each vial.
2. Label the scintillation vial lid to match the label on the balloon.
3. Attach a needle to the inlet and outlet tubes on the pump.
4. Turn on pump. Allow to run for about 15 seconds.
5. Put needle from the rigid outlet tube in a vial until it makes bubbles in the collection fluid.
6. Pierce the label of a filled balloon with the other needle and hold it in a stable position. (Do not pierce the balloon anywhere else or it may tear. Do not squeeze the balloon.)
7. After 2-3 minutes the collection fluid should turn colorless.
8. After the collection fluid is colorless, remove the needles from the balloon and collection fluid and discard according to your facility protocol.
9. Change needles between patients.
10. Turn off pump after last patient sample is transferred.
11. Double check that the label on the vial lid matches the label on the balloon.
12. Add 10 mLs scintillation fluid to each vial and mix fluid.
13. Count the sample in liquid scintillation counter for 5 minutes or as directed by the liquid scintillation counter manufacturer. (Note that values of 50-300 CPM can occur immediately after the addition of the scintillation fluid due to chemiluminescence. Chemiluminescence decays rapidly over an hour or two and will reveal itself by falling counts. Read the sample repeatedly until values 10 minutes apart are similar. If DPM is still 50-300, you should allow the sample to settle for 12-24 hours before re-testing).
14. Include a standard and a blank control vial in each run.

Vial Read on Site:

See steps 12-14 under "Balloon read on-site".

Quality Control:

A minimum of 1 mmol of CO₂ is required to perform analysis of a breath sample. The amount of breath required to provide 1 mmol of CO₂ varies depending on the amount of CO₂ the patient is producing. Since a full balloon typically contains at least 1 mmol of CO₂, the balloon should be completely filled.

Results

Interpretation of results (10 minute sample)

DPM = Disintegrations per minute

The indeterminate result should be evaluated by repeating the PYtest or using an alternative diagnostic method. If repeat breath testing is undertaken, careful history to exclude confounding factors should be obtained. If confounding factors are identified, wait an appropriate time (refer to table 3) before repeating the PYtest.

The cutoff point of 50 DPM was determined to be the mean +3SD of results obtained in patients who did not have H.pylori.

Factors which might cause sub-optimal breath test results

Expected Values

*Note: DPM groupings were calculated on a logarithmic scale. Empty DPM groupings were not included. Chart includes all patients from Studies 1 and 2. Frequency of DPM group includes samples with DPM < Group Name.
DPM = Disintegrations per minute
Gold Standard = Agreement between histology and CLOtest

If the capsule is damaged or appears abnormal in any way, it may give inaccurate results.

How Supplied

PYtest Capsules, clear gelatin capsules each containing 1uCi of ¹⁴C-urea in unit dose packages of 1, 10 and 100.

PYtest Kit (¹⁴C-urea breath test) is also supplied as a kit containing a PYtest Capsule and breath collection equipment.

The PYtest Capsule has a shelf life of two years. The expiration date is printed on the capsule label.

PYtest Capsules and Kit should be stored at 15° - 30° C (59° - 86° F) in an area designated by each individual institution’s regulations.

Caution: Federal (U.S.A.) law prohibits dispensing without prescription.

Please call TRI-MED Specialties, Inc. at 1-800-874-6331 with any questions , or visit our web site at www.trimed.com.

ISPYC8-97 Revised: 8/11/97