Diagnose H. pylori, Treat
and Confirm Eradication
Intended Use
The BreathTek™ UBT Collection Kits
are 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"),
or a UBiT®-IR300 Infrared Spectrophotometer, 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.
Summary and Explanation
Since the isolation of the spiral urease-producing
Helicobacter pylori(H. pylori)
in 1983 by Warren and Marshall1, a significant
body of evidence has accumulated indicating that the bacteria
is an important pathogen in the upper GI tract of humans.2,3
The causal relationship between H.
pylori and chronic active gastritis, duodenal ulcer,
and gastric ulcer is well documented.4,5
Methods available for detecting active
infection of the human stomach by H.
pylori are generally divided into two general types:
Invasive and Non-invasive.
Invasive methods are so called because they include, as
a first step, an esophagogastroduodenoscopy ("EGD")
with collection of gastric biopsies. These biopsies
are then examined by one or more detection methods:
histological examination of stained tissue, microbiological
culture of the organism, or direct detection of urease
activity in the tissue (for example, the CLOtest®).
Biopsy based methods are expensive, entail some patient
risk and discomfort, and may give false negative results
due to sampling errors when colonization of the gastric
mucosa is patchy.6
The non-invasive, non-radioactive method for detecting
active
H. pylori
infection is based on the BreathTek™ UBT which is described
in the next section.
Several serological tests that detect serum antibodies
to H. pylori are commercially
available. A positive result with these tests cannot
distinguish between active
infection or past exposure to infection and, therefore,
is not a conclusive indicator of active
gastrointestinal colonization by H.
pylori.
Principle of the BreathTek™ UBT
for H. pylori
Description of the Pranactin-Citric™ Diagnostic Drug
Component
The diagnostic drug component of the kit is 13C-urea,
a synthetic urea contained in a granulated powder (Pranactin-Citric™)
for reconstitution with potable water to provide a clear
solution for oral administration. The carbon in
the drug component is predominantly Carbon-13, a stable,
naturally occurring, non-radioactive isotope of carbon;
the relative abundance of Carbon-13 is greater than or
equal to 99%.
Each three (3) gram dose of Pranactin-Citric™ is supplied
in a polyethylene-lined foil pouch and contains 75 mg
of 13C-Urea, citric acid9, aspartame
and mannitol.
13C-urea is the diamide of 13C-carbonic
acid and is highly soluble in water (1 gram per mL at
25°C). It has the following chemical formula: 13CH4N2O.
An average adult body normally contains about 9.0 grams
of urea which is a product of protein metabolism.
Urea in the body is referred to as natural isotopic abundance
urea since it is composed of 98.9% 12C-urea
and 1.1% 13C-urea.
Principle of the Test
In the BreathTek™ UBT for H. pylori,
3 g of reconstituted Pranactin-Citric™ containing 75 mg
of 13C-urea is ingested by the patient.
In the presence of urease associated with gastric
H. pylori, 13C-urea is decomposed to
13CO2 and NH4+
according to the following equation:
(NH2)213CO + H2O
+ 2H+ > 13CO2
+ 2NH4
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-Citric™
solution was consumed.
Analysis of the breath samples is performed by Gas Isotope
Ratio Mass Spectrometry ("GIRMS") at qualified
laboratories licensed by Meretek
Diagnostics, Inc.
The BreathTek™ UBT can detect very low levels of H.
pylori colonization and, by assessing the entire
gastric mucosa, avoids the risk of sampling errors inherent
in biopsy based methods. In the absence of gastric
H. pylori,
the 13C-urea does not produce 13CO2
in the stomach. The ratio of 13CO2
to 12CO2 in the TEST breath sample
remains essentially the same as the BASELINE.
Warnings and Precautions
1. For in
vitro diagnostic use only. The Pranactin-Citric™
drug solution is taken orally as part of the diagnostic
procedure.
2. Phenylketonurics: Contains Phenylalanine,
75 mg per dosage unit.(For reference, 12 ounces of typical
diet cola soft drinks contain approximately 80 mg of
phenylalanine).
3. A negative result does not rule out the
possibility of Helicobacter pylori
infection. False negative results do occur with this
procedure. If clinical signs are suggestive of H.
pylori infection, retest with a new sample or
an alternate method.
4. Antimicrobials, proton pump inhibitors,
and bismuth preparations are known to suppress H.
pylori and ingestion of these within two weeks
prior to performing the BreathTek™ UBT may give false
negative results.
5. A false positive test may occur due to
urease associated with other gastric spiral organisms
observed in humans such as Helicobacter
heilmannii.
6. Premature TEST breath collection
time can lead to a false negative diagnosis for a patient
with a marginally positive BreathTek™ UBT.
7. A false positive test could occur
in patients who have achlorhydria.7
8. If particulate matter is visible in the
reconstituted Pranactin-Citric™ solution after thorough
mixing, the solution should not be used.
Patient Preparation
1. Remind the patient
that Pranactin-Citric™ contains phenylalanine.
Phenylketonurics restrict dietary phenylalanine.
2. The patient should
have fasted at least one hour before administering the
BreathTek™ UBT.
3. The patient should not have taken antimicrobials,
proton pump inhibitors, or bismuth preparations within
two weeks prior to administering the BreathTek™ UBT.
Limitations of the Test
1. The BreathTek™
UBT should not be used until four weeks or more after
the end of treatment for the eradication of H.
pylori, as earlier post-treatment assessment
may give false negative results.
2. The performance
characteristics for persons under the age of 18 have
not been established for this test.
3. The specimen integrity due
to storage of breath samples in collection tubes under
ambient conditions has not been determined beyond 20
days.
4. A correlation between
the number of H. pylori
organisms in the stomach and the BreathTek™ UBT result
has not been established.
5. The predicate device
(Meretek UBT®) was standardized in asymptomatic healthy
volunteers and subsequently validated in clinical trials
limited to patients with documented duodenal ulcer disease.
Bibliography
1. Marshall, B.J.,
Warren, J.R. Unidentified curved
bacilli on gastric epithelium in active chronic gastritis,
Lancet, June 4: 1273-1275; 1983.
2. Northfield T.C.,
Mendall M., Goggin P.M., (Eds), Helicobacter
pylori Infection. Pathophysiology, Epidemiology
and Management, Kluwer Academic Publisher (1993).
3. Rathbone B.J.,
Heatley R.V., (Eds) Helicobacter
pylori and Gastroduodenal Disease, Blackwell
Scientific Publicatons, 2nd Edition (1992).
4. Helicobacter
pylori in Peptic Ulcer Diseases,
Program and Abstracts. NIH Consensus Development
Conference, February 7-9, 1994, Bethesda, MD.
5. NIH Consensus
Development Panel, H.
pylori in Peptic Ulcer Disease, JAMA,
July 6, 1994 - Vol. 272, No. 1, 65-69.
6. Reference 2, page
113.
7. Borriello, S.P.,
Reed, P.J., Dolby, J.M., Barclay, F.E. and Webster,
A.D.B. Microbial and metabolic
profile of achlorhydric stomach: comparison of
pernicious anaemia and hypogammaglobulinaemia.
J. Clin. Pathol. 38, 946-953; 1985.
8. FDA, Center for
Drug Evaluation and Research, Division of Anti-Infective
Drug Products, DAIDP Points
to consider document - Helicobacter
pylori-associated Peptic Ulcer Disease.
Indication # 25. (March 1995 Addendum to March 15, 1995
Draft)
9. Graham, D.Y.,
Runke, D., Anderson, S., Malaty, H.M., and Klein, P.D.
Citric Acid as the Test Meal for
the 13C-Urea Breath Test. American
Journal of Gastroenterology, 5, 1214-1217; 1999.
For full prescribing information, review product labeling.
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