HELICOBACTER Powder for oral solution Ref.[8561] Active ingredients: Urea ¹³C

This medicinal product should be administered by a healthcare professional and under appropriate medical supervision.

Posology

Helicobacter Test INFAI is a breath test for single administration. Patients from the age of 12 must take the contents of 1 jar with 75 mg.

Method of administration

For performance of the test, 200 ml 100% orange juice or 1 g citric acid in 200 ml water for patients from the age of 12 and older (as a pre-administered test meal), as well as tap water (for dissolving the ¹³C-urea powder) are necessary.

The patient must have fasted for over 6 hours, preferably overnight. The test procedure takes approximately 40 minutes.

In case it is necessary to repeat the test procedure, this should not be done until the following day.

The suppression of Helicobacter pylori might give false negative results. Therefore the test shall be used after at least four weeks without systemic antibacterial therapy and two weeks after last dose of acid antisecretory agents. Both might interfere with the Helicobacter pylori status. This is especially important after Helicobacter eradication therapy.

It is important to follow the instructions for use adequately (see section 6.6), otherwise the reliability of the outcome will become questionable.

Due to the fact that only 75 mg of ¹³C-urea is delivered, an overdose is not expected.

3 years.

Do not store above 25°C.

A test set contains the following parts:

1. The test is to be performed in the presence of a qualified person.

2. Each patient should be documented according to the provided data sheet. It is recommended to perform the test with the patient being in a resting position.

3. The test starts with the collection of samples for the determination of baseline-value (00-minute-value):

• Take the straw and the two sample tubes with the label “Sampling time: 00-minute-value” out of the test set.
• Remove the stopper from one of the sample tubes, unwrap the straw and place the straw into the container.
• Now the patient breathes gently through the straw until the inner surface of the sample tube steams up.
• By continuously breathing the patient must pull out the straw and immediately close the sample tube with its stopper. (If the sample tube remains open for more than 30 seconds, the test result might be falsified.)
• Hold the sample tube upright and stick the bar-code label marked “00-minute-value” round the sample tube, so that the lines of the bar-code are horizontal.

4. Fill up the second sample tube (Label “Sampling time: 00-minute-value”) with breath by following the same procedure.

5. Now 200 ml of 100 % orange juice or 1 g citric acid in 200 ml water must be drunk by the patient without delay.

6. Now the preparation of the test solution follows:

• The jar labelled "¹³C-urea powder" is taken from the test set, opened, and filled up to three quarters of its volume with tap water.
• Close the jar and shake it carefully until all the powder is dissolved. Pour the contentsinto a drinking glass.
• Fill the ¹³C-urea jar to the brim with water for a second and third time and add these contents to the drinking glass (total volume of tap water should be approximately 30 ml).

7. This test solution must now be drunk immediately by the patient, and the time of application must be noted.

8. Thirty minutes after administration of the test solution (point 7), collect the 30-minute-value samples in the two containers which are left in the test package (Label “Sampling time: 30-minute-value”), as described under steps 3 to 4. Use the bar-code labels marked “30-minute-value” for these samples.

9. Put the relevant bar-code label on the data sheet for patient documentation. Finally seal the package with the sticker.

10. The sample tubes have to be sent in the original packaging, for analysis, to a qualified laboratory.

Analysis of breath samples and testing specification for laboratories

The breath samples, collected in 10 ml glass- or plastic sample tubes, are analysed by isotope ratio mass spectrometry (IRMS).

The analysis of the ¹³C/¹²C-ratio in carbon dioxide of breath is an integrated part of the diagnostic test Helicobacter Test INFAI. The accuracy of the test strongly depends on the quality of the breath analysis. The specification of breath analysis parameters like linearity, stability (reference gas precision), and precision of measurement are fundamental for the accuracy of the system.

It has to be ensured that the analysis is carried out by a qualified laboratory. The method validated in the application is as follows:

Sample preparation for (IRMS)

To determine the ¹³C/¹²C-ratio of carbon dioxide in breath by mass spectrometric analysis the carbon dioxide must be separated from the breath and introduced into the mass spectrometer. The automatic preparation system for isotope mass spectrometers which is dedicated for breath test analysis is based on a gas-chromatographic continuous flow separation technique.

Water is removed from the sample by means of a Nafion water trap or the gas-chromatographic preparation system that separates the individual gases in a gas chromatographic column with Helium as eluent. Passing the column the separated gas species of breath are detected by an ionisation detector. The fraction of carbon dioxide gas, identified by its characteristic retention time, is introduced into mass spectrometer.

Mass spectrometric analysis

To analyse the separated carbon dioxide sample gas its molecules must be ionised, formed into a beam, accelerated by an electric field, deflected in a magnetic field, and finally detected. These five processes take place in the analyser of a mass spectrometer, which consists of three separate sections: the source, flight tube, and collector. Ionisation, beam formation and acceleration all occur in the source, magnetic deflection takes place in the flight tube and detection takes place in the collector.

Sample inlet

For introduction of the carbon dioxide into the analyser many sample inlet systems are available. For breath test analysis the individual balancing of the carbon dioxide of the sample to a reference standard gas is essential. This ensures the high accuracy of this system, as calculation of the isotopic content in carbon dioxide is done with respect to an independent standard.

Specifications for determining ¹³C/¹²C-ratios

The breath test concept relies on the administration of a specifically ¹³C-labelled urea whose metabolite utilisation is monitored by measuring ¹³CO₂ in the expired breath gas.

The mass spectrometer must be capable of:

Multiple replicate analyses: Minimum of 3 replicate analyses of the same sample during operation

Security access: Storing of operating parameters and of results under security access to avoid later manipulation

Adjustment: ¹³C / ¹²C-ratio with respect to Pee Dee Beliminate (PDB)

Sample loop: <200 μl

The principal tests to verify the specifications are linearity, stability (reference gas precision), and precision of measurement.

All mass spectrometers for breath analysis must comply with the following specifications:

Linearity: ≤0.5‰ for breath samples varying between 1% and 7% CO₂-concentration

Stability: ≤0.2‰ on 10 consecutive pulses

Precision of measurement: ≤0.3‰ for ¹³C at natural abundance using a 10 ml breath sample tube with 3% CO₂ breath concentration

Helicobacter pylori infection is present if the difference in ¹³C/¹²C of baseline-value and 30-minute-value exceeds 4.0‰.

Alternatively, any other suitable-validated method may be used, carried out by any objectively qualified laboratory.