Duplicate Breath Testing To Confirm Eradication of H pylori
Duplicate Breath Testing To Confirm Eradication of H pylori
Background. Current standards for establishing a cure of H. pylori infection require two breath tests taken at least 4 weeks apart, to be negative.
Aim. To determine the incremental cost and accuracy of repeating a urea breath test (UBT) in clinical practice.
Methods. We identified 419 patients with documented Helicobacter pylori infection who received eradication therapy and then had two breath tests, one 4 weeks and the second at least 8 weeks after the completion of treatment. H. pylori infection was documented at baseline by a positive rapid urease test and histology.
Results. In patients with successful eradication of H. pylori infection (n = 317), the mean ± standard deviation delta over baseline (DOB) value before treatment was 43 ± 29 ppm. Following treatment, the mean DOB in cured was 0.56 ± 2.1 ppm at 1 month and was similar to the value obtained at the second breath (0.68 ± 1; P = 0.39), which was performed 60 ± 71 days after the first UBT. In patients remaining infected (n = 102), the mean DOB at baseline was 47 ± 20 ppm. Four weeks after treatment, the DOB was 40 ± 32 ppm. The second UBT was performed 94 ± 72 days after the first and the DOB was significantly greater than the first (47 ± 28; P = 0.040). There was no discordant result between the first breath test and second breath test. At a cost of 30 euros/breath test, the incremental cost of a second breath test was 12 570 euros in this cohort with no incremental clinical benefit.
Conclusions. A single UBT, 4 weeks after treatment is as effective as two serial breath tests in confirming H. pylori eradication. The incremental cost of the second breath test is very high with no incremental clinical benefit.
Testing for eradication of Helicobacter pylori is an important aspect of clinical trial design and is of critical importance in the evaluation of new therapies for H. pylori. Current guidance for new treatments seeking regulatory approval requires multiple tests obtained at one point of time to demonstrate eradication or a single test that is negative at different time points, usually a C urea breath test (UBT) obtained 4 weeks after completion of eradication therapy, which is negative 8 weeks or longer after completion of treatment. The European H. pylori study group has recommended that the UBT test may be used to confirm eradication 4 weeks after completion of treatment, but recommends that the UBT should be repeated at least 4 weeks after the first breath test and should remain negative for the patient to be considered as cured of H. pylori infection. Some regulatory agencies have based their criteria for successful eradication upon the recommendations of the European H. pylori study group. Health Canada, for example, accepts two negative UBTs performed 8 weeks apart as evidence for a cure of H. pylori infection in regulatory trials. Published guidance from the US Food and Drug administration states that patients will be considered non-evaluable at the time that cure is being assessed if only one test is available and that test is negative. If two different endoscopic tests are available at the test-of-cure time point and these two tests are negative, infection in those patients is considered eradicated. As a result, two different trial designs have been used in the US: (i) a one time-point assessment of eradication using a combination of endoscopic tests a minimum of 4 weeks after completion of eradication therapy, e.g. rapid urease test and histology; and (ii) a single test utilized at two time points, e.g. serial breath testing with the tests obtained a minimum of 4 weeks apart.
The likely reason for these recommendations is that regulatory agencies are concerned about the problem of recrudescence of H. pylori. Recrudescence is said to occur when H. pylori is suppressed, but not eradicated by treatment and becomes undetectable 4 weeks after treatment. Weeks or months later, the organism recovers from the inhibition induced by the anti-microbials, multiplies and becomes detectable once again. Another group of patients that is of concern is the group of patients that has delta over baseline (DOB) values that lie between 2 and 5 ppm on the first post-treatment UBT. Some studies have suggested that patients with these intermediate values are more likely to be those who develop a positive UBT at a later time-point. The aim of this study was to determine the diagnostic yield and the incremental cost of the second breath test.
Background. Current standards for establishing a cure of H. pylori infection require two breath tests taken at least 4 weeks apart, to be negative.
Aim. To determine the incremental cost and accuracy of repeating a urea breath test (UBT) in clinical practice.
Methods. We identified 419 patients with documented Helicobacter pylori infection who received eradication therapy and then had two breath tests, one 4 weeks and the second at least 8 weeks after the completion of treatment. H. pylori infection was documented at baseline by a positive rapid urease test and histology.
Results. In patients with successful eradication of H. pylori infection (n = 317), the mean ± standard deviation delta over baseline (DOB) value before treatment was 43 ± 29 ppm. Following treatment, the mean DOB in cured was 0.56 ± 2.1 ppm at 1 month and was similar to the value obtained at the second breath (0.68 ± 1; P = 0.39), which was performed 60 ± 71 days after the first UBT. In patients remaining infected (n = 102), the mean DOB at baseline was 47 ± 20 ppm. Four weeks after treatment, the DOB was 40 ± 32 ppm. The second UBT was performed 94 ± 72 days after the first and the DOB was significantly greater than the first (47 ± 28; P = 0.040). There was no discordant result between the first breath test and second breath test. At a cost of 30 euros/breath test, the incremental cost of a second breath test was 12 570 euros in this cohort with no incremental clinical benefit.
Conclusions. A single UBT, 4 weeks after treatment is as effective as two serial breath tests in confirming H. pylori eradication. The incremental cost of the second breath test is very high with no incremental clinical benefit.
Testing for eradication of Helicobacter pylori is an important aspect of clinical trial design and is of critical importance in the evaluation of new therapies for H. pylori. Current guidance for new treatments seeking regulatory approval requires multiple tests obtained at one point of time to demonstrate eradication or a single test that is negative at different time points, usually a C urea breath test (UBT) obtained 4 weeks after completion of eradication therapy, which is negative 8 weeks or longer after completion of treatment. The European H. pylori study group has recommended that the UBT test may be used to confirm eradication 4 weeks after completion of treatment, but recommends that the UBT should be repeated at least 4 weeks after the first breath test and should remain negative for the patient to be considered as cured of H. pylori infection. Some regulatory agencies have based their criteria for successful eradication upon the recommendations of the European H. pylori study group. Health Canada, for example, accepts two negative UBTs performed 8 weeks apart as evidence for a cure of H. pylori infection in regulatory trials. Published guidance from the US Food and Drug administration states that patients will be considered non-evaluable at the time that cure is being assessed if only one test is available and that test is negative. If two different endoscopic tests are available at the test-of-cure time point and these two tests are negative, infection in those patients is considered eradicated. As a result, two different trial designs have been used in the US: (i) a one time-point assessment of eradication using a combination of endoscopic tests a minimum of 4 weeks after completion of eradication therapy, e.g. rapid urease test and histology; and (ii) a single test utilized at two time points, e.g. serial breath testing with the tests obtained a minimum of 4 weeks apart.
The likely reason for these recommendations is that regulatory agencies are concerned about the problem of recrudescence of H. pylori. Recrudescence is said to occur when H. pylori is suppressed, but not eradicated by treatment and becomes undetectable 4 weeks after treatment. Weeks or months later, the organism recovers from the inhibition induced by the anti-microbials, multiplies and becomes detectable once again. Another group of patients that is of concern is the group of patients that has delta over baseline (DOB) values that lie between 2 and 5 ppm on the first post-treatment UBT. Some studies have suggested that patients with these intermediate values are more likely to be those who develop a positive UBT at a later time-point. The aim of this study was to determine the diagnostic yield and the incremental cost of the second breath test.
Source...