Rifabutin in Patients With 3 H. Pylori Eradication Failures
Rifabutin in Patients With 3 H. Pylori Eradication Failures
This was a prospective multicentre study involving nine Spanish hospitals, including consecutive patients for whom the following three treatments had consecutively failed to eradicate H. pylori infection: first treatment with a PPI, clarithromycin and amoxicillin; second treatment with a quadruple regimen with a PPI, bismuth, tetracycline and metronidazole; and third treatment with a PPI, amoxicillin and levofloxacin. H. pylori eradication failure with first-, second-, and third-line regimens was defined by a positive C-urea breath test 4–8 weeks after completion of treatment. The exclusion criteria were as follows: (i) age under 18 years, (ii) presence of clinically significant associated conditions (neoplastic diseases, coagulation disorders, and hepatic, cardiorespiratory, or renal diseases), (iii) previous gastric surgery and (iv) allergy to any of drugs used in the study. The protocol was approved by the local ethics committee, and informed consent was obtained from all the patients.
A fourth eradication regimen with rifabutin (150 mg b.d.), amoxicillin (1 g b.d.) and a PPI (standard dose b.d.) was prescribed for 10 days. All drugs were administered together after breakfast and dinner. Patients were informed of potential side effects (mainly metallic taste, nausea, and diarrhoea) during the treatment period. Compliance with therapy was defined as intake of 100% of the medication prescribed and was determined by a questionnaire and recovery of empty medication envelopes (both performed by the same gastroenterology responsible for treating the patient). The incidence of adverse effects was evaluated using a specific questionnaire. Adverse effects were classified as mild, moderate, or severe depending on the intensity.
Eradication of H. pylori was defined by a negative C-urea breath test result (with citric acid and 100 mg of urea, using a previously reported protocol) performed 4–8 weeks after completion of re-treatment. The test was carried out by nurses who were unaware of the therapy administered and the patients' H. pylori status. As endoscopy – and consequent culture – was not performed after therapy, antibiotic susceptibility was unknown and, as such, the eradication regimen was chosen empirically.
As leucopenia and trombocytopenia have been reported after treatment with rifabutin, serum samples were obtained in all patients before and after completing treatment to exclude myelotoxicity.
The 95% CI was calculated for categorical variables and the mean ± standard deviation for quantitative variables. Analysis of the efficacy of H. pylori eradication was performed on an intention-to-treat basis (including all eligible patients enrolled in the study regardless of compliance with the study protocol; patients with unevaluable data were assumed to have been unsuccessfully treated) and on a per-protocol basis (excluding patients whose compliance with therapy was poor and patients with unevaluable data after therapy). Sample size was predetermined taking the following parameters into consideration: epsilon = ±10%; p1 (initial estimate) of efficacy of H. pylori treatment = 50%; confidence level = 0.95%. A sample size of 97 patients was necessary. As the probability of loss to follow-up was estimated at around 5%, the final size of the sample was approximately 100 patients.
Patients and Methods
Patients
This was a prospective multicentre study involving nine Spanish hospitals, including consecutive patients for whom the following three treatments had consecutively failed to eradicate H. pylori infection: first treatment with a PPI, clarithromycin and amoxicillin; second treatment with a quadruple regimen with a PPI, bismuth, tetracycline and metronidazole; and third treatment with a PPI, amoxicillin and levofloxacin. H. pylori eradication failure with first-, second-, and third-line regimens was defined by a positive C-urea breath test 4–8 weeks after completion of treatment. The exclusion criteria were as follows: (i) age under 18 years, (ii) presence of clinically significant associated conditions (neoplastic diseases, coagulation disorders, and hepatic, cardiorespiratory, or renal diseases), (iii) previous gastric surgery and (iv) allergy to any of drugs used in the study. The protocol was approved by the local ethics committee, and informed consent was obtained from all the patients.
Therapy
A fourth eradication regimen with rifabutin (150 mg b.d.), amoxicillin (1 g b.d.) and a PPI (standard dose b.d.) was prescribed for 10 days. All drugs were administered together after breakfast and dinner. Patients were informed of potential side effects (mainly metallic taste, nausea, and diarrhoea) during the treatment period. Compliance with therapy was defined as intake of 100% of the medication prescribed and was determined by a questionnaire and recovery of empty medication envelopes (both performed by the same gastroenterology responsible for treating the patient). The incidence of adverse effects was evaluated using a specific questionnaire. Adverse effects were classified as mild, moderate, or severe depending on the intensity.
Diagnostic Methods to Confirm Eradication
Eradication of H. pylori was defined by a negative C-urea breath test result (with citric acid and 100 mg of urea, using a previously reported protocol) performed 4–8 weeks after completion of re-treatment. The test was carried out by nurses who were unaware of the therapy administered and the patients' H. pylori status. As endoscopy – and consequent culture – was not performed after therapy, antibiotic susceptibility was unknown and, as such, the eradication regimen was chosen empirically.
Analytical Control
As leucopenia and trombocytopenia have been reported after treatment with rifabutin, serum samples were obtained in all patients before and after completing treatment to exclude myelotoxicity.
Statistical Analysis
The 95% CI was calculated for categorical variables and the mean ± standard deviation for quantitative variables. Analysis of the efficacy of H. pylori eradication was performed on an intention-to-treat basis (including all eligible patients enrolled in the study regardless of compliance with the study protocol; patients with unevaluable data were assumed to have been unsuccessfully treated) and on a per-protocol basis (excluding patients whose compliance with therapy was poor and patients with unevaluable data after therapy). Sample size was predetermined taking the following parameters into consideration: epsilon = ±10%; p1 (initial estimate) of efficacy of H. pylori treatment = 50%; confidence level = 0.95%. A sample size of 97 patients was necessary. As the probability of loss to follow-up was estimated at around 5%, the final size of the sample was approximately 100 patients.
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