A randomized trial of lansoprazole, amoxycillin, and clarithromycin versus lansoprazole, bismuth, metronidazole and tetracycline in the retreatment of patients failing initial Helicobacter pylori therapy.

BACKGROUND/AIM: 10-30% of the patients treated for Helicobacter pylori fail to clear the infection after initial therapy. Little is known as to the efficacy of retreatment regimens in these patients. Proton pump inhibitor (PPI) -based triple and quadruple therapies demonstrate efficacies of 80-90% as initial therapy for H. pylori infection, but whether these regimens are as effective when used for retreatment is unknown. The efficacy of a metronidazole-containing regimen in this situation is also unknown. Our aim was to compare the efficacy of a nonmetronidazole-containing PPI-based triple versus a PPI-based quadruple therapy containing metronidazole in patients failing previous H. pylori therapy. METHODS: 48 patients were enrolled in this study at two sites after failure of previous H. pylori therapy as determined by a positive (14)C-urea breath test. Patients were stratified by prior treatment with a metronidazole-containing regimen and were then randomized to either lansoprazole (L) 30 mg twice daily, amoxycillin (A) 1,000 mg twice daily, and clarithromycin (C) 500 mg twice daily for 14 days (LAC) or L 30 mg four times daily, bismuth subsalicylate (B) 2 tablets four times daily, metronidazole (M) 250 mg four times daily and tetracycline (T) 250 mg four times daily for 14 days (LBMT). Side effects and compliance (pill count) were assessed at the completion of therapy. A repeat (14)C-urea breath test was performed 4 or more weeks after completion of therapy, and cure was defined as a negative test result. RESULTS: 48 patients (16 males and 32 females) were enrolled in this study. 20 patients received LAC (18 prior M), and 28 received LBMT (23 prior M). Per protocol and intention-to-treat efficacies were 82% (95% CI 64-100%) and 75% (95% CI 56-94%) for LAC and 80% (96% CI 64-96%) and 71% (95% CI 54-88%) for LBMT (p = 0.85 per protocol and p = 0.78 intention to treat between LAC and LBMT), respectively. The compliance (> or =80% of pills taken) was found to be 89% in both treatment groups. Side effects were noted in 84% for LAC and in 82% for LBMT, but were mild and did not cause discontinuation of therapy. CONCLUSIONS: PPI-based triple and quadruple therapy with both LAC and LBMT are effective in retreating patients failing initial metronidazole-based H. pylori therapies. LAC was not statistically superior to LBMT as a 'retreatment' regimen in this clinical situation, but the small sample size and wide confidence limits do not preclude the possibility of a smaller but significant difference in efficacy between the regimens. To determine whether LAC or LBMT is as effective for retreating patients failing non-metronidazole-containing regimens requires further study.

Outcomes of Helicobacter pylori treatment in community practice and impact of therapeutic effectiveness information on physician behaviour.

BACKGROUND: The effect of knowledge of Helicobacter pylori eradication rates on physician choice of treatment regimen is unknown. As practice variation results in differences in outcome, it is important to determine whether physician behaviour can be altered by such knowledge. AIMS: (i) To determine whether dissemination of practice variation and effectiveness data regarding H. pylori changes subsequent prescribing behaviour and (ii) whether this change results in an improvement in the effectiveness of therapy. METHODS: Community gastroenterologists in the Portland metropolitan area enrolled patients being treated for H. pylori. The regimen used, diagnostic method, indication and success in eradication was measured. Patient-centred factors were also measured, including symptoms, interest in post-treatment diagnostic testing and willingness to pay. RESULTS: Significantly more physicians participating in both studies used proton pump inhibitor-triple therapy based regimens in this trial (46% vs. 85%, P=0.01), although the overall difference between the two trials was not significant (62% vs. 83%, P=0.11). There was no change in overall eradication rates by per protocol analysis between trials (84% vs. 85%, P=0.78), but a significant decrease in effectiveness by intention-to-treat analysis observed in this study (80% vs. 71%, P=0.03). Significantly more patients were treated for reasons other than peptic ulcer disease in this study (P=0.0003). CONCLUSIONS: The overall effectiveness of H. pylori therapy in practice remains good. There has been a shift in the choice of treatment regimen and indication for therapy between the time periods of the two studies. Dissemination of treatment data appears to effect prescribing behaviour, but whether it has a beneficial effect on treatment outcome remains unproven.

Cytological screening for Barrett's esophagus using a prototype flexible mesh catheter.

The current cost of endoscopically screening patients with gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) is considerable. A nonendoscopic device that allows for screening of these patients would offer significant cost savings. This pilot study evaluates the utility of cytologically diagnosing BE using a prototype flexible mesh catheter. Patients with known BE undergoing indicated surveillance endoscopy were enrolled in the study. Cytology specimens were obtained using a prototype flexible catheter and were evaluated for the presence of glandular cells, goblet cells, squamous cells, inflammation, and dysplasia. Eleven patients with BE were enrolled in the study. None of the patients experienced complications. Specimens from eight patients (73%) were adequate for evaluation and seven of these patients (87.5%) had goblet cells diagnostic for BE. In conclusion, flexible mesh catheters potentially offer a sensitive, inexpensive, and minimally invasive approach to evaluating patients with GERD and BE.

Noninvasive tests as a substitute for histology in the diagnosis of Helicobacter pylori infection.

BACKGROUND: Rapid urease tests for Helicobacter pylori have a sensitivity of 80% to 90%. Therefore histologic examination of gastric biopsies is recommended as a "backup" diagnostic test in rapid urease test-negative patients. However, noninvasive tests (urea breath test, serology, whole blood antibody tests) may provide a more rapid diagnosis and be less expensive but offer similar accuracy. METHODS: Sixty-seven patients (no prior treatment for H pylori, no proton pump inhibitors, antibiotics, or bismuth within 4 weeks) undergoing endoscopy for evaluation of dyspepsia symptoms and testing rapid urease test-negative by antral biopsy were enrolled. All had the following tests: gastric biopsies (2 antral, 1 fundus; H&E and Alcian Yellow stain) examined for gastritis and H pylori; (13)C-UBT; capillary blood for whole blood rapid antibody tests: FlexSure HP, QuickVue, AccuStat, and Stat-Simple Pylori; serum for FlexSure HP; HM-CAP enzyme-linked immunoassay. H pylori infection was diagnosed (reference standard) if chronic gastritis was present on histology and at least 2 of the 3 following tests were positive: urea breath test, H pylori organisms unequivocally demonstrated in biopsies on special stain, and/or enzyme-linked immunoassay. The test and treatment costs per patient were calculated. RESULTS: Of 67 patients with a negative rapid urease test, 4 were positive for H pylori. None had active peptic ulcer disease. Histology only identified 1 patient with organisms visible on special stain. Using chronic active gastritis (neutrophilic and mononuclear infiltrate) as a diagnostic criterion for H pylori, 6 patients would have been judged positive. However, only 2 of these were truly positive by the reference standard (positive predictive value 33%). Negative predictive value for presence of organisms and chronic active gastritis was 95% and 97%, respectively. All of the noninvasive tests identified all 4 truly positive patients correctly. Urea breath test and FlexSure whole blood assay yielded a substantial number of false-positive results (positive predictive value 31% and 36%, respectively); positive predictive value for the other tests ranged from 50% to 80%. All tests except histology had a negative predictive value of 100%. Histology was the most costly test (p < 0. 001 compared with all other tests), followed by urea breath test and HM-CAP serology (p < 0.001 compared with all rapid antibody tests). CONCLUSIONS: Whole blood or serum antibody testing is a rapid, accurate, and cost-effective means for establishing H pylori status in rapid urease test-negative patients. Whole blood or serology rapid antibody testing should substitute for histology when the patient has not been previously treated for H pylori.

Evaluation of rapid antibody tests for the diagnosis of Helicobacter pylori infection.

OBJECTIVE: The aim of this study was to compare the performance characteristics of one serum and four whole blood rapid antibody tests for Helicobacter pylori infection. METHODS: A total of 97 outpatients referred for endoscopic evaluation of dyspepsia were included. Antral biopsies were obtained for histology and rapid urease test. Serum was tested with an enzyme-linked immunoassay (HM-CAP) and a rapid serology test (FlexSure HP). A commercially available 13C-urea breath test was performed. Capillary blood obtained by fingerstick was tested with FlexSure HP, QuickVue, Accustat, and StatSimple pylori tests. Sensitivity, specificity, and accuracy of each rapid test was calculated relative to a criterion standard of histological gastritis and at least two of the four following tests positive: identifiable organisms on specially stained slides, rapid urease test, urea breath test, or serum immunoassay. RESULTS: A total of 30 patients (31%) were infected. The FlexSure HP Serum, and FlexSure HP, QuickVue, Accustat, and StatSimple pylori whole blood tests had sensitivities of 90%, 87%, 83%, 76%, and 90%; specificities of 94%, 90%, 96%, 96%, and 98%, and accuracies of 93%, 88%, 92%, 87%, and 96%, respectively. Sensitivities were not statistically different. StatSimple pylori was more specific than FlexSure HP whole blood (p<0.03), and more accurate than FlexSure whole blood (p<0.024) and Accustat (p< 0.01). Serum immunoassay was significantly more sensitive (97%) than FlexSure whole blood, QuickVue, and Accustat (p<0.01), but its specificity (95%) was not statistically different from the rapid tests. CONCLUSION: Rapid antibody testing provides an accurate diagnosis of H. pylori infection. In general, these tests are less sensitive than, but as specific as, standard serology.

Effectiveness of Helicobacter pylori therapies in a clinical practice setting.

BACKGROUND: Whether eradication rates for Helicobacter pylori treatment regimens obtained in controlled clinical trials (efficacy) can also be obtained in clinical practice (effectiveness) is unknown because no such trials have been reported in the United States. OBJECTIVES: To determine the eradication rates of H pylori in a community practice setting and the effects of practice variation in the choice of treatment regimen on patient outcome (H pylori infection cure) and cost. METHODS: Between February 1 and December 30, 1996, 38 community-based gastroenterologists in the Portland, Ore, metropolitan area enrolled a total of 250 patients infected with H pylori, as determined by endoscopic or noninvasive methods. Various therapeutic regimens aimed at eradicating H pylori were used by the gastroenterologists, and a posttreatment urea breath test was used to determine H pylori infection cure. Compliance and incidental effects were also measured and decision analysis was used to estimate the cost of treatment. RESULTS: The regimens used varied considerably. Patients receiving a 2- or 3-times-a-day treatment regimen were significantly more compliant (P=.01) than those receiving a 4-times-a-day regimen. Proton pump inhibitor-based triple-therapy regimens were significantly more effective than all other treatment regimens combined (87% vs 70%; P = .001) in eradicating H pylori. These proton pump inhibitor-based triple-therapy regimens were also more cost-effective by decision analysis for a hypothetical cohort of patients with duodenal ulcer disease. CONCLUSIONS: The considerable variation in the choice of treatment regimens affects the clinical and economic outcomes of patients undergoing therapy for H pylori infection. Whether these data reflect the outcome in other communities is unknown but should be determined. It will be necessary to determine if the dissemination of these data results in a reduction of practice variation and improvement in clinical and economic outcomes of patients being treated for H pylori infection in clinical practice.