Sequential Helicobacter pylori eradication therapy in Myanmar; a randomized clinical trial of efficacy and tolerability.

BACKGROUND AND AIM: There is little published research to examine the best approach to the management of Helicobacter pylori in Myanmar. This study aimed to determine the relative efficacy and tolerability of sequential eradication therapy compared to Myanmar's current recommendation of a concomitant four drug regimen. METHODS: Patients were screened for H. pylori using monoclonal Stool Antigen Testing (SAT). Those testing positive were randomized 1:1 to receive receive Myanmar's first-line regimen of 14 days of concomitant rabeprazole, clarithromycin, amoxycillin and tinidazole (140 pills, cost US$23) or 10 days of sequential rabeprazole, clarithromycin, amoxycillin and tinidazole (60 pills, cost US$10). Adherence and adverse effects were recorded, and the efficacy of the regimens assessed with repeat SAT. RESULTS: Of the 1011 patients screened for H. pylori infection, 313 (31%) tested positive. There was no statistical difference in the cure rates of the two regimens in either intention-to-treat: 128/157 (82%; 95% confidence interval (CI): 75-87%) receiving sequential therapy versus 123/156 (79%; 95% CI: 72-85%) receiving concomitant therapy (P = 0.55) or per-protocol analysis: 125/131 (95%; 95% CI: 90-98) receiving sequential therapy versus 121/130 (93%; 95% CI: 87-96) receiving concomitant therapy (P = 0.42). Side effects of therapy were reported in 54/157 (47%) patients taking sequential therapy compared with 62/156 (53%) taking concomitant therapy, but this difference did not reach statistical significance (P = 0.33). CONCLUSIONS: In this high-burden, resource-poor setting, less expensive sequential therapy was as effective and as well tolerated as the currently recommended concomitant four drug regimen for eradication of H. pylori.

Clinical trial: knowledge of negative Helicobacter pylori status reduces subsequent dyspepsia-related resource use.

BACKGROUND: Screening for Helicobacter pylori reduces dyspepsia and dyspepsia-related costs in positive individuals. AIMS: To assess effect of knowledge of H. pylori status on healthcare-seeking in negative individuals. METHODS: H. pylori-negative subjects in a community screening programme were randomized to placebo triple therapy or informed of their negative H. pylori status. Dyspepsia-related resource data were extracted from primary care records at 2 years, and National Health Service reference costs were applied to calculate the total cost per subject. Proportions of individuals incurring any cost were compared using a relative risk (RR) and 95% confidence interval (CI). Differences in costs were compared using an independent sample t-test. RESULTS: A total of 1353 H. pylori-negative individuals were randomized to placebo whilst 1355 were informed of their infection status. In the placebo arm, 212 (16%) subsequently incurred any dyspepsia-related cost compared to 172 (13%) informed of their infection status (RR of incurring cost = 0.81; 95% CI: 0.67-0.97). Those informed of their infection status incurred lower costs (mean saving per individual = pound 11.02; 95% CI: - pound 3.52 to 25.56). CONCLUSIONS: H. pylori-negative individuals informed of infection status sought health care for dyspepsia less often than those who were unaware. Population screening may reduce dyspepsia-related costs in uninfected, as well as infected individuals.

Tinidazole: a nitroimidazole antiprotozoal agent.

BACKGROUND: Tinidazole, a structural analogue of metrondazole, is an antiprotozoal agent that has been widely used in Europe and developing countries for >2 decades with established efficacy and acceptable tolerability. It was recently approved by the US Food and Drug Administration for the treatment of trichomoniasis, giardiasis, amebiasis, and amebic liver abscess. OBJECTIVE: This article reviews the pharmacologic and pharmacokinetic properties and clinical usefulness of tinidazole. METHODS: Relevant information was identified through a search of MEDLINE (1966-August 2005), Iowa Drug Information Service (1966-August 2005), and International Pharmaceutical Abstracts (1970-August 2005) using the terms tinidazole, Fasigyn, and nitroimidazole. RESULTS: In vitro, tinidazole exhibits activity against pathogenic protozoa (eg, Tricbomonas vaginalis, Entamoeba bistolytica, Giardia duodenalis), a wide range of clinically significant anaerobic bacteria (eg, Bacteroides fragilis, Clostridium difficile), and the microaerophilic bacterium Helicobacter pylori. In susceptible protozoal and bacterial cells, tinidazole is reduced to cytotoxic intermediates that covalently bind to DNA, causing irreversible damage. In human adults, tinidazole had a bioavailability of 100% and a V(d) of 50.7 L, was minimally bound to plasma protein (12%), had a plasma elimination t((1/2)) of 12.3 hours, and was eliminated primarily by hepatic metabolism (approximately 63%). Dose adjustment does not appear to be necessary on the basis of race, sex, or renal function. No data were found on the disposition of tinidazole in patients with hepatic insufficiency; therefore, use of tinidazole in patients with severe hepatic impairment (Child-Pugh class C) is not recommended. Clinical cure rates in patients with trichomoniasis, giardiasis, amebiasis, and amebic liver abscess were generally >90%. In comparative trials, tinidazole was as effective as metronidazole in the treatment of trichomoniasis and was significantly more effective than metronidazole in the treatment of giardiasis (P < 0.05) and amebiasis (P < 0.05). The most commonly reported (>1%) adverse effects included bitter taste, nausea, abdominal discomfort, anorexia, vomiting, and fatigue. The recommended dosage of tinidazole is a single dose of 2 g for trichomoniasis and giardiasis, and 2 g/d for 3 to 5 days for amebiasis. CONCLUSIONS: Tinidazole appears to be a promising agent for the treatment of trichomoniasis, giardiasis, amebiasis, and amebic liver abscess. Clinical studies are needed to evaluate the use of tinidazole against anaerobic bacteria and H pylori.

The prolongation of triple therapy for Helicobacter pylori does not allow reaching therapeutic outcome of sequential scheme: a prospective, randomised study.

BACKGROUND AND AIM: One-week triple therapy for Helicobacter pylori revealed, during these last few years, a decrease in the eradication rate, so that the prolongation of its duration has been proposed. A sequential scheme recently showed very satisfactory results. We performed a prospective randomised study with the aim of either evaluating whether the triple therapy prolongation may improve its effectiveness and comparing its outcome with that of sequential regimen. PATIENTS AND METHODS: Three hundred and forty-two H. pylori positive patients completed the study. They were randomised to receive one of the following treatments: (i) a 7-day triple therapy comprising of rabeprazole (20 mg, b.i.d.) plus clarithromycin (500 mg, b.i.d.) and amoxycillin (1 g, b.i.d.); (ii) a 10-day triple therapy comprising the same scheme; (iii) a 10-day sequential regimen comprising of rabeprazole (20 mg, b.i.d.) plus amoxycillin (1 g, b.i.d.) for 5 days followed by rabeprazole (20 mg, b.i.d.) plus clarithromycin (500 mg, b.i.d.) and tinidazole (500 mg, b.i.d.) for the next 5 days. Therapeutic results were expressed using both intention-to-treat and per protocol analyses with 95% confidence intervals. A model of multivariate logistic regression analysis was performed using therapeutic outcome as a dependent variable and including endoscopic finding, smoking habit, age and sex as candidates for the model. RESULTS: Sequential regimen showed a significant gain in the eradication rate as compared to the 7-day (P < 0.0001) and the 10-day (P < 0.01) triple therapies, respectively. Overall eradication was lower in smokers than in non-smokers, but the difference remained significant only in the 7-day triple therapy (P < 0.01). Additionally, the overall eradication was higher in peptic ulcer than dyspepsia (P < 0.01), even if this difference was significant only for both triple therapies. CONCLUSIONS: Seven-day triple therapy achieves disappointing eradication rates in dyspeptics and smokers. Prolonging triple therapy to 10 days does not significantly improve the eradication rate. The novel 10-day sequential regimen is more effective and equally tolerated than the 10-day triple therapy.

Sequential treatment for Helicobacter pylori eradication in duodenal ulcer patients: improving the cost of pharmacotherapy.

BACKGROUND: Several studies have shown that Helicobacter pylori eradication rates with standard 7-day triple therapy are unsatisfactory. A novel 10-day sequential treatment regimen recently achieved a significantly higher eradication rate. To improve the pharmacotherapeutic cost, we evaluated whether an acceptable eradication rate could be achieved in peptic ulcer patients by halving the dose of clarithromycin. METHODS: In a prospective, open-label study, 152 duodenal ulcer patients with H. pylori infection, assessed by rapid urease test and histology, were enrolled. Patients were randomized to receive either a 10-day sequential treatment comprising rabeprazole 20 mg b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by rabeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for the remaining 5 days (high-dose therapy), or a similar schedule with the clarithromycin doses halved to 250 mg b.d. (low-dose therapy). No further antisecretory drugs were offered. Four to six weeks after therapy, H. pylori eradication and ulcer healing rates were assessed by endoscopy. RESULTS: Similar H. pylori eradication rates were observed following high- and low-dose regimens for both per protocol (97.3% vs. 95.9%; P = N.S.) and intention-to-treat (94.7% vs. 92.2%; P = N.S.) analyses. No major side-effects were reported. At repeat endoscopy, peptic ulcer healing was observed in 93% and 93% of patients following high- and low-dose therapy, respectively. CONCLUSION: The cheaper low-dose sequential regimen may be suggested for H. pylori eradication in duodenal ulcer patients, even without continued proton pump inhibitor therapy after eradication treatment.

The cost-effectiveness of population Helicobacter pylori screening and treatment: a Markov model using economic data from a randomized controlled trial.

BACKGROUND: Economic models have suggested that population Helicobacter pylori screening and treatment may be a cost-effective method of reducing mortality from gastric cancer. These models are conservative as they do not consider that the programme may reduce health service peptic ulcer and other dyspepsia costs. We have evaluated the economic impact of population H. pylori screening and treatment over 2 years in a randomized controlled trial and have incorporated the results into an economic model exploring the impact of H. pylori eradication on peptic ulcer disease and gastric cancer. METHODS: Subjects between the ages of 40 and 49 years were randomly invited to attend their local primary care centre. H. pylori status was evaluated by (13)C-urea breath test and infected individuals were randomized to receive omeprazole, 20 mg b.d., clarithromycin, 250 mg b.d., and tinidazole, 500 mg b.d., for 7 days or identical placebos. Economic data on health service costs for dyspepsia were obtained from a primary care note review for the 2 years following randomization. These data were incorporated into a Markov model comparing population H. pylori screening and treatment with no intervention. RESULTS: A total of 2329 of 8407 subjects were H. pylori positive: 1161 were randomized to receive eradication therapy and 1163 to receive placebo. The cost difference favoured the intervention group 2 years after randomization, but this did not reach statistical significance (11.42 ponds sterling per subject cost saving; 95% confidence interval, 30.04 ponds sterling to -7.19 pounds sterling; P=0.23). Analysis by gender suggested a statistically significant dyspepsia cost saving in men (27.17 ponds sterling per subject; 95% confidence interval, 50.01 pounds sterling to 4.32 pounds sterling; P=0.02), with no benefit in women (-4.46 per subject; 95% confidence interval, -33.85 pounds sterling to 24.93 pounds sterling). Modelling of these data suggested that population H. pylori screening and treatment for 1,000,000 45-year-olds would save over 6,000,000 pounds sterling and 1300 years of life. The programme would cost 14, 200 pounds sterling per life year saved if the health service dyspepsia cost savings were the lower limit of the 95% confidence intervals and H. pylori eradication had only a 10% efficacy in reducing mortality from distal gastric cancer and peptic ulcer disease. CONCLUSIONS: Modelling suggests that population H. pylori screening and treatment are likely to be cost-effective and could be the first cost-neutral screening programme. This provides a further mandate for clinical trials to evaluate the efficacy of population H. pylori screening and treatment in preventing mortality from gastric cancer and peptic ulcer disease.