Do Japanese and Swedish peptic ulcer patients respond differently to Helicobacter pylori eradication therapies and what are their histological features?

BACKGROUND: As a consequence of gastric histological differences, Japanese and Swedish peptic ulcer (PU) patients may respond differently to Helicobacter pylori eradication therapies. METHODS: The study was single-blind and compared four eradication therapies in Japanese and Swedish patients with healed gastric (GU) or duodenal (DU) ulcer. Swedish patients received either (a) omeprazole+clarithromycin (OC, where O = 20 mg, C = 500 mg) for 2 weeks, or triple therapy with (b) omeprazole + amoxicillin + clarithromycin (OAC-L where O = 20mg, A = 1 g, C = 250 mg); (c) OAC-H (where O = 20 mg, A-1 g, C-500 mg); or (d) omeprazole + metronidazole + clarithromycin (OMC, where O = 20 mg, M = 400 mg, C = 250 mg) for 1 week. Antibiotic doses were weight-adjusted downwards in Japanese patients. H. pylori was assessed using the urea breath test (UBT), histology and culture pre-entry, with UBT being repeated 4 and 8 weeks after stopping treatment. Histology and culture were repeated if the UBT was positive post-therapy. RESULTS: Recruitment included 120 patients from Japan (43 GU, 61 DU, 16 GU+DU) and 120 from Sweden (119 DU, 1 GU+DU). There were 26 exclusions from a FAS analysis due to H. pylori negativity (14), no drug administration (7) or no data after visit 1 (5). Eradication rates (FAS) from Japan were (a) 63%, (b) 93%, (c) 96% or (d) 96%, and for Sweden (a) 92%, (b) 86%, (c) 93% or (d) 96%. Dual therapy was less effective in patients with gastric atrophy associated with GU disease. Tolerability was good in all treatment groups, with no serious adverse events. CONCLUSION: Triple therapies were safe and effective for H. pylori eradication in Japanese and Swedish peptic ulcer patients. Dual therapy was significantly less effective in the Japanese patients, half of whom had a history of GU and more abnormal histology than in the Swedish patients, all of whom had DU.

Comparison of gastric histology among Swedish and Japanese patients with peptic ulcer and Helicobacter pylori infection.

BACKGROUND: The natural course of Helicobacter pylori gastritis may vary between different ethnic groups. Gastric histopathology and the occurrence of H. pylori organisms in the stomach were investigated in healed duodenal (DU) and gastric (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial. METHODS: In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological gastritis variables and H. pylori were assessed from biopsy specimens obtained using a specific sampling protocol and interpreted according to guidelines of the updated Sydney grading system. RESULTS: The ratio of GU:DU was observed to be very different between the recruited Japanese (39:55) and Swedish (0:109) patients. A comparison of data from SDU and JDU showed that the prevalence of H. pylori infection and the antral predominant gastritis demonstrated by both SDU and JDU were essentially identical. A comparison of data from JDU and JGU demonstrated a greater prevalence of H. pylori infection in the antrum, but not corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all patients. CONCLUSIONS: The site specified biopsy methodology and standardized interpretation criteria utilized in this study clearly show that the histotopographic profile of Swedish and Japanese DU patients is essentially the same.

Comparison of Gastric Histology Among Swedish and Japanese Patients with Peptic Ulcer and <emph type="2">Helicobacter pylori</emph> Infection.

BACKGROUND: The natural course of Helicobacter pylori gastritis may vary between different ethnic groups. Gastric histopathology and the occurrence of H. pylori organisms in the stomach were investigated in healed duodenal (DU) and gastric (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial. METHODS: In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological gastritis variables and H. pylori were assessed from biopsy specimens obtained using a specific sampling protocol and interpreted according to guidelines of the updated Sydney grading system. RESULTS: The ratio of GU:DU was observed to be very different between the recruited Japanese (39:55) and Swedish (0:109) patients. A comparison of data from SDU and JDU showed that the prevalence of H. pylori infection and the antral predominant gastritis demonstrated by both SDU and JDU were essentially identical. A comparison of data from JDU and JGU demonstrated a greater prevalence of H. pylori infection in the antrum, but not corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all patients. CONCLUSIONS: The site specified biopsy methodology and standardized interpretation criteria utilized in this study clearly show that the histotopographic profile of Swedish and Japanese DU patients is essentially the same.

Effect of budesonide enema on remission and relapse rate in distal ulcerative colitis and proctitis.

BACKGROUND: Glucocorticosteroid enemas are equally effective as 5-ASA enemas in the treatment of active distal ulcerative colitis (UC). With the introduction of budesonide, the risk of systemic side effects may be reduced. We investigated whether budesonide enema, 2 mg/100 ml, administered twice daily (b.i.d.) could increase the remission rate in comparison with the once daily (o.d.) standard regimen. Furthermore, we evaluated whether 2 mg budesonide enema, given twice weekly, could have a relapse preventing effect. METHODS: 149 patients with active distal UC were treated in a controlled, double-blind multicentre study with two parallel groups: placebo enema in the morning and budesonide enema in the evening (i.e. 2 mg/day) or budesonide enema b.i.d. (i.e. 4 mg/day) until remission (absence of clinical symptoms and endoscopic healing) or at most 8 weeks. Patients in remission were randomized to either budesonide enema or placebo enema twice weekly for 24 weeks or until relapse. RESULTS: The remission rates at 4 weeks were 33% for o.d. and 41% for b.i.d. regimens (NS) and correspondingly 51% and 54% at 8 weeks (NS). The b.i.d. group had an increased frequency of impaired adrenal function, 32% versus 4.8% (P = 0.001). The relapse rates during maintenance treatment with budesonide enema and placebo were 15% versus 24% after 8 weeks, 31% versus 27% after 16 weeks and 41% versus 51% after 24 weeks (NS). CONCLUSION: Budesonide enema 2 mg o.d. appears to be the optimal dosage in active distal UC. We could not show that budesonide enema twice weekly is sufficient to maintain remission.

Symposium: Helicobacter pylori and clinical risks--focus on gastro-oesophageal reflux disease.

Helicobacter pylori is a gastric pathogen that is a major cause of peptic ulcer disease, has a role in mucosa-associated lymphoid tissue (MALT) lymphoma and is associated with gastric cancer. Yet, in a large proportion of the human population, H. pylori infection has no apparent adverse clinical consequences. Furthermore, recent research suggests that H. pylori may even confer protection against gastroesophageal reflux disease. The conflicting evidence surrounding H. pylori infection was discussed at a sponsored symposium in Helsinki, introduced by Professor P. Malfertheiner, with papers presented by Dr H. J. O'Connor, Professor R. M. Genta, Dr P. Unge and Professor A. T. R. Axon. Emerging epidemiological and retrospective evidence suggests that the presence of H. pylori infection may provide some protection against gastroesophageal reflux disease, but there is other evidence that shows no benefit of H. pylori for the protection of the oesophagus. It was felt that prospective, multicentre studies are needed to explore the H. pylori-gastroesophageal disease relationship further, to avoid confusing potential benefits with known risks. Following the symposium, a discussion on the relative risks and benefits for H. pylori eradication was provided by Professor Axon and Professor Blaser. Eradication of H. pylori has been recommended in a series of management guidelines issued by consensus groups. However, accurate estimates of the relative risks and benefits of H. pylori infection in the general population, as well as in specific patient groups, is essential in order to develop a management strategy.

Effect of profound acid suppression in functional dyspepsia: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment. METHODS: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d (n = 100) or placebo (n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards. RESULTS: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% Cl of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy. CONCLUSION: A subset of patients with FD will respond to therapy with omeprazole.

Antimicrobial susceptibility testing of Helicobacter pylori in a large multicenter trial: the MACH 2 study.

Culture and susceptibility testing of Helicobacter pylori strains was performed in a large multinational, multicenter randomized clinical trial. Culture was carried out on gastric biopsy samples obtained from 516 patients at entry and had a sensitivity of 99% when the [(13)C]urea breath test was used as a reference. Susceptibility testing was performed for clarithromycin and metronidazole on 485 strains by an agar dilution method and the epsilometer test (Etest) and for amoxicillin by an agar dilution method only. Resistance to clarithromycin (>1 microgram/ml) was found in 3% of the H. pylori strains, with a perfect correlation between Etest and agar dilution methods. Resistance to metronidazole (>8 microliter/ml) was found in 27% of the strains by agar dilution, but there were important discrepancies between it and the Etest method. No resistance to amoxicillin was found. The logarithms of the MICs of the three antibiotics against susceptible strains had a distribution close to normal. The impact of resistance was tested in the four arms of the trial. There were not enough clarithromycin-resistant strains to evaluate the impact of resistance on the cure rate of clarithromycin-based regimens. For metronidazole-resistant strains, the impact noted in the clarithromycin-metronidazole arm was partially overcome when omeprazole was added (76% eradication for resistant strains versus 95% for susceptible strains). Secondary resistance to clarithromycin occurred in strains from 12 of 105 patients (11.4%) after the failure of a clarithromycin-based regimen to effect eradication. The detection of point mutations in clarithromycin-resistant strains was performed by a combination of PCR and restriction fragment length polymorphism. Mutations (A2142G and 2143G) were found in all strains tested except one. This study stresses the importance of performing susceptibility tests in clinical trials in order to explain the results of different treatments.

The OAC and OMC options.

OBJECTIVE: In three studies, the two most successful regimens in the MACH1 study (omeprazole-amoxycillin-clarithromycin (OAC) and omeprazole-metronidazole-clarithromycin (OMC)) were investigated further. DESIGN: Double-blind, randomized, international, multi-centre studies with parallel groups. SETTING: The studies were performed at centres in France, Germany, Ireland, Norway, Sweden and the UK (MACH2), Canada (DU-MACH) and Germany, Hungary and Poland (GU-MACH). PARTICIPANTS AND INTERVENTIONS: In MACH2, the influence of omeprazole on eradication was investigated in patients with duodenal ulcers in remission, using OAC, AC, OMC and MC. In DU-MACH and GU-MACH, eradication and relapse rates were investigated in patients with active peptic ulcers, using: OAC, OMC and omeprazole alone. MAIN OUTCOME MEASURES: Eradication of Helicobacter pylori. In patients with active peptic ulcer, ulcer healing was also assessed. RESULTS: In MACH2 (n = 514, intention-to-treat (ITT) analysis), the addition of omeprazole to AC increased the eradication rate from 26 to 94%. The corresponding increase for MC/ OMC was from 69 to 87%. The efficacy of the AC and OAC regimens was unaffected by primary metronidazole resistance, while that of MC was halved and that of OMC reduced by 15%. Clarithromycin resistance was uncommon. In DU-MACH and GU-MACH (n = 146 and 145, ITT analysis), eradication rates were high with both regimens. Ulcer healing rates were also high in all treatment groups; ulcer relapse was significantly less frequent in the OAC and OMC groups. All regimens were well tolerated. CONCLUSION: Omeprazole triple therapy is highly effective in patients with active or healed peptic ulcer disease, and is well tolerated.

The GU-MACH study: the effect of 1-week omeprazole triple therapy on Helicobacter pylori infection in patients with gastric ulcer.

AIMS: To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer, and to assess healing and relapse of gastric ulcer. METHODS: A double-blind, randomized study was carried out in 18 centres in Germany, Hungary and Poland. Patients (n = 160) with gastric ulcer and a positive H. pylori screening test were randomized to a 7-day twice daily treatment with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1000 mg (OAC) or omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg (OMC), or with omeprazole 20 mg once daily (O). After completion of this 1-week treatment, patients were treated with omeprazole until healing (maximum 12 weeks), and followed for 6 months. H. pylori was assessed by urea breath test (UBT) and histology. RESULTS: Eradication rates ITT were OAC 79% (95% CI: 65-90%), OMC 86% (95% CI: 73-94%) and O 4% (95% CI: 0-14%). Eradication rates PP were OAC 83% (95% CI: 68-93%), OMC 93% (95% CI: 80-98%) and O 3% (95% CI: 0-13%). Gastric ulcer relapses occurred in 5, 0 and 11 patients in the groups, respectively. CONCLUSIONS: The results from the study demonstrate that OMC and OAC 1-week regimens are safe and effective for eradication of H. pylori in gastric ulcer patients, and that ulcer relapse is infrequent after successful eradication.

The DU-MACH study: eradication of Helicobacter pylori and ulcer healing in patients with acute duodenal ulcer using omeprazole based triple therapy.

AIM: To investigate the efficacy of two omeprazole triple therapies for the eradication of Helicobacter pylori, ulcer healing and ulcer relapse during a 6-month treatment-free period in patients with active duodenal ulcer. METHODS: This was a double-blind, randomized study in 15 centres across Canada. Patients (n = 149) were randomized to omeprazole 20 mg once daily (O) or one of two 1-week b. d. eradication regimens: omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (OMC) or omeprazole 20 mg, amoxycillin 1000 mg and clarithromycin 500 mg (OAC). All patients were treated for three additional weeks with omeprazole 20 mg once daily. Ulcer healing was assessed by endoscopy after 4 weeks of study therapy. H. pylori eradication was determined by a 13C-urea breath test and histology, performed at pre-entry, at 4 weeks after the end of all therapy and at 6 months. RESULTS: The intention-to-treat (intention-to-treat) analysis contained 146 patients and the per protocol (per protocol) analysis, 114 patients. The eradication rates were (intention-to-treat/per protocol): OMC-85% and 92%, OAC-78% and 87% and O-0% (O). Ulcer healing (intention-to-treat) was greater than 90% in all groups. The differences in the eradication and relapse rates between O vs. OMC and O vs. OAC were statistically significant (all, P < 0.001). Treatment was well tolerated and compliance was high. CONCLUSION: The OMC and OAC 1-week treatment regimens are safe and effective for eradication, healing and the prevention of relapse in duodenal ulcer patients.

The MACH2 study: role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies.

BACKGROUND & AIMS: The role of omeprazole in triple therapy and the impact of Helicobacter pylori resistance on treatment outcome are not established. This study investigated the role of omeprazole and influence of primary H. pylori resistance on eradication and development of secondary resistance. METHODS: Patients (n = 539) with a history of duodenal ulcer and a positive H. pylori screening test result were randomized into 4 groups. OAC group received 20 mg omeprazole, 1000 mg amoxicillin, and 500 mg clarithromycin; OMC group received 20 mg omeprazole, 400 mg metronidazole, and 250 mg clarithromycin; and AC (amoxicillin, 1000 mg, and clarithromycin, 500 mg) and MC (metronidazole, 400 mg, and clarithromycin, 250 mg) groups received no omeprazole. All doses were administered twice daily for 1 week. H. pylori status was assessed before and after therapy by 13C-urea breath test. Susceptibility testing was performed at entry and in patients with persistent infection after therapy. RESULTS: Eradication (intention to treat [n = 514]/per protocol [n = 449]) was 94%/95% for OAC, 26%/25% for AC (P < 0.001), 87%/91% for OMC, and 69%/72% for MC (P < 0.001). Primary resistance was 27% for metronidazole, 3% for clarithromycin, and 0% for amoxicillin. Eradication in primary metronidazole-susceptible/-resistant strains was 95%/76% for OMC and 86%/43% for MC. Secondary metronidazole and clarithromycin resistance each developed in 12 patients: 8 treated with omeprazole and 16 without omeprazole. CONCLUSIONS: Addition of omeprazole achieves high eradication rates, reduces the impact of primary resistance, and may decrease the risk of secondary resistance compared with regimens containing only two antibiotics.

Are there more clinically important complications of Helicobacter pylori infection than peptic ulcer disease? A review of current literature.

Helicobacter pylori gastritis (i.e. H. pylori infection and complications) is a focus of tremendous research activity today. Besides peptic ulcer disease, a large number of reports suggest that other diseases are associated with H. pylori. The International Agency for Research on Cancer sponsored by the World Health organization classified the bacterium as a group I carcinogen in 1994. Population-based studies of H. pylori and gastric cancer in 1991 showed an increased odds ratio, of 3-6, in infected patients, and a calculation of odds ratios in different age groups showed a markedly increased odds ratio, to about 20, in younger ages. Studies of non-ulcer dyspepsia and the effect of cure of H. pylori show either none, small, or significant symptom relief, suggesting a positive effect in a subgroup of non-ulcer dyspepsia patients. Mucosa-associated lymphoid tissue-lymphoma caused by H. pylori could be eradicated, at least in its mild forms. Barrett's ulcer is a possible H. pylori-associated disease as well as gastroesophageal reflux disease. Normal feedback in the acid regulation system is changed in infected patients, which may facilitate an increased gastroesophageal acidic reflux. Gastropathy and/or peptic ulcer due to use of nonsteroidal antiinflammatory drugs is probably aggravated by the infection. The infectious disease H. pylori gastritis is associated with a large number of complications, some of which are serious. There are no data showing any advantages of the infection. Giving anti-H. pylori therapy to infected patients should be regarded as essential.

Eradication therapy of Helicobacter pylori. A review. Report from a workshop organized by the Swedish and Norwegian Medical Products Agencies, September 1995.

An expert meeting was organized by the Swedish and Norwegian Medical Products Agencies in September 1995 in order to review the current literature and opinions on detection and treatment of Helicobacter pylori. Ten people from these Agencies and 23 experts participated in the workshop and all were involved in the final manuscript, summarizing the background data and the conclusions (Info Läkemedelsverket 1:96). This report is limited to the therapeutic issues. Therapeutic effect on H. pylori is shown for tetracyclines, nitroimidazoles, clarithromycin, and amoxicillin. Acid inhibitory drugs or bismuth salts increase the antibacterial activity. In vitro resistance to metronidazole is reported in cultures of 10%-40% of H. pylori-infected patients in Scandinavia. Primary resistance to clarithromycin and tetracyclines is rare and no resistance to amoxicillin is confirmed. The clinical significance of resistance is unclear when effective triple combinations are used in previously untreated patients, but should be considered in treatment failures. Recommended therapeutic regimens should achieve a more than 90% cure rate. Important factors when choosing therapy are efficacy, side-effects, ecological factors, duration of therapy, and cost-benefit. Four triple regimens are effective and relatively well documented: omeprazole/amoxicillin/metronidazole for 1 week, omeprazole/clarithromycin/metronidazole for 1 week, omeprazole/clarithromycin/amoxicillin for 1 week, or bismuth subnitrate or bismuth citrate/tetracycline/metronidazole for 10 days. Side-effects are less pronounced in the combinations without bismuth. Dual therapy is not recommended. Eradication therapy should be considered for patients with peptic ulcer disease, MALT-lymphoma and Menetriéré's disease. Triple combinations, including two antimicrobials and a potent acid inhibitory drug or bismuth, are recommended.

Antimicrobial treatment of H. pylori infection--a pooled efficacy analysis of eradication therapies.

OBJECTIVE: To evaluate the clinical efficacy of available therapies directed towards Helicobacter pylori eradication. DESIGN: Pooled overall analyses of a limited number of drug combinations regardless of dosage, duration, formulation etc. SUBJECTS: Helicobacter pylori infected patients with or without complications. INTERVENTIONS: Efficacy data from all studies included in the analysis are transformed to or retained as intention to treat data. MAIN OUTCOME: Efficacy is presented as proportion of patients cured from the infection. Confidence intervals are enlarged by 1.5 due to the inferior strength of a pooled analysis. RESULTS: Dual therapies are ineffective. Triple therapies cure 70-90% of the patients. Well documented high efficacy is shown for a proton pump inhibitor plus two antimicrobials. Less studied but effective alternatives are ranitidine-bismuth plus two antimicrobials. CONCLUSION: A proton pump inhibitor plus two antimicrobials is the best validated highly effective type of eradication therapy.

What other regimens are under investigation to treat Helicobacter pylori infection?

The most common infection in the world, Helicobacter pylori infection, is very specific, and present experience in treating infectious diseases is not applicable in general for this infection. Animal models (e.g., mouse and ferret) are thus far inadequate as reliable screening models. Old-fashioned trial-and-error treatment of infected humans is still the screening model and the gold standard in the evaluation of regimens aimed at eradication of H. pylori. A variety of studies on treatment of H. pylori infection have been performed with varying results. This pooled analysis of the following therapeutic combinations: proton pump inhibitor (PPI) plus two antibiotics or antimicrobials, quadruple therapies, and nonantibiotic regimens is an attempt to make a fair comparison of tested therapeutic strategies aimed at eradicating H. pylori. Data from treatment groups including specified drug combinations are pooled, regardless of dose or duration. Search methods are: MEDLINE 1984-1996, Digestive Disease Week 1988-1996, United European Gastroenterology Week 1992-1996, European Helicobacter pylori Study Group 1988-1996, Asia Pacific Congress 1996, H. pylori International Workshop Hong Kong 1996, and miscellaneous. Eradication rates (efficacy) are presented as intention-to-treat data (i.e., worst-case analysis). Separate subanalyses with regard to study quality, dose, and duration are performed for some groups. A general cost-efficacy analysis is performed based on pooled efficacy data. Convenience data are presented as total number of tablets, total number of intake occasions, and duration of therapy. Drugs evaluated in the analysis are bismuthdicitrate, tetracycline, amoxicillin, nitroimidazoles, macrolides, H2-receptor antagonists, PPIs, sucralfate, and sofalcone. The most effective and convenient drug combinations are the PPI-based triple therapies. No significant difference was observed between the three PPIs. The cure rate did not improve after addition of bismuth. Cost-effectiveness is closely associated with efficacy.

Drug interactions with proton pump inhibitors.

Omeprazole, lansoprazole and pantoprazole are all mainly metabolised by the polymorphically expressed cytochrome P450 (CYP) isoform CYP2C19 (S-mephenytoin hydroxylase). All 3 proton pump inhibitors have a very limited potential for drug interactions at the CYP level. Small effects on CYP reported for these compounds are usually of no clinical relevance. No dose related adverse effects have been identified, suggesting that the small proportion of slow metabolisers is at no additional risk for clinically important drug interactions. The absorption of some compounds, e.g. benzylpenicillin (penicillin G), are altered during treatment with proton pump inhibitors as a result of the increased intragastric pH. A synergy has been confirmed between omeprazole and amoxicillin or clarithromycin in the antibacterial effect against Helicobacter pylori.

Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I Study.

BACKGROUND: Eradication of Helicobacter pylori provides potential cure in the majority of patients with peptic ulcer disease, and eradication rates of more than 90% have been reported, using omeprazole in combination with two antimicrobials. The choice of antimicrobials, dose regimen and duration of treatment have varied between studies, however, and an optimal treatment still has to be established. MATERIALS AND METHODS: We conducted an international, randomized, double-blind, placebo-controlled study involving more than 100 patients in each of six treatment groups in 43 hospital gastrointestinal units in Canada, Germany, Ireland, Sweden, and the United Kingdom. Patients (n = 787) with proved duodenal ulcer disease were randomized to treatment twice daily for 1 week with omeprazole, 20 mg (O), plus either placebo (P) or combinations of two of the following antimicrobials: amoxicillin, 1 gm (A), clarithromycin, 250 or 500 mg (C250, C500), or metronidazole, 400 mg (M). Eradication of H. pylori was evaluated by 13C-UBT, performed before and 4 weeks after treatment cessation. RESULTS: The eradication rates for the all-patients-treated analysis were 96%, OAC500; 95%, OMC250; 90%, OMC500; 84%, OAC250; 79%, OAM; and 1%, OP. OAC500 and OMC250 achieved eradication rates with lower 95% confidence interval limits exceeding 90%. All regimens were well-tolerated, 96% of patients complied with their dose regimen, and 2.3% of the patients discontinued treatment owing to adverse events. CONCLUSIONS: Omeprazole triple therapies given twice daily for 1 week produce high eradication rates, are well-tolerated, and are associated with high patient compliance. The two most effective therapies were those combining omeprazole, 20 mg, with either amoxicillin, 1 gm, plus clarithromycin, 500 mg, or metronidazole, 400 mg, plus clarithromycin, 250 mg, all given twice daily.

Prevention of peptic ulcer and dyspeptic symptoms with omeprazole in patients receiving continuous non-steroidal anti-inflammatory drug therapy. A Nordic multicentre study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause gastroduodenal lesions and dyspeptic symptoms. METHODS: Patients with a history of dyspepsia or uncomplicated peptic ulcer disease and with a need for continuous NSAID treatment were randomized to receive either 20 mg omeprazole once daily or placebo. Gastroduodenal ulcers, erosions, and dyspeptic symptoms were evaluated after 1 and 3 months. RESULTS: During a 3-month study period 4.7% (4 of 85) of omeprazole-treated patients developed peptic ulcer, compared with 16.7% (15 of 90) of patients treated with placebo. This prophylactic effect of omeprazole was sustained independently of previous peptic ulcer history or Helicobacter pylori status. Development of dyspeptic symptoms requiring active treatment, either alone or in combination with ulcer(s) or erosions, occurred in 15.3% (15 of 85) of patients treated with omeprazole and 35.6% of those who received placebo. CONCLUSIONS: Omeprazole, 20 mg once daily, provides effective prophylactic therapy in patients at risk of developing NSAID-associated peptic ulcers or dyspeptic symptoms.

Pooled analysis of anti-Helicobacter pylori treatment regimens.

BACKGROUND: The human pathogen Helicobacter pylori and its association with peptic ulcer has dramatically changed the therapeutic approach to patients with this disease. Successful treatment of the infection has consistently been shown to prevent ulcer recurrence. Published data on therapeutic options are sometimes confusing since only few studies have similar design, drug combinations, dosage, dosing, formulation, patient material, and size. A formal meta-analysis is therefore of limited value. METHOD: Data on anti-H. pylori therapies from a large number of publications are pooled into a few groups based on the combination of drugs, regardless of dosage, duration, etc., of the therapy. A mean success rate is calculated for all studies with subanalysis with regard to study design, size, doses and duration. RESULTS: Triple combinations are needed to achieve a success rate of more than 80%. Bismuth/tetracycline based triple therapy gives 82% success rate (range 43-100%) compared to 85% and 87% success rate (range 72-100% and 43-100%) achieved with omeprazole/clarithromycin based triples respectively. CONCLUSION: Omeprazole/clarithromycin based triple regimens are the most effective anti-H. pylori therapeutic strategies, slightly superior to bismuth triple regimens.