Double-blind, Multicenter, Placebo-Controlled Evaluation Of Clarithromycin And Omeprazole For Helicobacter Pylori-Associated Duodenal Ulcer

Background. Eradication of Helicobacter pylori leads to faster ulcer healing and a significant decrease in ulcer recurrence. Clarithromycin is the most effective monotherapy for eradicating H. pylori from the gastric mucosa, and omeprazole frequently is used for the treatment of duodenal ulcer disease, prompting the interest to investigate rigorously the combination of clarithromycin and omeprazole for eradicating H. pylori. Materials and Methods. The aim of this double-blind, randomized, multicenter (n=30), multinational (n=10) study was to compare clarithromycin and omeprazole with omeprazole monotherapy for the eradication of H. pylori from the gastric mucosa, endoscopic healing, and reduction of symptoms and ulcer recurrence in patients with active duodenal ulcer. Patients with active duodenal ulcer associated with H. pylori infection were randomized to receive omeprazole, 40 mg every morning for 14 days, with either clarithromycin, 500 mg, or placebo three times daily, which was followed by omeprazole, 20 mg every morning for 14 days. Patients underwent endoscopy before enrolling in the study, immediately after finishing treatment, and at 4- to 6-week and 6-month follow-up evaluations or at the recurrence of symptoms. Results. Two hundred and eight patients with active duodenal ulcer associated with confirmed H. pylori infection were randomized to treatment with either clarithromycin and omeprazole (n=102) or omeprazole and placebo (n=106). Four to six weeks after treatment was completed, H. pylori was eradicated in 74% (95% confidence interval, 63.0%–82.4%) of patients receiving clarithromycin and omeprazole, compared with 1% (0.0%–6.2%) of patients receiving omeprazole monotherapy (p < .001). Clarithromycin resistance developed in eight patients treated with clarithromycin and omeprazole and in none given omeprazole and placebo. Ulcers, which were healed following treatment in more than 95% of study patients, recurred by the 6-month follow-up visit in 10% (5%–19%) of dual therapy recipients, compared with 50% (39%–61%) of those who took omeprazole alone (p <.001). Conclusion. Clarithromycin and omeprazole dual therapy is simple and well-tolerated and leads to consistently high eradication rates for patients with duodenal ulcer associated with H. pylori infection.     

Long-term follow-up after eradication of Helicobacter pylori with omeprazole, clarithromycin, and tinidazole (OCT regimen) in a Japanese population

BACKGROUND: The long-term benefit of Helicobacter pylori eradication treatment that includes metronidazole on peptic ulcer disease in Japan is unclear. We investigated the rate of H. pylori re-infection and ulcer relapse after H. pylori eradication. MATERIALS AND METHODS: A total of 266 patients with endoscopically confirmed peptic ulcer disease and H. pylori infection were treated with triple therapy of omeprazole 40 mg (20 mg b.i.d.), clarithromycin 800 mg (400 mg b.i.d.), and tinidazole 1000 mg (500 mg b.i.d.) for 7 days. Endoscopy with gastric biopsy was performed before and 1 month, 6 months, 1.5 years, and 3.5 years after therapy. H. pylori status was determined by H. pylori culture, rapid urease test, and histopathology. 13C-urea breath test was done at 6 months after eradication therapy. Treatment was deemed successful when all tests were negative at 6 months after therapy by endoscopic biopsy. RESULTS: Successful H. pylori eradication was achieved in 262/266 (98.5%) patients with peptic ulcer. Total relapse of peptic ulcer occurred in 8/262 (3%) patients after eradication, with 3/262 (1.1%) occurring within 1.5 years after treatment and 5/262 (1.9%) within 3.5 years. All relapsed patients were found to be H. pylori-positive at the time of relapse. Of the 262 patients who experienced eradication, 20 (7.6%) were subsequently re-infected, six (2.3%) within 1.5 years and 14 (5.3%) within 3.5 years. CONCLUSION: Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) is useful for H. pylori eradication in Japan, but there is an appreciable re-infection rate in this population.     

Comparative Treatment of Helicobacter pylori–Positive Duodenal Ulcer Using Pantoprazole at Low and High Doses Versus Omeprazole in Triple Therapy

Background. Helicobacter pylori eradication has become the standard treatment for peptic ulcer disease. H. pylori –eradicating triple therapy with omeprazole plus two antibiotics has been used until recently; however, the efficacy of pantoprazole and antibiotics for H. pylori eradication has not been researched thoroughly until now. The aim of this randomized clinical trial was to verify the efficacy of triple oral therapy comparing the effects of pantoprazole using two different doses versus omeprazole twice daily in H. pylori eradication, in ulcer healing and relapses, and in gastritis improvement.
Materials and Methods. We enrolled 243 patients with H. pylori– positive duodenal ulcer and randomized them into three treatment groups: 84 patients (group Ome40) were assigned to receive omeprazole, 20 mg twice daily, plus amoxicillin, 1 gm twice daily, and clarithromycin, 500 mg twice daily for 10 days; 79 patients (group Pan40) were treated with pantoprazole, 40 mg daily, plus amoxicillin and clarithromycin at the same doses as those of group Ome40; and 80 patients (group Pan80) were treated with pantoprazole, 40 mg twice daily, plus amoxicillin and clarithromycin at the same doses as those of group Ome40.
Results. Ulcer healing was observed in 81 of 84 patients (96.4%) in group Ome40; in 66 of 79 patients (83.5%) in group Pan40; and in 77 of 80 patients (96.2%) in group Pan80. H. pylori was eradicated in 79 of 84 patients (94%) in group Ome40; in 63 of 79 patients (79.7%) in group Pan40; and in 75 of 80 patients (93.7%) in group Pan80.
Conclusions. We found that 10-day triple therapy with amoxicillin, clarithromycin, and either pantoprazole, 80 mg daily, or omeprazole, 40 mg daily, is highly effective in ulcer healing and is very well tolerated, achieving the 90% cure recommended for an ideal first-line anti– H. pylori positive duodenal ulcer treatment regimen.     

Normalization of phospholipids concentration of the gastric mucosa was observed in patients with peptic ulcer after eradication of Helicobacter pylori

Background. Phospholipids concentration in the gastric mucosa decreased in patients with Helicobacter pylori infection. The aim of this study is to examine the effects of eradication of H. pylori on decreasing the phospholipids concentration in the gastric mucosa in patients with gastric or duodenal ulcer. Materials and Methods. Phospholipids (phosphatidylcholine, phosphatidylethanolamine, and sphingonomyeline) were measured in biopsy specimens from the antrum and corpus using thin‐layer chromatography. In H. pylori positive patients with gastric ulcer (n = 26) and duodenal ulcer (n = 13), and H. pylori negative controls (n = 20), the biopsy specimens were obtained before and 3 months after eradication. Eradication was performed using lansoprazole, amoxycillin, and clarithromycin. Results. Compared with the H. pylori negative control group, the concentrations of phosphatidylcholine and phosphatidylethanolamine decreased significantly in the gastric ulcer group in both antrum and corpus mucosa, and in the duodenal ulcer group in antrum mucosa. This decrease returned to the control level after eradication. Conclusions. This study demonstrates that the eradication of H. pylori in patients with peptic ulcer normalized the decrease of phosphatidylcholine and phosphatidylethanolamine in the gastric mucosa.     

Helicobacter pylori. One bacterium and a broad spectrum of human disease! An overview.

Since the historical rediscovery of gastric spiral Helicobacter pylori in the gastric mucosa of patients with chronic gastritis by Warren and Marshall in 1983, peptic ulcer disease has been largely viewed as being of infectious aetiology. Indeed, there is a strong association between the presence of H. pylori and chronic active gastritis in histology. The bacterium can be isolated in not less than 70% of gastric and in over 90% of duodenal ulcer patients. Eradication of the organism has been associated with histologic improvement of gastritis, lower relapse rate and less risk of bleeding from duodenal ulcer. The bacterium possesses several virulence factors enabling it to survive the strong acid milieu inside the stomach and possibly damaging host tissues. The sequence of events by which the bacterium might cause gastric or duodenal ulcer is still not fully elucidated and Koch's postulates have never been fulfilled. In the majority of individuals, H. pylori infection is largely or entirely asymptomatic and there is no convincing data to suggest an increase in the prevalence of peptic ulcer disease among these subjects. An increasingly growing body of literature suggests an association between colonization by H. pylori in the stomach and a risk for developing gastric mucosa-associated lymphoid tissue (MALT), MALT lymphoma, gastric adenocarcinoma and even pancreatic adenocarcinoma. The bacterium has been implicated also in a number of extra-gastrointestinal disorders such as ischaemic heart disease, ischaemic cerebrovascular disease, atherosclerosis, and skin diseases such as rosacea, but a causal role for the bacterium is missing. Eradication of H. pylori thus seems to be a beneficial impact on human health. Various drug regimens are in use to eradicate H. pylori involving the administration of three or four drugs including bismuth compounds, metronidazole, clarithromycin, tetracyclines, amoxycillin, ranitidine, omeprazole for 1-2 weeks. The financial burden, side effects and emergence of drug resistant strains due to an increase in the use in antibiotics for H. pylori eradication therapy need further reconsideration.     

Current Management Strategies in Acid-Related Disorders

Acid-related disorders include not only reflux esophagitis and peptic ulcer, but also a subset of patients with endoscopy-negative dyspepsia. The management strategy differs between these diseases and therefore a precise diagnosis is important. The unaided clinical diagnosis is of limited value in patients with pain or discomfort in the upper abdomen, and endoscopy is therefore an important and cost-effective diagnostic tool.Duodenal ulcer is caused by an interplay between gastric acid and Helicobacter pylori. The treatment is aimed at rapid symptom relief and healing and at the same time eradication of H. pylori. At present the best choice is the combination of a proton pump inhibitor and two effective antimicrobial drugs, e.g., clarithromycin and metronidazole. The proton pump inhibitor has dual effect in this combination it provides optimal symptom relief and healing, and it increases the anti-H. pylori-effect of the antimicrobial drugs. The risk of reinfection varies geographically; in Europe it is around 1 percent per year, and cure of the infection provides long-term, maybe life-long, cure of the ulcer disease. Some gastric ulcers are not H. pylori-related and the treatment strategy therefore includes a diagnostic test for this infection. If positive, treatment is similar to that in duodenal ulcer, while H. pylori-negative gastric ulcer patients are treated with antisecretory drugs alone.Reflux esophagitis correlates with the degree of acid exposure to the esophagus, and intensive acid inhibition is the most effective non-surgical therapy. In most cases the disease is chronic and needs continuous long-term therapy to prevent relapse. A staged reduction in dosage of the acid inhibitory drug may be attempted when the esophagitis is healed and the patient has become symptom free, but full dose therapy is often needed.Patients with endoscopy-negative dyspepsia are a heterogenous group and a more precise identification of the cause of the symptoms is a prerequisite for rational treatment. Empiric treatment can be tried in patients without alarm symptoms like bleeding or a palpable abdominal mass, and often an acid inhibitory drug is used. A more precise identification of those patients who have acid-related symptoms is possible using placebo controlled single-subject trials with an effective acid inhibitory drug, but in daily routine these drugs are simply given for a short period of time, and in case symptomatic relief is observed, the symptoms may be regarded as being acid-related and treated accordingly.     

The HOMER Study: the effect of increasing the dose of metronidazole when given with omeprazole and amoxicillin to cure Helicobacter pylori infection

Background. Helicobacter pylori eradication with omeprazole, amoxycillin, and metronidazole is both effective and inexpensive. However, eradication rates with different dosages and dosing vary, and data on the impact of resistance are sparse. In this study, three different dosages of omeprazole, amoxycillin, and metronidazole were compared, and the influence of metronidazole resistance on eradication was assessed. Methods. Patients (n = 394) with a positive H. pylori screening test result and endoscopy‐proven duodenal ulcer in the past were enrolled into a multicenter study performed in four European countries and Canada. After baseline endoscopy, patients were randomly assigned to treatment for 1 week with either omeprazole, 20 mg twice daily, plus amoxycillin, 1,000 mg twice daily, plus metronidazole, 400 mg twice daily (low M); or omeprazole, 40 mg once daily, plus amoxycillin, 500 mg three times daily, plus metronidazole, 400 mg three times daily (medium M); or omeprazole, 20 mg twice daily, plus amoxycillin, 1,000 mg twice daily, plus metronidazole, 800 mg twice daily (high M). H. pylori status at entry was assessed by a ¹³C urea breath test and a culture. Eradication was defined as two negative ¹³C‐urea breath test results 4 and 8 weeks after therapy. Susceptibility testing using the agar dilution method was performed at entry and in patients with persistent infection after therapy. Results. The eradication rates, in terms of intention to treat (ITT) (population n = 379) (and 95% confidence interval [CI]) were as follows: low M 76% (68%, 84%), medium M 76% (68%, 84%), and high M 83% (75%, 89%). By per‐protocol analysis (population n = 348), the corresponding eradication rates were: low M 81%, medium M 80%, and high M 85%. No H. pylori strains were found to be resistant to amoxycillin. Prestudy resistance of H. pylori strains to metronidazole was found in 72 of 348 (21%) of the cultures at entry (range, 10%–39% in the five countries). The overall eradication rate in prestudy metronidazole‐susceptible strains was 232 of 266 (87%) and, for resistant strains, it was 41 of 70 (57%; p < .001). Within each group, the results were as follows (susceptible/resistant): low M, 85%/54%; medium M, 86%/50%; and high M, 90%/75%. There were no statistically significant differences among the treatment groups. 23 strains susceptible to metronidazole before treatment were recultured after therapy failed; 20 of these had now developed resistance. Conclusions. H. pylori eradication rates were similar (approximately 80%) with all three regimens. Metronidazole resistance reduced efficacy; increasing the dose of metronidazole appeared not to overcome the problem or significantly improve the outcome. Treatment failure was generally associated with either prestudy or acquired metronidazole resistance. These findings are of importance when attempting H. pylori eradication in communities with high levels of metronidazole resistance.     

Helicobacter pylori: new developments and treatments

The authors highlight new developments in research on Helicobacter pylori. There is now consensus that all patients with newly diagnosed or recurrent duodenal or gastric ulcers who have a positive test result for H. pylori should be treated for the infection. Patients presenting with complications of ulcers, such as bleeding, should also be treated. H. pylori has recently been classified as a definite human carcinogen by the International Agency for Research on Cancer. In treatment, new combination regimens, consisting of 3 or 4 different drugs, cure the infection in more than 80% of patients. Currently, the best combinations are: (1) omeprazole (or another proton-pump inhibitor), clarithromycin and metronidazole, (2) omeprazole (or another proton-pump inhibitor), clarithromycin and amoxicillin, (3) bismuth subsalicylate, tetracycline and metronidazole, and (4) omeprazole, bismuth subsalicylate, tetracycline and metronidazole.     

Randomised double blind controlled study of recurrence of gastric ulcer after treatment for eradication of Helicobacter pylori infection.

OBJECTIVE: To determine whether eradication of Helicobacter pylori infection reduces recurrence of benign gastric ulceration. DESIGN: Randomised, double blind, controlled study. Patients were randomised in a 1:2 ratio to either omeprazole 40 mg once daily for eight weeks or the same treatment plus amoxycillin 750 mg twice daily for weeks 7 and 8. A 12 month untreated follow up ensued. SETTING: Teaching and district general hospitals between 1991 and 1994. SUBJECTS: 107 patients with benign gastric ulcer associated with H pylori. MAIN OUTCOME MEASURES: Endoscopically confirmed relapse with gastric ulcer (analysed with life table methods), H pylori eradication, and healing of gastric ulcers (Mantel-Haenszel test). RESULTS: 172 patients were enrolled. Malignancy was diagnosed in 19; 24 were not infected with H pylori; four withdrew because of adverse events; and 18 failed to attend for start of treatment, leaving 107 patients eligible for analysis (35 omeprazole alone; 72 omeprazole plus amoxycillin). In the omeprazole/amoxycillin group 93% (67/72; 95% confidence interval 84% to 98%) of gastric ulcers healed and 83% (29/35; 66% to 94%) in the omeprazole group (P = 0.103). Eradication of H pylori was 58% (42/72; 46% to 70%) and 6% (2/35; 1% to 19%) (P < 0.001) and relapse after treatment was 22% (16/72) and 49% (17/35) (life table analysis, P < 0.001), in the two groups, respectively. The recurrence rates were 7% (3/44) after successful H pylori eradication and 48% (30/63) in those who continued to be infected (P < 0.001). CONCLUSIONS: Eradication of H pylori reduces relapse with gastric ulcer over one year. Eradication rates achieved with this regimen, however, are too low for it to be recommended for routine use.     

Fromilide (clarithromycin) in eradication of Helicobacter pylori in patients with duodenal ulcer]

The results of two treatment regimes of duodenal ulcer associated with Helicobacter pylori are presented. The patients of the group I were treated with omeprazole, fromilid (clarithromycin) and metronidazole, the patients of the group II were treated with omeprazole, fromilid (clarithromycin) and furazolidone for 7 days. Then patients of both groups were treated with omeprazole for two weeks. Duodenal ulcer healing was registered for all 10 patients in the group I and for 8 patients (of 10 patients) in the group II. Eradication of H. pylori according to rapid urease test and PCR was confirmed for 9 and 4 patients in the group I and for all 10 patients in the group II.     

Recurrent peptic ulcers in patients following successful Helicobacter pylori eradication: a multicenter study of 4940 patients

Objective. Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection. Methods. This was a multicenter study involving 4940 peptic ulcer patients who were H. pylori negative after successful eradication treatment and were followed for up to 48 months. The annual incidence of ulcer relapse in H. pylori‐cured patients, background of patients with relapsed ulcers, time to relapse, ulcer size, and site of relapsed ulcers were investigated. Results. Crude peptic ulcer recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric, duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively. Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5% and 1.3%, respectively. The recurrence rate was significantly higher in gastric ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs were significantly higher in those with gastric ulcer recurrence compared to duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at the same or adjacent sites as the previous ulcers). Conclusions. Curative treatment of H. pylori infection is useful in preventing ulcer recurrence. Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer tended to recur at the site of the original ulcers.     

Interaction of Helicobacter pylori Infection and Nonsteroidal Anti‐Inflammatory Drugs in Gastric and Duodenal Ulcers

Background: Gastric (GU) and duodenal ulcers (DU) are in most instances either induced by Helicobacter pylori infection or by nonsteroidal anti‐inflammatory drugs (NSAIDs). Whether eradication of H. pylori is beneficial in NSAID users for preventing NSAID induced GU and DU has been the focus of different studies. Materials and Methods: Mechanisms shared by both H. pylori and NSAIDs for the induction of GU and DU were reviewed and randomized controlled trials on H. pylori eradication for prevention and healing of GU and DU in patients requiring NSAID therapy were identified by a PubMed search. Results: Key factors in the induction of GU and DU for both H. pylori and NSAIDs are a decrease in pH, imbalance between apoptosis and proliferation, reduction in mucosal blood flow, and recruitment of polymorphonucleates in distinct compartments. For primary ulcer prevention, H. pylori eradication before starting an NSAID therapy reduces the risk of NSAID induced GU and virtually abolishes the risk of DU. H. pylori eradication alone is not sufficient for secondary prevention of NSAID induced GU and DU. H. pylori infection appears to further increase the protective effects of proton‐pump inhibitors (PPI) to reduce the risk of ulcer relapse. H. pylori eradication does not influence the healing of both GU and DU if NSAID intake is discontinued. Conclusions: Duodenal ulcer is more closely related to H. pylori infection than GU in NSAID users. H. pylori eradication is recommended for primary prevention of GU and DU in patients requiring NSAID therapy. PPI therapy is mandatory for secondary prevention of gastroduodenal ulcers, and appears to further reduce the risk of ulcer relapse in the presence of H. pylori.     

A Randomized Clinical Trial to Determine the Efficacy of Regimens Containing Clarithromycin, Metronidazole, and Amoxicillin Among Histologic Subgroups for Helicobacter pylori Eradication in a Developing Country

Background: Most treatments deemed effective for Helicobacter pylori eradication in developed countries are less effective in developing countries. Regimens containing clarithromycin, metronidazole, and amoxicillin seem efficacious despite antibiotic resistance, and may be a viable option in developing countries. Materials and Methods: We evaluated the efficacy of a 14‐day regimen with 500 mg clarithromycin b.i.d., 500 mg metronidazole t.i.d., and 500 mg amoxicillin t.i.d. (with and without a proton pump inhibitor), and a 10‐day regimen containing 500 mg clarithromycin b.i.d., 1 g amoxicillin b.i.d., and 20 mg omeprazole b.i.d. in Pasto, Colombia, using a randomized, single‐blind design stratified by presence of atrophic gastritis. Results: H. pylori was eradicated in 86.8% and 85.3% of the participants randomized to a clarithromycin‐metronidazole‐amoxicillin and clarithromycin‐amoxicillin‐omeprazole regimens, respectively (p = .79). Per‐protocol analyses indicated greater efficacy for the clarithromycin‐metronidazole‐amoxicillin regimen (97%) versus the clarithromycin‐amoxicillin‐omeprazole regimen (86%) (p = .04), particularly for participants with atrophic gastritis (clarithromycin‐metronidazole‐amoxicillin = 100%, clarithromycin‐amoxicillin‐omeprazole = 81%; p = .02). Adverse events were mild, but adverse event‐related non‐compliance was reported more often for regimens containing clarithromycin, metronidazole, and amoxicillin. Conclusions: Our results suggest that an eradication rate of > 85% can be achieved with 14‐day clarithromycin, metronidazole, and amoxicillin and 10‐day clarithromycin, amoxicillin, and omeprazole regimens in Pasto, Colombia. The regimens containing clarithromycin, metronidazole, and amoxicillin appear to be superior to the clarithromycin, amoxicillin, and omeprazole regimen for compliant participants and those with atrophic gastritis. Our findings provide treatment options for a population in a developing country with a high prevalence of H. pylori infections and antibiotic resistance.     

'Rescue' therapy with rifabutin after multiple Helicobacter pylori treatment failures

Aim. Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin is extensively used, although it fails in a considerable number of cases. A ‘rescue’ therapy with a quadruple combination of omeprazole, bismuth, tetracycline and metronidazole (or ranitidine bismuth citrate with these same antibiotics) has been recommended, but it still fails in approximately 20% of cases. Our aim was to evaluate the efficacy and tolerability of a rifabutin‐based regimen in patients with two consecutive H. pylori eradication failures. Patients and Methods. Design: Prospective multicenter study. Patients: Consecutive patients in whom a first eradication trial with omeprazole, clarithromycin and amoxicillin and a second trial with omeprazole, bismuth, tetracycline and metronidazole (three patients) or ranitidine bismuth citrate with these same antibiotics (11 patients) had failed were included. Intervention: A third eradication regimen with rifabutin (150 mg bid), amoxicillin (1 g bid) and omeprazole (20 mg bid) was prescribed for 14 days. All drugs were administered together after breakfast and dinner. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. Outcome: H. pylori eradication was defined as a negative ¹³C‐urea breath test 8 weeks after completing therapy. Results. Fourteen patients have been included. Mean age ± SD was 42 ± 11 years, 41% males, peptic ulcer (57%), functional dyspepsia (43%). All patients took all the medications and completed the study protocol. Per‐protocol and intention‐to‐treat eradication was achieved in 11/14 patients (79%; 95% confidence interval = 49–95%). Adverse effects were reported in five patients (36%), and included: abdominal pain (three patients), nausea and vomiting (one patient), and oral candidiasis (one patient); no patient abandoned the treatment due to adverse effects. Conclusion. Rifabutin‐based rescue therapy constitutes an encouraging strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole and tetracycline.     

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 anti-microbials: 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.     

Twice-Daily Versus Thrice-Daily Clarithromycin in Combination with Ranitidine Bismuth Citrate in the Eradication of Helicobacter pylori

Background. Ranitidine bismuth citrate (RBC), 400 mg bid for 4 weeks, plus clarithromycin, 500 mg tid, is a regimen approved by the US Food and Drug Administration for the eradication of Helicobacter pylori in patients with duodenal ulcers. Proof that the clarithromycin portion of the regimen could be given twice daily without loss of efficacy would reduce cost and improve patient compliance. The objective of this study was to compare the H. pylori eradication rates in patients who had duodenal ulcer and were randomly assigned to 4 weeks of treatment with RBC, 400 mg bid, in conjunction with 2 weeks of therapy with either clarithromycin, 500 mg tid, or clarithromycin, 500 mg bid. Patients and Methods. Patients who had a duodenal ulcer and were H. pylori–positive by at least two tests were randomly assigned to (1) RBC, 400 mg bid for 4 weeks, plus clarithromycin, 500 mg tid for 2 weeks, or (2) RBC, 400 mg bid for 4 weeks, plus clarithromycin, 500 mg bid for 2 weeks. H. pylori eradication was assessed 4 weeks after completion of RBC plus clarithromycin. Results. Three hundred eighty-three patients from 78 centers had a duodenal ulcer and were H. pylori–positive. The modified intent-to-treat (MITT) and the per-protocol (PP) eradication rates were statistically equivalent between the twice-daily (65% MITT, 74% PP) and thrice-daily (63% MITT, 73% PP) clarithromycin treatment regimens. Incidence and types of adverse events did not differ between the two groups. Conclusions. For eradicating H. pylori in patients with duodenal ulcer, clarithromycin, 500 mg bid for 2 weeks, with RBC, 400 mg bid for 4 weeks, is equivalent to clarithromycin, 500 mg tid with RBC. The potential enhancement of patient compliance, reduced cost of clarithromycin, and equivalent efficacy would support the use of twice-daily clarithromycin in triple-therapy regimens with RBC.     

Indications for treatment of Helicobacter pylori infection: a systematic overview.

OBJECTIVE: To determine (a) the advantages and disadvantages of treatment options for the eradication of Helicobacter pylori and (b) whether eradication of H. pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and gastric cancer. DATA SOURCES: A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric cancer, dyspepsia and clinical trial. Six journals and Current Contents were searched manually for pertinent articles published in that time frame. STUDY SELECTION: For duodenal ulcer the search was limited to studies involving adults, studies of H. pylori eradication and randomized clinical trials comparing anti-H. pylori therapy with conventional ulcer treatment. For nonulcer dyspepsia with H. pylori infection the search was limited to placebo-controlled randomized clinical trials. DATA EXTRACTION: The quality of each study was rated independently on a four-point scale by each author. For the studies of duodenal ulcer the outcome measures assessed were acute ulcer healing and time required for healing, H. pylori eradication and ulcer relapse. For the studies of nonulcer dyspepsia with H. pylori infection the authors assessed H. pylori eradication, the symptoms used as outcome measures and whether validated outcome measures had been used. DATA SYNTHESIS: Eight trials involving duodenal ulcer met our inclusion criteria: five were considered high quality, two were of reasonable quality, and one was weak. Six trials involving nonulcer dyspepsia met the criteria, but all were rated as weak. Among treatment options triple therapy with a bismuth compound, metronidazole and either amoxicillin or tetracycline achieved the highest eradication rates (73% to 94%). Results concerning treatment indications for duodenal ulcer were consistent among all of the studies: when anti-H. pylori therapy was added to conventional ulcer treatment acute ulcers healed more rapidly. Ulcer relapse rates were dramatically reduced after H. pylori eradication. All of the studies involving nonulcer dyspepsia assessed clearance rather than eradication of H. pylori. No study used validated outcome measures. A consistent decrease in symptom severity was no more prevalent in patients in whom the organism had been cleared than in those taking a placebo. Of the studies concerning gastric cancer none investigated the effect of eradication of H. pylori on subsequent risk of gastric cancer. CONCLUSIONS: There is sufficient evidence to support the use of anti-H. pylori therapy in patients with duodenal ulcers who have H. pylori infection, triple therapy achieving the best results. There is no current evidence to support such therapy for nonulcer dyspepsia in patients with H. pylori infection. Much more attention must be paid to the design of nonulcer dyspepsia studies. Also, studies are needed to determine whether H. pylori eradication in patients with gastritis will prevent gastric cancer.     

The effects of nocturnal acid breakthrough on Helicobacter pylori eradication

Background. The effects of nocturnal gastric acid breakthrough (NAB) on Helicobacter pylori eradication are still unknown in peptic ulcer patients. The purposes of this study were to compare the effect of lansoprazole 30 mg twice a day (bid) to lansoprazole 60 mg once a day (qd) on the prevalence of NAB, and to determine whether NAB affects the eradication of H. pylori in peptic ulcer patients. Methods. Experiments were carried out in 67 patients with H. pylori‐positive peptic ulcers. They were randomized into two groups, one treated with a combination of lansoprazole 60 mg, clarithromycin 1.0 g, and amoxycillin 2.0 g once a day before breakfast (qd group), and the other, divided doses of the drugs were given before breakfast and dinner (bid group) for 2 weeks. Results. NAB occurred in 31 patients, 55.2% in qd group, and 39.5% in bid group (p = .226). H. pylori eradication was achieved in 61.3% in NAB positive group and 83.3% in NAB negative group (p = .055). The mean duration of NAB for H. pylori eradication group was 99.3 ± 22.7 min, and 293.2 ± 49.8 min for H. pylori persistence group (p < .05). The median intragastric pH of the H. pylori eradication and persistence group was 5.7 ± 0.2 and 4.2 ± 0.4, respectively (p < .05). Conclusions. Neither the morning dose and the divided dose regimen of lansoprazole affected the intragastric acidity and occurrence of the NAB. NAB did not influence H. pylori eradication in peptic ulcer patients, but the duration of NAB and total intragastric median pH were found to influence the H. pylori eradication.     

A Randomized Controlled Trial: Efficacy and Safety of Azithromycin,Ofloxacin, Bismuth,and Omeprazole Compared With Amoxicillin,Clarithromycin, Bismuth,and Omeprazole as Second‐Line Therapy in Patients With Helicobacter pylori Infection

Background: Helicobacter pylori infection of the stomach is widespread among human populations and is considered to play a major role in the pathogenesis of various diseases such as peptic ulcer, adenocarcinoma, and mucosa associated lymphoid tissue (MALT) lymphoma of the stomach. To increase H. pylori eradication rate without increasing bacterial resistance, various regimens have been recommended. Commonly the association of at least two antibiotics with a proton‐pump inhibitor is used. The treatment regimens for second‐line therapy, suggested in studies from the western world may not be ideal in Iran. Aim: In this study, we evaluated the safety and efficacy of a new quadruple therapy regimen and compared it with the standard second‐line treatment for H. pylori eradication. Methods: We selected 220 H. pylori positive patients, with a clear indication of eradication therapy, who did not respond to a 2 weeks treatment with metronidazole, amoxicillin, omeprazole, and bismuth. They were randomized into two groups. Group A (n = 110) were treated with azithromycin, ofloxacin, bismuth, and omeprazole and group B (n = 110) with amoxicillin, clarithromycin, bismuth, and omeprazole for 2 weeks. Four weeks after the end of treatment, urea breath test was performed for all subjects to confirm eradication. Results: In intention‐to‐treat analysis, the rate of H. pylori eradication in groups A and B was 77.3% (85/110) and 64.5% (71/110) respectively (p = .027). In per‐protocol analysis, the rate of H. pylori eradication in groups A and B was 86.7 and 74.7%, respectively (p = .026). The incidence of poor compliance was lower, although not significantly so, in group A than group B (3.5 vs 4.3%). No major adverse events occurred in both groups. Conclusion: Two weeks of treatment with ofloxacin, azithromycin, omeprazole, and bismuth is an effective and safe regimen for H. pylori eradication as second‐line therapy.