The effect of antibiotic therapy on bleeding from duodenal ulcer

OBJECTIVE: We conducted this study to test whether eradication of Helicobacter pylori (H. pylori) infection prevents hemorrhage related to duodenal ulcer. METHODS: Patients with H. pylori infection and endoscopically proven duodenal ulcers without ulcer-related hemorrhage were enrolled into four randomized, double-blind, multicenter studies using the same study protocol. They were treated with clarithromycin plus omeprazole (441 patients), omeprazole alone (447 patients), or ranitidine alone (263 patients). Success of H. pylori eradication was evaluated by the 13C-urea breath test 4-6 wk after the last dose of study drug. Follow-up continued at monthly intervals up to 1 yr after the last dose of study drug. RESULTS: Bleeding due to duodenal ulcer was not observed in any patients who received clarithromycin plus omeprazole, whereas five patients in the omeprazole treatment group and six patients in the ranitidine treatment group experienced an episode of ulcer-related hemorrhage during follow-up. All patients who experienced ulcer-related bleeding were male. When compared by bleeding, there were no significant differences with respect to ethnicity, alcohol consumption, or tobacco use. H. pylori infection was no longer detectable in 68% of patients after treatment with clarithromycin plus omeprazole, compared with 5% after treatment with omeprazole alone or 4% after treatment with ranitidine alone. CONCLUSION: In a population of duodenal ulcer patients without predisposing risk factors for ulcer bleeding, antibiotic eradication or suppression of H. pylori infection prevented the occurrence of ulcer-related hemorrhage for up to 1 yr after therapy.     

Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage--a long-term randomized, controlled study

OBJECTIVE: Eradication of Helicobacter pylori (H. pylori) in patients with uncomplicated duodenal ulcers prevents long-term recurrence of ulcers. We aimed to study whether treatment of H. pylori prevents the long-term recurrence of duodenal ulcer hemorrhage. METHODS: Patients with duodenal ulcer bleeding and confirmed H. pylori infection were recruited. A total of 120 patients were randomly assigned to triple therapy (DeNoltab 120 mg, amoxycillin 500 mg, and metronidazole 300 mg four times daily) or DeNoltab 120 mg four times daily alone. No maintenance therapy was given during the follow-up period. The endpoints were the cumulative rates of symptomatic and bleeding duodenal ulcer recurrences. RESULTS: Of the patients receiving the triple regimen, 85.1% had H. pylori eradicated as compared to 2.0% of patients receiving DeNoltab (p < 0.05). More patients in the DeNoltab group than those in the Triple group had recurrence of ulcer bleeding, but this did not reach statistical significance (12/60 vs 6/60, p = 0.20). Logistic regression analysis on clinical, personal, and endoscopic characteristics identified persistent H. pylori infection as the only independent predictor of recurrence of duodenal ulcer bleeding. CONCLUSIONS: Treatment of H. pylori alone with the present bismuth-based triple therapy in patients with duodenal ulcer hemorrhage did not result in significant reduction in further bleeding episodes, although a trend was seen for the group that was given triple therapy. On the other hand, posttreatment H. pylori status was found to be an independent predictor of bleeding recurrence.     

Helicobacter pylori-negative duodenal ulcers: prevalence, clinical characteristics, and prognosis--results from a randomized trial with 2-year follow-up

OBJECTIVE: The proportion of Helicobacter pylori-negative duodenal ulcer disease appears to be increasing. Data on clinical outcome and prognosis in this subgroup are lacking. METHODS: Two hundred seventy-six duodenal ulcer patients randomized, irrespective of H. pylori status, to either eradication therapy or maintenance omeprazole (double-blind, double-dummy design) for 1 yr were studied. Patients were followed up for a total of 2 yr, with visits performed every 2 months the first year and every 6 months the following year. Endoscopies for assessment of ulcer relapse were done at 6 and 12 months or in the event of symptomatic relapse. H. pylori status was assessed by culture, immunohistochemistry, and urea breath test at entry, at 6, 12, and 24 months or at failure. The primary endpoint was discontinuation, irrespective of reason. Patients were considered H. pylori negative if all three tests were negative. Patients were considered H. pylori-positive if any of the three diagnostic tests were positive. Study staff were blinded to H. pylori results. RESULTS: Thirty-two (12%) patients were H. pylori negative at entry. There were no differences according to H. pylori status for a number of clinical and demographic characteristics. However, H. pylori-negative patients had a shorter history of ulcer symptoms and were more likely to be NSAID users (19% vs 1%, p < 0.001). Only 28% of the H. pylori-negative patients completed the study, as compared with 40% of H. pylori-positive patients (p = 0.0005). The main reasons for the poorer prognosis in H. pylori-negative patients were relapse of ulcer/ulcer not healed (35% vs 26%) and relapse of severe dyspepsia symptoms without ulcer relapse (16% vs 7%). H. pylori-negative patients randomized to eradication therapy left the study early compared with H. pylori-negative patients randomized to long-term omeprazole therapy. Outcome in omeprazole-treated patients did not differ according to H. pylori status (p = 0.3). CONCLUSIONS: Clinical characteristics in H. pylori-negative and positive duodenal ulcer patients differ little. Clinical outcome over 2 yr is significantly poorer in H. pylori-negative patients, especially if treated empirically with eradication therapy. These results suggest that H. pylori infection should be assessed in all duodenal ulcer patients before treatment is decided.     

Omeprazole and regulation of cytokine profile in Helicobacter pylori-infected patients with duodenal ulcer disease

BACKGROUND/AIMS: To estimate the cytokine profile in Helicobacter pylori-positive patients with duodenal ulcers treated with omeprazole. METHODOLOGY: The subjects were 22 patients with endoscopically defined active duodenal ulcers and H. pylori infection treated with omeprazole for 3 months after initial 1-week triple therapy. Peripheral blood CD3+ CD4+ and CD8+ T lymphocytes, percentage of HLA-DR+ peripheral blood lymphocytes, and cytokine levels (GM-CSF, IL-6 and IL-2) were measured in the supernatants from PHA-cultured peripheral blood lymphocytes at baseline conditions and after 3-months' omeprazole treatment. RESULTS: The H. pylori eradication triple regimen cured H. pylori infection in 86.4% of our patients. Peripheral blood CD3+ CD4+ and CD8+ T lymphocytes were not affected by omeprazole treatment (P > 0.05), whereas the percentage of HLA-DR+ peripheral blood lymphocytes increased significantly post-treatment (P < 0.05). All cytokine levels measured in the supernatants showed a significant decrease after treatment (P < 0.001). CONCLUSIONS: The significant decrease in the two pro-inflammatory cytokines (GM-CSF, IL-6) and the major inflammatory cytokine IL-2, implies that the potential cytokine synthesis of the Th1 pattern from peripheral blood lymphocytes is highly suppressed after treatment. This effect on cytokine regulation seems to be a result of the positive H. pylori infection outcome at the immunological level, which leads to "normalization" of cytokine production.     

One week of treatment with esomeprazole-based triple therapy eradicates Helicobacter pylori and heals patients with duodenal ulcer disease.

BACKGROUND: Proton pump inhibitor (PPI) monotherapy is commonly continued for 3 weeks after Helicobacter pylori eradication with PPI-based triple therapy regimens to ensure duodenal ulcer (DU) healing. This randomized, double-blind, multicentre study evaluated whether only 1 week of triple therapy with the new PPI esomeprazole was sufficient to ensure high rates of ulcer healing and H. pylori eradication. METHODS: A total of 446 H. pylori-positive patients with active DU received twice daily treatment with esomeprazole 20 mg (n = 222) or omeprazole 20 mg (n = 224) in combination with amoxicillin 1 g and clarithromycin 500 mg for 1 week (EAC and OAC, respectively). Patients in the OAC group then received 3 weeks' monotherapy with omeprazole 20 mg once daily; those treated with EAC received placebo. Ulcer healing was assessed by endoscopy on completion of therapy and H. pylori status was assessed by (13)C-urea breath testing and histology 4-6 weeks later. RESULTS: Ulcer healing rates (95% CI) for intention-to-treat and per-protocol populations were: EAC + placebo 91% (87-95%) and 94% (90-97%); OAC + omeprazole 92% (88-95%) and 96% (92-98%). Corresponding H. pylori eradication rates were: EAC + placebo 86% (81-90%) and 89% (84-93%); OAC + omeprazole 88% (83-92%) and 90% (85-93%). Both eradication regimens were well tolerated, and patient compliance was high. CONCLUSIONS: A 1-week regimen of esomeprazole-based triple therapy is sufficient for DU healing and H. pylori eradication in patients with DU disease.     

Effect of omeprazole and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the healing of duodenal ulcer: comparison with a historical control.

BACKGROUND/AIMS: To test the hypothesis of equivalence of an omeprazole 7-day triple therapy without subsequent acid suppression and a historical ranitidine 12-day triple therapy (recruiting phase 1989-91) with subsequent acid suppression in their effect on the eradication of Helicobacter pylori (H. pylori) and the healing of duodenal ulcer. METHODOLOGY: Seventy-seven patients with H. pylori-positive duodenal ulcers received a 7-day treatment with amoxicillin 750 mg tid and metronidazole 500 mg tid. Additional omeprazole 20 mg or 40 mg once daily was given to 39 and 38 of the patients, respectively. Endoscopy was performed before treatment and four weeks after cessation of therapy. RESULTS: The cumulative intention-to-treat (ITT) H. pylori-eradication rate was 66% (51/77) as compared to 89% (46/52) for the historical control (p < 0.05). The corresponding ulcer healing rates were 90% (69/77) and 92% (48/52). Primary metronidazole resistance (PMR) had escalated from 10% to 27% within 6 years resulting in eradication rates of 84% for sensitive and 19% for resistant strains (p < 0.001). PMR could be demonstrated in 45% of all female, but only in 17% of the male patients (p < 0.05). In the patients with H. pylori eradication, the ulcers healed in 98% (50/51) as compared to 73% (19/26) in those with persistent infection (p < 0.005). Analysis based on the presence of PMR showed ulcer healing rates of 95% (53/56) for sensitive and 76% (16/21) for resistant strains (p < 0.05). Improvement of pain also showed a significant correlation with successful eradication. H. pylori-eradication, healing and symptom relief were similar in the omeprazole 20 mg and 40 mg groups. CONCLUSIONS: The effect of amoxicillin plus metronidazole plus antisecretory agent on the eradication of H. pylori has decreased markedly during the past 6 years due to the escalation of PMR. Doubling of the omeprazole dose does not affect outcome. Cure of the infection as well as metronidazole susceptibility enhance duodenal ulcer healing and symptom relief. Acid suppression following a successful 1-week anti-HP therapy is not required for duodenal ulcer treatment.     

Clinical evaluation of four one-week triple therapy regimens in eradicating Helicobacter pylori infection

AIM: To evaluate clinical efficacy of four one-week triple therapies in eradicating Helicobacter pylori infection. METHODS: In this clinical trial, 132 patients with duodenal ulcer and chronic gastritis were randomly divided into four groups, and received treatment with OAC (omeprazole 20 mg + amoxicillin 1 000 mg + clarithromycin 250 mg), OFC (omeprazole 20 mg + furazolidone 100 mg + clarithromycin 250 mg), OFA (omeprazole 20 mg + furazolidone 100 mg + amoxicillin 1 000 mg) and OMC (omeprazole 20 mg + metronidazole 200 mg + clarithromycin 250 mg), respectively. Each drug was taken twice daily for one week. The (13)C urea breath test was carried out 4-8 weeks after treatment to determine the success of H pylori eradication. RESULTS: A total of 127 patients completed the treatment. The eradication rate for H pylori infection was 90.3%, 90.9%, 70.9% and 65.6%, respectively in OAC, OFC OMC and OFA groups. CONCLUSION: A high eradication rate can be achieved with one-week OAC or OFC triple therapy. Thus, one-week triple therapies with OAC and OFC are recommended for Chinese patients with duodenal ulcers and chronic gastritis.     

The long-term reinfection rate and the course of duodenal ulcer disease after eradication of Helicobacter pylori in a developing country

OBJECTIVE: The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) eradication on the natural history of duodenal ulcer disease and the reinfection rate after treatment in a developing country. METHODS: A total of 111 H. pylori-infected patients with duodenal ulcer were treated with either omeprazole or famotidine plus two antibiotics for 2 wk. Those failed to respond to treatment were retreated with bismuth-based triple therapy. RESULTS: The radication rate was 76% (95% CI: 67-83%). Eventually, H. pylori was eradicated in 96 of the 111 patients (86%), who were followed-up clinically and endoscopically for a mean of 37.2 months. The cumulative reinfection rate after eradication (Kaplan-Meier) was 8%+/-3% in yr 1, 11%+/-4% in yr 2, and 13%+/-4% in yr 3. Nine of the 12 reinfections occurred during yr 1. Recurrence of duodenal ulcer was detected in five patients (5.2%), all of them during yr 1 of follow-up. Histologically, gastritis scores (according to the Sydney system) improved significantly after eradication. CONCLUSIONS: In a high prevalence setting, H. pylori eradication and early reinfection rates after treatment are similar to rates observed in a low prevalence environment, whereas the late reinfection rate seems to be higher. However, up to 3 yr after treatment, most treated patients are free of H. pylori infection and/or ulcer activity. Even longer follow-up studies are necessary to determine whether specific retreatment policies are necessary to maintain long term eradication in developing countries.     

Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study.

OBJECTIVE: To determine the effect of treating Helicobacter pylori infection on the recurrence of gastric and duodenal ulcer disease. DESIGN: Follow-up of up to 2 years in patients with healed ulcers who had participated in randomized, controlled trials. SETTING: A Veterans Affairs hospital. PARTICIPANTS: A total of 109 patients infected with H. pylori who had a recently healed duodenal (83 patients) or gastric ulcer (26 patients) as confirmed by endoscopy. INTERVENTION: Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet) and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given. MEASUREMENTS: Endoscopy to assess ulcer recurrence was done at 3-month intervals or when a patient developed symptoms, for a maximum of 2 years. RESULTS: The probability of recurrence for patients who received triple therapy plus ranitidine was significantly lower than that for patients who received ranitidine alone: for patients with duodenal ulcer, 12% (95% CI, 1% to 24%) compared with 95% (CI, 84% to 100%); for patients with gastric ulcer, 13% (CI, 4% to 31%) compared with 74% (44% to 100%). Fifty percent of patients who received ranitidine alone for healing of duodenal or gastric ulcer had a relapse within 12 weeks of healing. Ulcer recurrence in the triple therapy group was related to the failure to eradicate H. pylori and to the use of nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Eradication of H. pylori infection markedly changes the natural history of peptic ulcer in patients with duodenal or gastric ulcer. Most peptic ulcers associated with H. pylori infection are curable.     

Amoxicillin plus omeprazole versus triple therapy for eradication of Helicobacter pylori in duodenal ulcer disease: a prospective, randomized, and controlled study.

Treatment with amoxicillin and omeprazole resulted in encouraging Helicobacter pylori eradication rates in pilot studies that included medium term follow up. These results were evaluated in a prospective, randomised and controlled study. Forty patients with active duodenal ulcer disease and H pylori colonisation of the gastric mucosa were randomly assigned to receive either omeprazole (20 mg twice daily) and amoxicillin suspension (500 mg four times daily) for two weeks (group I) or bismuth subsalicylate (600 mg three times daily), metronidazole (400 mg three times daily), tetracycline (500 mg three times daily), and ranitidine (300 mg in the evening) for two weeks (group II). Study medication was followed in both groups by a four week treatment course with 300 mg ranitidine up to the final examination. One patient from each group was lost to follow up. H pylori was eradicated in 78.9% of group I and 84.2% of group II (p = 1.00). All ulcers in patients on omeprazole plus amoxicillin healed but in the triple treatment group four patients had residual peptic lesions after six weeks (ulcer healing rate: 78.9%, p = 0.11). Complete pain relief occurred after a median duration of 1 day in group I and of 6 days in group II (p = 0.03). There were no major complications in either group but minor side effects were more frequently recorded in patients on triple therapy (63.2% v 15.8%, p < 0.01). In conclusion, two weeks of treatment with omeprazole plus amoxicillin is as good as triple therapy plus ranitidine in eradicating H pylori but seems better with regard to safety, pain relief, and ulcer healing. Thus, amoxicillin plus omeprazole should be recommended as the treatment of choice in eradicating H pylori in patients with duodenal ulcer disease.     

Role of anti-secretory treatment in addition to Helicobacter pylori eradication triple therapy in the treatment of peptic ulcer]

BACKGROUND/AIMS: It is not clear whether the anti-secretory therapy should be continued for symptomatic relief and ulcer healing before or after the eradication of H. pylori in patients with peptic ulcer disease. The aim of this study was to evaluate the effectiveness of additional anti-secretory therapy before or after H. pylori eradication in peptic ulcer disease. METHODS: Thirty eight patients with H. pylori-positive active peptic ulcer were included. Patients were randomly allocated into 3 groups; standard 1-week triple therapy followed by omeprazole (20 mg, qd) for 3 weeks (group A), standard 1-week triple therapy only (group B), and omeprazole (20 mg, qd) for 3 weeks followed by 1-week triple therapy (group C). Endoscopy with the rapid urease test and histology for H. pylori was performed 4-8 weeks after the completion of treatment. The symptom was scored by a visual analog scale. RESULTS: Of the 38 patients, 10 were excluded from the per-protocol analysis of this study. The H. pylori eradication rates were 87.5% (group A), 80.0% (group B) and 90.0% (group C) respectively. The peptic ulcer healing rates were 100% in group A, 70.0% in group B, and 90.0% in group C. There was no difference in H. pylori eradication rates and ulcer healing rates among three groups (p>0.05). Symptom score differences between pre-treatment and post-treatment group were not significantly different (p>0.05). CONCLUSIONS: The standard one week triple therapy with or without 3-weeks anti-secretory treatment with omeprazole before or after the therapy does not affect H. pylori eradication rates, peptic ulcer healing rates, and symptom score improvement.     

Impact of Colloidal Bismuth Subcitrate in the Eradication Rates of Helicobacter pylori Infection-Associated Duodenal Ulcer Using a Short Treatment Regimen with Omeprazole and Clarithromycin: A Randomized Study

Recent trials have shown that duodenal ulcers treated by H2-blockers heal faster if Helicobacter pylori is eradicated concurrently. Objectives : To evaluate the efficacy of a short treatment regimen in H. pylori eradication and ulcer healing and to assess the impact of colloidal bismuth suhnitrate (CBS) in H. pylori eradication rate. Methods : Sixty-one patients with H. pylori -associated duodenal ulcer were randomized in two short treatment groups. Group A patients (31) were given omeprazole 20 mg b.i.d. ± 8 days. Clarithromycin <500 mg, b.i.d. ) and CBS (120 mg, q.i.d. ) were added 24 h after starting omeprazole and were given for 7 days. Group B patients (30) were treated as group A patients but without CBS. Endoseopics were performed at entry and 4 wk after the end of treatment. Presence of H. pylori was assessed at each endoscopy by urease test, and biopsy specimens were examined for histological evidence of gastritis and by Gram stain and culture for H. pylori infection. No patient received follow-up treatment. Results: H. pylori eradication rates were achieved in 25/31 (80.6%) group A patients and in 15/30 (50%) in group B patients ( p = 0.012). Duodenal ulcer healing was documented in 30/31 (96.8%) patients in group A and in 25/30 (83%) patients in group B. Conclusions : The addition of CBS to the double therapy with omeprazole and Clarithromycin substantially improves the eradication rate of H. pylori . Short therapy with omeprazole 20 mg/b.i.d. , clarithro-mycin 500 mg/b,i.d. , and CBS 120 mg/q.i.d. is a safe, well tolerated combination that achieves a 80.6% eradication rate of H. pylori and duodenal ulcer healing rates as good as those achieved by omeprazole 20 mg/d when given for 4 wk.     

Omeprazole enhances efficacy of triple therapy in eradicating Helicobacter pylori.

Triple therapy has been recommended as the most effective treatment for Helicobacter pylori eradication. Despite achieving a comparatively high eradication result, however, around 10% of patients still fail to be cured. Omeprazole can enhance efficacy of single and double antibiotic protocols and is particularly effective when combined with clarithromycin and a nitroimidazole. This study examined the effect of combining triple therapy with omeprazole. A prospective, randomised, unblinded, single centre trial was carried out on consecutive patients with symptoms of dyspepsia and H pylori infection confirmed by rapid urease test, microbiological culture, and histological assessment. Patients were given a five times/day, 12 day course of colloidal bismuth subcitrate chewable tablets (108 mg), tetracycline HCl (250 mg), and metronidazole (200 mg) with either 20 mg omeprazole twice daily (triple therapy+omeprazole) or 40 mg famotidine (triple therapy+famotidine) at night. Compliance and side effects were determined using a standard questionnaire form. One hundred and twenty five of 165 triple therapy+omeprazole patients and 124 of 171 triple therapy+famotidine patients returned for rebiopsy four weeks after completion of treatment. Significantly more triple therapy+omeprazole patients achieved eradication 122 of 125 (97.6%) as assessed by negative urease test, culture, and histological assessment, when compared with 110 of 124 (89%) triple therapy+famotidine patients (p = 0.006; chi 2). There were 30 triple therapy+omeprazole (24%) and 26 triple therapy+famotidine (21%) patients with de novo metronidazole resistant H pylori included in the study. Side effects were mild and infrequent and were comparable in both groups, although pain in duodenal ulcer, gastric ulcer, and oesophagitis patients seemed to subside earlier in those taking omeprazole. Compliance (>95% of drugs taken) was achieved by 98% of patients of both groups. A 12 days regimen of triple therapy with omeprazole is more effective in achieving H pylori eradication than is triple therapy plus famotidine. Use of 20 mg omeprazole twice daily rather than 40 mg famotidine with a 12 day, low dose triple therapy enhances eradication to over 97% whether the H pylori is metronidazole sensitive or resistant.     

Assessment of decisions in the treatment of Helicobacter pylori-related duodenal ulcer: a cost-effectiveness study.

AIMS: Many treatment trials for Helicobacter pylori have been reported but few have evaluated treatment in terms of both cost and effectiveness. It is important to find a therapy with a high eradication rate and low cost, especially in China. The aim of the study is to assess the efficiency of therapy for duodenal ulcers, including ulcer healing, H. pylori eradication and ulcer recurrence. METHODS: Ninety-six consecutive patients with duodenal ulcers and H. pylori infection were randomly allocated into two groups: AMT group (amoxycillin + metronidazole + tagamet); OA group (omeprazole + amoxycillin). Side-effects were recorded during the treatment period. Endoscopic examinations were repeated at the 7th or 8th week to assess ulcer healing. Patients were followed up for 6 months and repeat endoscopy was performed. Ulcer healing rate, H. pylori eradication rate and ulcer recurrence rate were compared. All costs were recorded and a cost-effectiveness analysis was conducted. RESULTS: In the AMT and OA groups, the ulcer healing rate was 83.7 and 93.5%, respectively (P = 0.27). The eradication rate of H. pylori was 65.1 and 69.6%, respectively and was significantly higher in patients with an ulcer diameter < or = 1 cm compared with those with an ulcer diameter > 1 cm, irrespective of treatment group. There was no difference in recurrence rate, duration of pain or the time lost because of the disease. Moderate or severe side-effects were found in 8.9% in AMT group and 6.5% in OA group. The cost of treatment for ulcer healing, H. pylori eradication and reduction in ulcer recurrence were all lower in the AMT group than in the OA group. Sensitivity analysis supported the result that AMT was more cost effective than OA. CONCLUSIONS: The AMT therapy was more effective and less costly than the OA therapy, especially in patients with H. pylori-related duodenal ulcers < 1 cm diameter.     

Effect of triple therapy (antibiotics plus bismuth) on duodenal ulcer healing. A randomized controlled trial.

OBJECTIVE: To determine whether antimicrobial therapy for Helicobacter pylori infection accelerates the healing of duodenal ulcers. DESIGN: Single-blind, randomized, controlled trial. SETTING: Veterans Affairs hospital. PARTICIPANTS: One hundred and five patients with endoscopically verified duodenal ulcers. INTERVENTION: Patients received either ranitidine, 300 mg/d, or ranitidine, 300 mg/d, plus "triple therapy" (2 g/d of tetracycline, 750 mg/d of metronidazole, and 5 or 8 bismuth subsalicylate tablets per day). Triple therapy was administered for only the first 2 weeks of ulcer treatment. MEASUREMENTS: Videoendoscopic assessment of ulcer status was done until ulcer healing was complete. Evaluations were done after 2, 4, 8, 12, and 16 weeks of therapy. MAIN RESULTS: Ulcer healing was more rapid in patients receiving ranitidine plus triple therapy than in patients receiving ranitidine alone (P less than 0.01). The cumulative percentages of patients with healed ulcers in the group receiving ranitidine plus triple therapy and in the group receiving ranitidine alone were as follows: 37% and 18% after week 2; 74% and 53% after week 4; 84% and 68% after week 8; 96% and 80% after week 12; and 98% and 84% after week 16. CONCLUSION: Combined therapy with anti-H. pylori agents and ranitidine was superior to ranitidine alone for duodenal ulcer healing. Our results indicate that H. pylori plays a role in duodenal ulcer disease.     

Triple therapy for 7 days vs. triple therapy for 7 days plus omeprazole for 21 days in treatment of active duodenal ulcer with Helicobacter pylori infection: A double blind placebo controlled trial

BACKGROUND: The current treatment for active duodenal ulcer implies a 4 weeks course with anti-secretory drugs and two antibiotics for 7 to 10 days in the case of Helicobacter pylori infection. AIM: To establish whether triple therapy with omeprazole given for 7 days with two antibiotics eradicates H. pylori, heals and prevents ulcer recurrence. PATIENTS AND METHODS: A total of 103 patients with active duodenal ulcer and H. pylori were randomly divided into: a group of 50 patients treated with omeprazole, clarithromycin and tinidazole for 7 days followed by omeprazole for 21 days, and a group of 53 patients who received the same treatment as the previous group, followed by placebo for 21 days. Endoscopy with quick urease test, histology and culture was performed at entry and after 4 and 16 weeks. RESULTS: Ulcer healing rate after 16 weeks' treatment was 95% in the former and 96% in the latter group (ns). Eradication after 16 weeks was 84% in the former and 83% in the latter group (ns). At 56 weeks, all patients examined were ulcer free and without H. pylori. CONCLUSION: Omeprazole, clarithromycin and tinidazole for 7 days heals active duodenal ulcer and eradicates H. pylori infection in most patients. Treatment extension with omeprazole, for 3 weeks, after triple therapy does not modify healing and eradication rates.     

Cure of Helicobacter pylori-positive active duodenal ulcer patients: a double-blind, multicentre, 12-month study comparing a two-week dual vs a one-week triple therapy. GISU (Interdisciplinary Group for Ulcer Study).

AIMS: To compare a two-week dual therapy to a one-week triple therapy for the healing of duodenal ulcer and the eradication of the Helicobacter pylori infection. PATIENTS AND METHODS: A total of 165 patients with active duodenal ulcer were enrolled in the study. At entry, endoscopy, clinical examination and laboratory tests were performed. Histology and the rapid urease test were used to diagnose Helicobacter pylori infection. Patients received either lansoprazole 30 mg plus amoxycillin 1 g bid for two weeks (two-week, dual therapy) or lansoprazole 30 mg plus amoxycillin 1 g plus tinidazole 500 mg bid for one week plus lansoprazole qd for an additional week (one-week, triple therapy). Two and twelve months after cessation of therapy, endoscopy and clinical assessments were repeated. RESULTS: Duodenal ulcer healing and Helicobacter pylori eradication were both significantly greater (p<0.0001) in the triple therapy group (healing: 98.6%; Helicobacter pylori cure rate: 72.6%) than in the dual therapy group (healing: 77.3%; Helicobacter pylori cure rate: 33.3%). Ulcers healed more frequently in Helicobacter pyloricured than in Helicobacter pylori-not cured patients (94.9% vs. 77.2%; p<0.0022). After one year, Helicobacter pylori eradication was re-confirmed in 46/58 patients previously treated with the triple therapy and in 10/40 patients treated with the dual therapy [p<0.0001]. Only three duodenal ulcer relapses were observed throughout follow-up: all were in Helicobacter pylori-not cured patients. CONCLUSIONS: Triple therapy was more effective than dual both in curing Helicobacter pylori infection and healing active duodenal ulcers. The speed of ulcer healing obtained after only 7 days of antibiotics and 14 days of proton pump inhibitors confirmed that longer periods of anti ulcer therapy were not necessary. Helicobacter pylori -not cured patients had more slowly healing ulcers which were more apt to relapse when left untreated.     

Eradication of helicobacter pylori reduces the rate of duodenal ulcer rebleeding: a long-term follow-up study

Objectives: The long-term efficacy of Helicobacter pylori eradication to reduce the rate of recurrence of peptic ulcer bleeding is still uncertain. We evaluated the rate of duodenal ulcer rebleeding for 48 months after H. pylori eradication.
Methods: Thirty-two male patients with H. pylori infection and duodenal ulcer bleeding were treated with omeprazole (40 mg/day for 4 wk), colloidal bismuth (480 mg/day for 2 wk), amoxicillin (2 g/day for 1 wk), and metronidazole (750 mg/day for 1 wk), and followed up for 48 months. Endoscopy and tests for H. pylori infection were repeated every year.
Results: Ulcer healed in all patients, but H. pylori infection persisted or recurred in 11 patients. Within 48 months, rebleeding occurred in nine (81.8%) of these patients, whereas the 21 patients who were persistently negative for H. pylori infection remained asymptomatic without rebleeding (0/21 = 0%,   p < 0.002  ) during the whole follow-up.
Conclusions: Eradication of H. pylori can reduce the rate of duodenal ulcer rebleeding for at least 4 yr, thus potentially modifying the natural history of the disease.     

Role of Helicobacter pylori in ulcer healing and recurrence of gastric and duodenal ulcers in longterm NSAID users. Response to omeprazole dual therapy.

BACKGROUND: The relation between Helicobacter pylori infection and non-steroidal anti-inflammatory drug (NSAID)-associated peptic ulcers remains unclear; in particular, it is not known whether H pylori plays a part in the healing and recurrence of these ulcers. AIMS: To evaluate prospectively in a consecutive series of arthritis patients receiving longterm NSAID treatment the prevalence of peptic ulcer as well as the effect of H pylori eradication on the healing and recurrence of gastric and duodenal ulcer found. PATIENTS: Some 278 consecutive patients underwent gastroscopy with multiple biopsies of the gastric antrum and corpus for histological examination and rapid urease test. One hundred peptic ulcers (59 gastric ulcers, 39 duodenal ulcers, and two gastric ulcers concomitant with a duodenal ulcer) were found. Seventy per cent of these ulcers were H pylori positive. METHODS: According to their H pylori status, ulcer patients were randomised to one of the following treatments: H pylori negative ulcers received omeprazole 20 mg twice daily for four to eight weeks, whereas H pylori positive lesions were treated with omeprazole 20 mg twice daily plus amoxycillin 1 g twice daily (the second of these for the first two weeks) or omeprazole alone for four to eight weeks while continuing NSAID therapy. Patients with healed ulcers were endoscopically followed up for six months after stopping antiulcer therapy while continuing NSAIDs. RESULTS: Endoscopic healing rates for gastric and duodenal ulcers in the three different groups were similar both at four and eight weeks. H pylori eradication did not influence healing, which occurred in 14 of 20 (70%) of patients in whom H pylori was eradicated, compared with 14 of 17 (82%) of patients with persistent infection. Cumulative recurrence rates at six months did not statistically differ among the three different groups (27% in H pylori negative, 46% in H pylori positive, and 31% in those where H pylori was eradicated during the healing phase), although a numerical trend in favour of a higher recurrence rate in infected patients was evident. CONCLUSIONS: H pylori eradication does not confer any significant advantage on the healing of gastric and duodenal ulcers associated with longterm NSAID use. It remains to be established with certainty whether eradication may be helpful in the reduction of recurrence in a specific subset of NSAID associated ulcer.     

Twice-daily, 10-day triple therapy with omeprazole, amoxicillin, and clarithromycin for Helicobacter pylori eradication in duodenal ulcer disease: results of three multicenter, double-blind, United States trials

Objective: We assessed the safety and efficacy of 10-day twice-daily triple therapy for Helicobacter pylori ( H. pylori ) in three double-blind, controlled trials in patients with duodenal ulcer disease.
Methods: H. pylori -infected patients with one or more duodenal ulcer(s) at endoscopy (studies 1, 2) or with a documented duodenal ulcer history and no duodenal ulcer or erosions at endoscopy (study 3) were randomly assigned to 10-day courses of omeprazole 20 mg b.i.d . plus amoxicillin 1 g b.i.d . plus clarithromycin 500 mg b.i.d . (OAC) or placebo plus amoxicillin 1 g b.i.d . plus clarithromycin 500 mg b.i.d . (AC). In studies 1 and 2, patients received an additional 18 days of omeprazole 20 mg q.d . (OAC group) or placebo (AC group). Endoscopy was repeated 4 wk after therapy in studies 1 and 2 and 4–6 wk after therapy in study 3. At baseline, H. pylori was diagnosed by CLOtest plus histology, or by culture. Eradication was defined as no positive biopsy test and two or more negative tests. Patients were defined as compliant if they took 75% or more of each study drug and missed ≤ 3 consecutive days of the 10-day therapy.
Results: Intent-to-treat populations of the three studies combined were 241 patients for OAC and 266 for AC. Of all OAC patients combined, 2% stopped study medications due to adverse events, and 93% were compliant. Per-protocol cure rates were 78% to 90% (all studies combined, 84%) for OAC vs 33% to 45% (combined, 39%) for AC (   p < 0.001  , OAC vs AC); intent-to-treat eradication rates were 69% to 83% (combined, 75%) for OAC vs 32% to 37% (combined, 35%) for AC; (   p < 0.001  , OAC vs AC).
Conclusion: Rigorously designed studies indicate that 10 days of twice-daily triple therapy with omeprazole, amoxicillin, and clarithromycin achieves per-protocol eradication rates of approximately 80% to 90% in the U.S.