One-week antibiotics versus maintenance acid suppression therapy for Helicobacter pylori-associated peptic ulcer bleeding

Bleeding peptic ulcer is the most important cause of upper gastrointestinal bleeding. Our aim was to compare the effect of anti-Helicobacter therapy with maintenance treatment of H2-receptor antagonist in the prevention of relapses of ulcer and bleeding. Patients with bleeding duodenal or gastric ulcers and H. pylori infection were randomized to receive either a one-week course of triple therapy with bismuth subcitrate, metronidazole, and tetracycline plus ranitidine or a six-week course of ranitidine 300 mg/day. After the ulcers healed, the antibiotic-treated patients were not given any medication, whereas the ranitidine-treated patients continued to receive a maintenance dose of 150 mg/day. One hundred twenty-six patients were randomized to receive anti-Helicobacter therapy and 124 patients to receive long-term ranitidine. H. pylori eradication was achieved in 98.2% in those who received triple therapy and 6.1% in those who received ranitidine (P < 0.0001). At the six-week follow-up, ulcer healing was documented in 88.2% in those who received triple therapy and 86.1% in those who received ranitidine (P = 0.639). Recurrent ulcer developed in nine of the ranitidine-treated patients and three of them presented with recurrent upper gastrointestinal bleeding. One patient in the antibiotic group developed recurrent ulcer without rebleeding (P = 0.01). It is concluded that eradication of H. pylori is sufficient for the prevention of recurrent bleeding ulcers.     

New one-week, low-dose triple therapy for the treatment of duodenal ulcer with Helicobacter pylori infection

BACKGROUND: Antimicrobial therapy is the recommended treatment for duodenal ulcer associated with Helicobacter pylori infection. The eradication of bismuth-based triple therapy with bismuth subcitrate, metronidazole and amoxicillin is limited by low compliance, drug resistance and side-effects. Two-week proton pump inhibitor (PPI)-based triple therapy has a higher eradication rate but is costly. This study was designed to compare the efficacy, patient compliance and cost of short-term PPI-based triple therapy with those of bismuth-based triple therapy. METHODS: Ninety patients with active duodenal ulcer disease and H pylori infection, proven with the 13C-urea breath test and CLO test (Campylobacter-like organism test) were treated randomly in three therapeutic groups: Group A, DeNol 120 mg, amoxicillin 500 mg and metronidazole 250 mg four times a day orally for 14 days; Group B, omeprazole 20 mg plus clarithromycin 500 mg twice a day and amoxicillin 500 mg four times a day for 14 days; Group C, omeprazole 20 mg, clarithromycin 250 mg and metronidazole 500 mg twice a day for seven days. Nizatidine 150 mg twice a day was given continuously following the end of anti-H pylori therapy for each group. Two months later, endoscopy, the CLO test and 13C-urea breath test were repeated to assess the eradication rate of H pylori and the ulcer-healing rate. Drug tolerance was evaluated by patients themselves by daily recording of any side-effects. RESULTS: Eighty-four patients completed the entire course of therapy and evaluation for H pylori infection. The H pylori eradication rates in Groups A, B and C were 75% (21/28), 93% (26/28) and 89% (25/28), respectively (p = 0.466). The ulcer healing rate was 86% (24/28) in Group A and 89% (25/28) in Groups B and C (p = 0.764). A total of 74 patients (88%) were free from symptoms at the end of the triple therapy. Symptom relief was faster in patients with PPI-based triple therapy (Groups B and C) (days 3 and 4) than for patients with bismuth-based triple therapy (day 5). The cost of Group C therapy was lower than that for Groups A and B. There were no major side-effects in any of the patients. CONCLUSIONS: One-week triple therapy with omeprazole, clarithromycin and metronidazole is highly effected for the eradication of H pylori. A therapeutic regime of one week's duration with lower cost, good compliance and mild side-effects may offer a good choice for treatment of duodenal ulcer associated with H pylori infection in clinical practice.     

Acid suppression with ranitidine plus oral triple therapy improves ulcer healing but not Helicobacter pylori eradication

BACKGROUND/AIMS: To evaluate whether the addition of 2 weeks of ranitidine to a 1-week oral triple therapy (OTT) regimen improved ulcer healing and H. pylori eradication. METHODOLOGY: Two hundred and eleven consecutive patients with an endoscopic diagnosis of active duodenal ulcer (DU) and a positive antrum biopsy for H. pylori were enrolled. Those attending the Hospital Vera Cruz (Group A, n=142) received a 14-day course of ranitidine (150 mg after breakfast and dinner) plus a 1-week OTT, consisting of bismuth subcitrate, (240 mg after the 3 meals), tetracycline (500 mg, 10 min before the three meals and at bedtime), and furazolidone (200 mg after breakfast and dinner). Patients from the Hospital das Clinicas (Group B, n=69) received the same OTT as Group A but without ranitidine. Patients underwent endoscopy again on average 40 days (range: 30-60 days) after completing therapy in order to assess ulcer healing and H. pylori status. RESULTS: Both schedules were equally efficient in eradicating H. pylori with 90% (128/142) eradication in group A, and 84% (58/69) in group B (p=0.2). In contrast, the addition of ranitidine to OTT improved ulcer healing when compared with OTT alone (96%, 137/142, vs. 70%, 48/69; p<0.001). CONCLUSIONS: Our results demonstrate that the association of acid suppression, obtained with 2 week ranitidine administration with OTT improved ulcer healing but did not enhance H. pylori eradication.     

Comparative effect of lansoprazole/amoxicillin with omeprazole/amoxicillin for the eradication of Helicobacter pylori in patients with duodenal ulcer

Lansoprazole, a potent antisecretory drug, possesses on an equimolar basis a 4-fold higher in vitro anti-Helicobacter pylori activity than omeprazole. In a prospective randomized study we compared lansoprazole 30 mg b.i.d. and amoxicillin 1 g b.i.d. with omeprazole 40 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days followed by lansoprazole 30 mg q.d. or omeprazole 20 mg q.d. for 14 additional days in 50 H. pylori positive duodenal ulcer patients (14f, 36m, age 27-83 [mean 43] years). H. pylori infection was diagnosed by histology (3 antral biopsies and 2 from gastric body, H & E- and Giemsa stain), rapid urease test (CLO) and culture in 39 patients, or by histology and rapid urease test in 11 patients. Control endoscopy was performed 4-6 weeks after the end of treatment. For eradication, a negative result in all 3 diagnostic modalities was required. The eradication rate was 43% (9/21 patients) in both treatment groups. 8 patients were lost to follow-up. The ulcer healing rate was 100% in both groups. Nonsmokers had a significantly higher (p = 0.026) eradication rate than smokers. No relevant adverse effects of the therapy occurred. 24 patients with persistent H. pylori infection were subsequently treated with lansoprazole 60 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days. Eradication was achieved in 5/22 (23%) patients (3/14 smokers, 2/8 nonsmokers), while 2 patients were lost to follow-up. 17 patients with persistent H. pylori infection after the second treatment received quadruple therapy consisting of metronidazole 500 mg t.i.d., tetracycline 500 mg q.i.d. bismuth-subcitrate 120 mg q.i.d. and lansoprazole 30 mg for 10 days. H. pylori eradication was achieved in 12/15 patients (80%). In conclusion, lansoprazole plus amoxicillin was equal to omeprazole plus amoxicillin in the treatment of H. pylori infected duodenal ulcer patients. Patients with eradication failure after dual therapy were successfully treated by quadruple therapy. In contrast, high dose lansoprazole and amoxicillin therapy was effective in only 23% of patients with persistent infection after standard dual therapy.     

Cost-effectiveness analysis of the eradication of Helicobacter pylori as treatment for duodenal ulcer

OBJECTIVE: To assess the cost-effectiveness of H. pylori eradication in patients with duodenal ulcer in Spain. METHODS: A decision model was used to compare the cost per cured patient and the cost per patient without recurrence in one year for four treatment strategies: 1) intermittent antisecretory therapy, 2) initial antisecretory therapy and H. pylori eradication if ulcer recurrence, 3) initial H. pylori eradication with antibiotics and antisecretory drugs, 4) antisecretory therapy followed by continuous maintenance therapy with ranitidine. Clinical variables were obtained from published studies made in Spain. RESULTS: Initial H. pylori eradication is the cheapest strategy (74,702-82,028 ptas per cured patient) and the most effective (83.3-85.2% patients without recurrence in one year). Intermittent antisecretory therapy is one of the most expensive (94,891-105,324 ptas per cured patient) and the less effective (12% patients without recurrence in one year). CONCLUSION: Initial eradication of H. pylori is the treatment of choice in patients with duodenal ulcer.     

Lansoprazole. An update of its pharmacological properties and clinical efficacy in the management of acid-related disorders

Lansoprazole is a proton pump inhibitor that reduces gastric acid secretion. It has proved effective in combination regimens for the eradication of Helicobacter pylori and as monotherapy to heal and relieve symptoms of gastric or duodenal ulcers and gastro-oesophageal reflux. After initial healing, it may be used to prevent recurrence of oesophageal erosions or peptic ulcers in patients in whom H. pylori is not the major cause of ulceration and to reduce basal acid output in patients with Zollinger-Ellison syndrome. Usual dosages are 15 to 60 mg/day, although dosages of < or = 180 mg/day have been used in patients with hypersecretory states. In patients with duodenal or gastric ulcer, short term lansoprazole monotherapy was similar to omeprazole and superior to histamine H2 receptor antagonists in achieving healing rates > 90%. Lansoprazole was as effective a component of H. pylori eradication regimens as omeprazole, tripotassium dicitrato bismuthate (colloidal bismuth subcitrate) or ranitidine. Lansoprazole was superior to ranitidine in symptom relief and healing of gastro-oesophageal reflux disease and tended to relieve symptoms more rapidly than omeprazole, although initial healing was similar. As maintenance treatment, lansoprazole was similar to omeprazole and superior to ranitidine in relieving symptoms and preventing relapse. Lansoprazole was also superior to ranitidine in healing and relieving symptoms of oesophageal erosions associated with Barrett's oesophagus; healing was maintained for a mean of 2.9 years in > or = 70% of patients. Lansoprazole was also superior to ranitidine in prophylaxis of redilatation of oesophageal strictures. After > or = 4 years of use in patients with Zollinger-Ellison syndrome, lansoprazole 60 to 180 mg/day effectively controlled basal acid output. Dosages may be reduced in some patients once healing and symptom relief has been achieved. Preliminary studies of lansoprazole in patients at risk of aspiration pneumonia or stress ulcers show promise. Although studies show lansoprazole is potentially effective in treating gastrointestinal bleeding, future studies should assess patients' H. pylori status. Lansoprazole has been well tolerated in clinical trials, with headache, diarrhoea, dizziness and nausea appearing to be the most common adverse effects. Tolerability of lansoprazole does not deteriorate with age and the drug is well tolerated in long term use (< or = 4 years) in patients with Zollinger-Ellison syndrome or reflux disease. Thus, lansoprazole is an important alternative to omeprazole and H2 receptor antagonists in acid-related disorders. In addition to its efficacy in healing or maintenance treatment, it may provide more effective symptom relief than other comparator agents.     

Age-dependent eradication of Helicobacter pylori with dual therapy

BACKGROUND: Combined treatment using an acid-inhibiting drug with antibiotics can cure Helicobacter pylori infection. However, eradication rates are highly variable, especially if a proton pump inhibitor is used with amoxycillin. Therefore it is important to define factors/predictors of the clinical outcome. METHODS: In a single-blind study, 60 H. pylori-positive patients prospectively matched for diagnosis (erosive gastritis, duodenal and gastric ulcer), age (above and below 50 years) and smoking habits were randomly treated (each group n = 20) for 2 weeks with amoxycillin (1 mg b.d.) and either omeprazole (20 mg b.d.), lansoprazole (30 mg b.d.) or ranitidine (300 mg b.d.). Intragastric pH and plasma levels of the administered drugs were monitored over a dosing interval of 12 h. RESULTS: The overall eradication rates were 45% (intention-to-treat, ITT, 27/60) or 47% (per protocol 27/58); they did not differ (ITT) between omeprazole (50%), lansoprazole (40%) and ranitidine (45%). Median pH and time at which intragastric pH was above 4 was slightly lower for ranitidine (4.0 +/- 1.7; 51 +/- 25%) than for omeprazole (5.4 +/- 1.1: 77 +/- 25%; P < 0.05) or lansoprazole (4.4 +/- 1.6: 68 +/- 32%). Plasma concentrations of amoxycillin were comparable in all three treatment groups. Post-treatment H. pylori status was not dependent on those levels, or the drug-induced extent or duration of increased intragastric pH. However, H. pylori-eradicated patients were significantly (P < 0.05) older (56 +/- 13 years) than patients still H. pylori-positive (47 +/- 14 years). In addition, in patients older than 50 years (n = 33), eradication was higher (P < 0.01) than in patients (n = 25) below 50 years (65 vs. 24%). Eradication rate was highest (75-83%) in subgroups of patients (> 50 years and history of peptic ulcer or smokers). Neither activity/grade of peptic ulcer or erosive gastritis nor initial diagnosis were predictors for clinical outcome. CONCLUSION: The age of patients must be regarded as a major determinant of H. pylori eradication rate and may represent an important factor contributing to the highly variable clinical results.     

Helicobacter pylori eradication and ulcer healing with daily lansoprazole, plus 1 or 2 weeks co-therapy with amoxycillin and clarithromycin

BACKGROUND: Proton pump inhibitor based combination therapy is one standard strategy for Helicobacter pylori eradication. AIM: To compare the eradication and duodenal ulcer healing efficacy of two 2-week, single dose, lansoprazole based combination therapies. METHODS: Healthy adult patients with endoscopically confirmed, H. pylori associated duodenal ulcer disease (3 mm > ulcer < 20 mm) were eligible for the study. All patients received a 14 day course of lansoprazole 30 mg o.m., and were randomized to receive either 7 or 14 days of amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry and 14-17 days later. Symptomatic, unhealed patients received a further 14 days of therapy with lansoprazole 30 mg o.m. Eradication was confirmed a minimum of 28 days after cessation of all therapy by urease reaction and histological assessment of gastric body and antral biopsies (three biopsies each site). RESULTS: Sixty-two patients were randomized to a treatment arm, of which 58 could be included in an intention-to-treat and key-point-available analysis. H. pylori eradication rates were identical, at 93% (95% CI: 73-98% (1 week), 78-99% (2 week)). In the combined group, all but 13 ulcers were healed at 2 weeks; six required further therapy because of symptoms, while six of the seven asymptomatic patients went on to heal. CONCLUSION: An eradication regimen, based on a 2-week course of single dose lansoprazole with 1 week of antibiotic co-therapy, is effective in eradicating H. pylori, while the 2 weeks of acid suppression is usually effective in duodenal ulcer healing.     

Omeprazole and ranitidine in long-term treatment of duodenal ulcer: a double-blind comparison of length of time in remission

In most patients duodenal ulcer is a chronic relapsing disease. If no active maintenance treatment or eradication therapy is given after healing, around 70-100% of patients have a relapse during the first year. We conducted a double-blind multicenter study in 472 patients with duodenal ulcer. They were treated with omeprazole 20 mg every morning for four or eight weeks and when healed were randomly allocated to maintenance treatment with either omeprazole 20 mg every morning or ranitidine 150 mg at bedtime for up to six months. The patients were assessed by endoscopy at monthly intervals until healing occurred. Thereafter scheduled endoscopy was carried out after 1, 3, and 6 months of maintenance treatment or immediately in the event of a suspected relapse. Healing status (intention to treat approach) was 87% at four weeks and 93% at eight weeks. At six months the estimated remission rate was 90% for omeprazole and 82% for ranitidine (P = 0.03, 95% CI 1-15%). The incidence of adverse events was similar during the two maintenance treatments. Treatment with omeprazole 20 mg every morning maintained significantly more patients in remission than treatment with ranitidine 150 mg at bedtime.     

Proposed recommendations for research on biochemical markers for problematic drinking

Successful eradication of Helicobacter pylori infection in children has required long treatment regimens that may result in noncompliance with failure to eradicate this organism. Despite full compliance with shorter therapeutic regimens, such as amoxycillin and omeprazole for 2 wk, the H. pylori eradication rate is poor in children. OBJECTIVES: The aim of this study was to evaluate the efficacy of, and compliance with, a 2-wk treatment with metronidazole, omeprazole, and clarithromycin in eradicating H. pylori disease in children. METHODS: Over a 15-month period, children diagnosed to be H. pylori positive by Steiner's stain of gastric antral biopsy specimens were treated with metronidazole, omeprazole, and clarithromycin. Follow-up upper GI endoscopy was performed 6-8 wk after completion of therapy. RESULTS: Of 15 patients with H. pylori-positive antral gastritis, 11 had duodenal ulcer disease; three patients with severe abdominal pain and one with vomiting had H. pylori gastritis only. H. pylori eradication was seen in 11 of 11 (100%) patients with duodenal ulcer disease and in three of four (75%) with gastritis only; the overall success rate was 93%. Duodenal ulcer disease healed when H. pylori was eradicated in all but one patient, who at presentation had a penetrating ulcer with a duodenobiliary fistula. Fourteen of 15 patients (93%) were fully compliant, and no adverse reactions were reported. CONCLUSIONS: Two weeks of therapy with metronidazole, omeprazole, and clarithromycin is effective H. pylori therapy in children. It is well tolerated, and full compliance can be achieved.     

One-week low-dose triple therapy vs. two-week medium-dose double therapy for H.pylori infection

BACKGROUND/AIMS: Our study is to compare a short-term low-dose triple therapy with a long-term medium-dose double therapy for H.pylori eradication. MATERIALS AND METHODS: One hundred and ten consecutive patients, suffering from dyspeptic symptoms, with H.pylori infection, were randomly allocated to one of the following 2 groups with different therapeutic regimens: A) omeprazole 20 mg/day for 7 days, tinidazole 500 mg bid for 7 days, clarithromycin 250 mg bid for 7 days (55 pts, 20 with peptic ulcer); B) omeprazole 20 mg bid for 14 days, amoxycillin 1000 mg bid for 14 days (55 pts, 28 with peptic ulcer). The "H.pylori status" was evaluated by means of histology, culture and urease test, at entry and 8 weeks after treatment. RESULTS: Two group A and one group B pts didn't complete the treatment. The H.pylori eradication was obtained in 38 pts of group A (71.69%) (C.I.95%: 55.19176-80.86293), in 31 of group B (58.49%) (C.I.95%: 42.32777-69.7017); on Intention-to-Treat analysis, the rate of eradication gave similar results. Side effects occurred in 9 pts of group A (16.98%), in 8 of group B (14.81%). CONCLUSIONS: Short-term low-dose triple therapy with omeprazole/tinidazole/clarithromycin has a better cost/benefit ratio than long-term dual therapy with omeprazole/amoxycillin in the H.pylori eradication, but it causes more side-effects.     

Triple therapy with sucralfate is not effective in eradicating Helicobacter pylori and does not reduce duodenal ulcer relapse rates

OBJECTIVES: The most used therapeutic schedule to eradicate Helicobacter pylori is the "triple therapy," which is based on the simultaneous use of a bismuth salt and two antibiotics. Sucralfate, a basic aluminum salt of sucrose sulfate, is supposed to have an antibacterial activity and is said to reduce the bacterial density of H. pylori. This randomized, prospective clinical trial compares the efficacy of an alternative oral triple therapy consisting of sucralfate, tinidazol, and tetracycline with a conventional therapy using ranitidine, with respect to H. pylori eradication and duodenal ulcer healing and recurrence in a 12-month follow-up. METHODS: Forty-three patients with active duodenal ulcers diagnosed at endoscopy were enrolled to receive either 1 g of sucralfate four times daily for 30 days, 500 mg of tetracycline four times daily, and 500 mg of tinidazol three times daily, for 10 days (group A; n = 23) or 150 mg of ranitidine twice daily for 30 days (group B; n = 20). The groups were age- and sex-matched and balanced for tobacco use and H. pylori status. Compliance assessed by post-treatment interviews was considered high (all patients declared that they had ingested at least 80% of the drugs). RESULTS: Both therapies were efficient in healing ulcers (group A, 95%; group B, 90%), the relapse rates were high in both groups (group A, 77%; group B, 89%), and the alternative triple therapy eradicated H. pylori in only 4% of the patients. CONCLUSION: Alternative oral triple therapy presented no significant advantage over ranitidine treatment of active ulcer disease.     

Helicobacter pylori eradication as a surrogate marker for the reduction of duodenal ulcer recurrence

OBJECTIVES: An abundance of data exists documenting the association of H. pylori eradication with the reduction in duodenal ulcer recurrence. AIM: To evaluate the validity of using H. pylori eradication as a surrogate marker for the reduction in duodenal ulcer recurrence using rigorously controlled studies. METHODS: Three controlled clinical trials were conducted in patients with uncomplicated, active duodenal ulcers. Patients were treated with various combinations of omeprazole and amoxycillin. Ulcer healing and H. pylori eradication were assessed. For patients whose duodenal ulcer healed, duodenal ulcer recurrence was determined over a 6-month period in patients with H. pylori eradication and those remaining positive for H. pylori at least 4 weeks after treatment. To support the data obtained from these clinical trials, a search of the medical literature was conducted to identify additional human clinical trials in which duodenal ulcer recurrence rates were measured and categorized by H. pylori status at least 1 month post-treatment. RESULTS: In 11 controlled trials, the overall 6-18-month duodenal ulcer recurrence rate was 54% among patients remaining positive for H. pylori at least 4 weeks after treatment compared to 6% among patients with H. pylori eradication following treatment. This finding was corroborated by the uncontrolled trials, in which the duodenal ulcer recurrence rate was 64% among patients found to be H. pylori-positive and 6% for patients found to be H. pylori-negative at least 4 weeks after treatment. A time course of duodenal ulcer recurrence rates using pooled data from both controlled and uncontrolled studies demonstrated that duodenal ulcer recurrence rates for H. pylori-negative patients persisted for up to 4 years following treatment. Duodenal ulcer recurrence rates for H. pylori-positive patients increased for the first year, then levelled off. A comparison of the duodenal ulcer recurrence rates for different treatment regimens revealed that eradication regimens based on omeprazole plus antibiotics and bismuth plus antibiotics exhibited similar duodenal ulcer recurrence rates for H. pylori-positive and -negative patients. CONCLUSION: Regardless of treatment regimens, H. pylori eradication produced a consistent and significant reduction in duodenal ulcer recurrence. Therefore H. pylori eradication, 4 weeks post-therapy, can be used as a surrogate marker for reduced duodenal ulcer recurrence in investigational clinical trials.     

One-week use of ranitidine bismuth citrate, amoxycillin and clarithromycin for the treatment of Helicobacter pylori-related duodenal ulcer

BACKGROUND: Proton pump inhibitors have been widely used in combination with amoxycillin, clarithromycin or metronidazole for the treatment of Helicobacter pylori infection. AIM: To study the effects of 1-week ranitidine bismuth citrate (RBC)-based triple therapy in the treatment of H. pylori-related duodenal ulcers. METHOD: Patients with duodenal ulcers and H. pylori infection were prospectively randomized to receive either RBC with amoxycillin and clarithromycin for 1 week (RAC), or omeprazole with amoxycillin and clarithromycin for 1 week (OAC). No additional ulcer healing drug was used after the 1-week medication. Patients were assessed for H. pylori eradication, ulcer healing and side-effects after receiving the therapies. RESULTS: One hundred consecutive patients were recruited to this study, with 50 patients randomized to each treatment group. In the intention-to-treat analysis, duodenal ulcers were completely healed in 45 (90%) patients in the RAC group and 43 (89.6%) in the OAC group (P = 1.0). H. pylori eradication was confirmed in 47 (94%) in the RAC group and 42 (87.5%) in the OAC group (P = 0.31). There was no significant difference in the severity of side-effects experienced by the two treatment groups. CONCLUSION: One-week RBC-based triple therapy is an effective treatment for H. pylori-related duodenal ulcers. The therapeutic effects are comparable to a 1-week course of proton pump inhibitor-based triple therapy.     

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 < or = 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.     

Erosive duodenitis: prevalence of Helicobacter pylori infection and response to eradication therapy with omeprazole plus two antibiotics

OBJECTIVES: To study the prevalence of Helicobacter pylori infection in patients with erosive duodenitis (ED), the associated gastric histological lesions and their response to eradication therapy with omeprazole plus two antibiotics. METHODS: A prospective study was made of 57 patients with ED (mean age 46 +/- 16 years, 72% males). At endoscopy, biopsies from gastric antrum and body were obtained for histological study (haematoxylin and eosin). A 13C-urea breath test was also performed. Omeprazole 20 mg twice daily plus two antibiotics (amoxycillin 1 g twice daily, clarithromycin 500 mg twice daily, metronidazole 500 mg twice daily) were administered for 1 week. Endoscopy and breath test were repeated 1 month after completing therapy, and the breath test was performed again at 6 months. RESULTS: All patients were H. pylori positive. Overall eradication was achieved in 86% (95% CI 75-93%). Duodenal erosion healing was obtained in 45 patients (79%). Healing was achieved in 86% (CI 73-93%) of cases with successful eradication therapy, but only in 3/8 (37%; CI 8.5-75%) patients with therapy failure (P < 0.01). In the multivariate analysis, H. pylori eradication was the only variable which correlated with erosion healing (odds ratio 10; CI 2-51; P < 0.01). Histological improvement, in both the gastric antrum and body, was demonstrated when eradication was achieved (P < 0.001). Six months after diagnosis H. pylori absence was confirmed in all patients with initial therapy success (all of them asymptomatic), and infection was confirmed in the eight patients who were H. pylori positive after therapy (six of them symptomatic). At 6-month follow-up, endoscopy was normal in 6/7 H. pylori-negative patients with previously persistent ED, while erosions were still present in 4/5 H. pylori-positive patients with previously persistent ED. CONCLUSION: A high prevalence (100%) of H. pylori infection in patients with ED was observed. A 1-week twice daily therapy with omeprazole plus two antibiotics (clarithromycin plus amoxycillin or metronidazole) was very effective in H. pylori eradication, duodenal erosion healing, symptomatic improvement, and in disappearance of associated histological gastritis. These observations suggest that ED should be considered a variant form of duodenal ulcer disease and treated accordingly; that is, with H. pylori eradication therapy.     

A three-day octreotide-containing helicobacter pylori eradication therapy for cure of peptic ulcers

BACKGROUND/AIMS: Octreotide is used to arrest peptic ulcer hemorrhage. Since it has anti-secretory properties, it could also be used in Helicobacter pylori eradication therapy, to cure peptic ulcer before discharging patients from hospital. The aim of this pilot study was to determine safety and efficacy of an ultra short quadruple octreotide containing H. pylori eradication therapy in patients with peptic ulcer. METHODOLOGY: Twenty-six consecutive symptomatic H. pylori-positive patients with duodenal (n = 20) or gastric ulcer (n = 6), were treated with a three-day course of octreotide 0.3 mg/day subcutaneously, amoxicillin plus metronidazole 2 g/day orally and colloid bismuth subcitrate 480 mg/day. CLO-test, culture and crush tissue smears were performed on admission to the study, at 4 and 8 weeks post treatment. The effect of octreotide on intragastric pH (n = 10) was also investigated. RESULTS: Octreotide significantly increased the mean 24-hour intragastric pH > 3 over 68.9% of the time (37.1%-99.5%). There were no treatment side effects. Ulcer pain was abolished at between 2-12 days. By intention-to-treat 24/26(92.3%, 95% CI 82%-100%) ulcers had healed at 4 weeks. H. pylori eradication rate at 8 weeks was 88.5% (23/26) (95% CI 76%-100%). CONCLUSIONS: Our ultra-short octreotide containing quadruple therapy is a safe and effective regime in eradicating H. pylori and healing peptic ulcers. It may be a suitable therapy for hospitalized patients with peptic ulcer hemorrhage.     

Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection

BACKGROUND: We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection. METHODS: From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days: or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary. RESULTS: Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects. CONCLUSIONS: With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.     

Omeprazole, azithromycin and amoxicillin or amoxicillin plus clavulanic acid in eradication of Helicobacter pylori in duodenal ulcer disease

Treatment with omeprazole (OME), azithromycin (AZI) and amoxicillin (AMO) resulted in encouraging Helicobacter pylori cure rates in pilot and control studies. The aim of this study was to establish whether OME + AZI in combination with either AMO or ACA (amoxicillin plus clavulanic acid) are effective in curing H. pylori infection. A hundred patients with active duodenal ulcer and H. pylori infection were treated with OME (day 1-10: 2 x 40 mg/day, day 11-24: 40 mg/day, day 25-42: 20 mg/day) plus AZI 500 mg/day for the first 6 days. Patients were randomly assigned to either AMO 2 x 1000 mg/day (group A, n = 50) or ACA 2 x 1250 mg/day (group B, n = 50) during the first 10 days of treatment. H. pylori status was determined by urease test and histology before and 6 weeks after completion of therapy. Ninety-five patients completed the study. H. pylori infection was eradicated in 85.4% (41/48) patients from group A (intention-to-treat (ITT) analysis: 82%) versus 91.5% (43/47) patients from group B (ITT) analysis: 86%) (NS). All ulcer had healed after 42 days of omeprazole treatment. Side effects, usually minor, were recorded in 12.5% (group A) and 14.9% (group B) of patients (NS). Therapy had to be discontinued in two patients (one in group A and one group B) only. Ten-days treatment with OME and AZI (for the first 6 days) with AMO or ACA are simple and highly effective regimens to cure H. pylori infection in patients with duodenal ulcer disease.     

Animal model of human medulloblastoma: clinical, magnetic resonance imaging, and histopathological findings after intra-cisternal injection of MHH-MED-1 cells into nude rats

OBJECTIVES: It was our goal to evaluate the efficacy and safety and patient compliance with omeprazole-based dual and triple therapy for eradication of Helicobacter pylori in peptic ulcer disease. MATERIALS AND METHODS: One hundred seventy-five consecutive patients with H. pylori infection and associated active peptic ulcer were included. H. pylori infection was assessed by rapid urease test and histological analysis. Patients were randomized among three treatments: group 1 (56 patients): omeprazole, 20 mg bid, and amoxicillin, 1 gm bid, for 2 weeks; group 2 (61 patients): omeprazole, 20 mg bid, plus amoxicillin, 1 gm bid, and metronidazole, 500 mg bid, for 1 week; and group 3 (58 patients): omeprazole, 20 mg bid, plus amoxicillin, 1 gm bid, and clarithromycin, 500 mg bid, for 1 week. Ulcer healing and cure of infection were evaluated at 4 to 6 weeks after cessation of therapy. Eradication rate was calculated per-protocol and by an intention-to-treat analysis. RESULTS: At posttreatment endoscopy, duodenal ulcer was healed in 98.3% of patients. Eleven patients (6%) were lost to follow-up. H. pylori infection was treated successfully in 55% (95% confidence interval [CI] = 41%-69%) of patients of group 1; 86% (95% CI = 77%-95%) of group 2 (p < .001 vs. group 1); and 93% (95% CI = 85%-100%) of group 3 (p < .001 vs. group 1). On intention-to-treat analysis, eradication was 52%, 80%, and 86% in groups 1, 2, and 3, respectively. A good compliance was observed in more than 90% of patients of all groups. Side effects were reported by 7% of patients in group 1, 9% in group 2, and 11% in group 3. None of the patients stopped therapy because of side effects. CONCLUSIONS: Dual-therapy omeprazole-amoxicillin for 2 weeks is associated with significantly lower eradication rate than is 1-week omeprazole-based triple therapies. Triple therapy is well-tolerated and produces side effects similar to those of dual therapy. The highest cure rate of H. pylori infection was achieved with triple therapy of omeprazole, amoxicillin, and clarithromycin for 1 week.