Eradication of Helicobacter pylori and prevention of recurrence of duodenal ulcer: a randomized, double-blind, multi-centre trial of omeprazole with or without clarithromycin

Background: Antimicrobial treatment for Helicobacter pylori eradication is currently recommended for all patients with duodenal ulcer disease, but consensus on the best treatment is lacking. Methods: Patients with active duodenal ulcer and H. pylori were enrolled in a double-blind, randomized, placebo-controlled multi-centre study. Patients received omeprazole 40 mg daily for 28 days and either clarithromycin 500 mg t.d.s. or placebo t.d.s. for the first 14 days. Patients underwent endoscopy before starting treatment, at 2 weeks, immediately after stopping treatment if unhealed at 2 weeks, and at 1, 6 and 12 months after the end of treatment, or at the recurrence of symptoms. Eradication of H. pylori, duodenal ulcer healing and ulcer recurrence were measured. Results: One-hundred and fifty-four patients were recruited and randomized to omeprazole plus clarithromycin (n= 74) or to omeprazole plus placebo (n= 80). One month after treatment, H. pylori was eradicated in 57 of 69 (83%; 95% CI: 72–91%) patients receiving omeprazole plus clarithromycin, compared with 1 of 75 (1%; 95% CI: 0–7%) receiving omeprazole alone (P < 0.001). In patients receiving omeprazole plus clarithromycin the ulcer healed at 2 weeks in 83% (95% CI: 71–91%) and at 4 weeks in 100% (95% CI: 95–100%), compared with 77% (95% CI: 66–86%) and 97% (95% CI: 91–100%) in those given omeprazole plus placebo (N.S.). Ulcers recurred at 12 months in 6% (95% CI: 1–16%) of patients given omeprazole plus clarithromycin, compared with 76% (95% CI: 63–86%) of patients given omeprazole plus placebo (P < 0.001). The incidence of side-effects was similar in both treatment groups (38% with clarithromycin dual therapy and 29% with omeprazole plus placebo; P= 0.304). Ninety per cent of patients took at least 90% of their prescribed medication. Conclusions: Omeprazole plus clarithromycin dual therapy eradicated H. pylori in 83% of patients with duodenal ulcer and significantly decreased 12-month recurrence from 76% to 6%.     

Clinical trial: prolonged beneficial effect of Helicobacter pylori eradication on dyspepsia consultations – the Bristol Helicobacter Project

Aliment Pharmacol Ther 2010; 32: 394–400

Summary

Background Chronic infection of the stomach with Helicobacter pylori is widespread throughout the world and is the major cause of peptic ulcer disease and gastric cancer. Short‐term benefit results from community programmes to eradicate the infection, but there is little information on cumulative long‐term benefit. Aim To determine whether a community programme of screening for and eradication of H. pylori infection produces further benefit after an initial 2‐year period, as judged by a reduction in GP consultations for dyspepsia. Methods A total of 1517 people aged 20–59 years, who were registered with seven general practices in Frenchay Health District, Bristol, had a positive ¹³C‐urea breath test for H. pylori infection and were entered into a randomized double‐blind trial of H. pylori eradication therapy. After 2 years, we found a 35% reduction in GP consultations for dyspepsia (previously reported). In this extension to the study, we analysed dyspepsia consultations between two and 7 years after treatment. Results Between two and 7 years after treatment, 81/764 (10.6%) of participants randomized to receive active treatment consulted for dyspepsia, compared with 106/753 (14.1%) of those who received placebo, a 25% reduction, odds ratio 0.84 (0.71, 1.00), P = 0.042. Conclusions Eradication of H. pylori infection in the community gives cumulative long‐term benefit, with a continued reduction in the development of dyspepsia severe enough to require a consultation with a general practitioner up to at least 7 years. The cost savings resulting from this aspect of a community H. pylori eradication programme, in addition to the other theoretical benefits, make such programmes worthy of serious consideration, particularly in populations with a high prevalence of H. pylori infection.     

Omeprazole or ranitidine bismuth citrate triple therapy to treat Helicobacter pylori infection: a randomized, controlled trial in Vietnamese patients with duodenal ulcer

Aim:

To evaluate the effectiveness of triple therapy containing either omeprazole or ranitidine bismuth citrate (RBC) to treat H. pylori infection in Vietnamese duodenal ulcer patients.

Methods:

Patients infected with H. pylori were randomized to receive either omeprazole (20 mg b.d.), clarithromycin (500 mg b.d.) and amoxycillin (1 g b.d.) for 10 days (OAC), or RBC (400 mg b.d.), clarithromycin (500 mg b.d.) and amoxycillin (1 g b.d.) for 10 days (RAC). H. pylori eradication and ulcer healing was established by a follow‐up oesophagogastroduodenoscopy (EGD) at least 4 weeks after therapy. Side‐effects and compliance were assessed.

Results:

One hundred and four out of 108 (96%) patients with a duodenal ulcer were infected with H. pylori. Eighty per cent of infected patients had detectable CagA IgG antibodies. Fifty‐seven patients received OAC and 47 received RAC. OAC eradicated H. pylori in 91 and 86% of patients by per protocol (PP) and intention‐to‐treat (ITT) analysis, respectively. PP and ITT eradication rates for RAC were 96 and 91%. Ulcer healing at the follow‐up EGD was 89% with OAC and 100% with RAC. Side‐effects were minor. No patient failed to complete the protocol due to side‐effects.

Conclusion:

Triple therapy with either omeprazole or RBC is highly effective in eradicating H. pylori and healing duodenal ulcer in Vietnamese patients.

     

There are some benefits for eradicating Helicobacter pylori in patients with non-ulcer dyspepsia

Background

: The relationship between Helicobacter pylori infection and non‐ulcer dyspepsia is not established.

Aim

: To determine whether eradication of H. pylori might be of benefit in non‐ulcer dyspepsia patients.

Methods

: We randomly assigned 129 H. pylori infected patients with severe epigastric pain, without gastro‐oesophageal reflux symptoms, to receive twice daily treatment with 300 mg of ranitidine, 1000 mg of amoxicillin, and 500 mg of clarithromycin for 7 days and 124 such patients to receive identical‐appearing placebos.

Results

: Treatment was successful (decrease of symptoms at 12 months) in 62% of patients in the active‐treatment group and in 60% of the placebo group (N.S.). At 12 months, the rate of eradication of H. pylori was 69% in the active‐treatment group and 18% in the placebo group (P < 0.001). Complete relief of symptoms occurred significantly more frequently in patients on the active treatment (43%) than in placebo‐treated patients (31%, P=0.048). Within the active‐treatment group, therapeutic success was significantly more frequent in the non‐infected patients (84% vs. 64%, P=0.04).

Conclusions

: Although eradicating H. pylori is not likely to relieve symptoms in the majority of patients with non‐ulcer dyspepsia, a small proportion of H. pylori‐infected patients may benefit from eradication treatment.

     

Randomised clinical trial: Helicobacter pylori eradication is associated with a significantly increased body mass index in a placebo-controlled study

Aliment Pharmacol Ther 2011; 33: 922–929

Summary

Background Body mass index (BMI) increased following Helicobacter pylori eradication in several Japanese cohorts, which requires further investigation. Aim To determine the impact of H. pylori eradication on BMI in a European population. Methods A total of 10 537 unselected people aged 20–59 years were screened for H. pylori; 1558 of the 1634 infected participants were randomised to intervention (eradication therapy: ranitidine bismuth citrate 400 mg and clarithromycin 500 mg twice daily) or placebo for 2 weeks with follow‐up at 6 months (92%) for weight and dyspepsia symptoms (epigastric pain). Results The mean weight of participants in the intervention group increased from 77.7 kg at baseline to 78.4 kg at 6 months (unadjusted increase of 0.7 kg) and from 76.8 to 77.2 kg (0.5 kg) in the placebo group. The adjusted difference between randomised groups was statistically significant at 0.6 kg [95% confidence interval (CI) 0.31, 0.88]. Significantly, more participants gained ≥3 kg in the intervention group (138/720, 19%) compared with the placebo group (92/706, 13%) [odds ratio (OR) 1.57 (95% CI: 1.17, 2.12)]. The mean BMI increased from 27.5 to 27.8 kg/m² at 6 months in the intervention group compared with the increase from 27.0 to 27.2 kg/m² in the placebo group [adjusted difference between groups was statistically significant at 0.2 kg/m² (95% CI: 0.11, 0.31)]. Dyspepsia was less frequently reported by intervention group participants (168/736, 23%, placebo group 209/711, 29%), OR 0.71 (95% CI: 0.55, 0.93). Conclusion Body mass index increased significantly following randomisation to H. pylori eradication therapy, possibly due to resolution of dyspepsia.     

Effective treatment after failure of omeprazole plus amoxycillin to eradicate Helicobacter pylori infection in peptic ulcer disease

Methods: Fifty patients with relapsing or complicated Helicobacter pylori positive duodenal (n= 41) or gastric ulcer disease (n= 9) and failure of a combined treatment with omeprazole plus amoxycillin to eradicate H. pylori infection were re-treated with either oral triple therapy (bismuth subsalicylate, metronidazole, tetracycline) plus ranitidine [group I: n= 22] or high-dose omeprazole (40 mg b.d. to t.d.s.) plus amoxycillin (1 g t.d.s.) [group II: n= 28]. Results: Patients of group I and II had similar demographic and clinical characteristics. The overall proportion of eradication of H. pylori infection was 81.8% in group I and 78.6% in group II (P= N.S.) as judged from negative bacterial findings by means of an urease test, specific culture and histology after modified Giemsa stain. Ulcer healing was observed in all patients after a maximum duration of 10 weeks. Ten patients on triple therapy and only one patient on omeprazole plus amoxycillin (45.5%vs. 3.6%; P < 0.001) complained of side effects without necessity of discontinuation of the study medication in either group. Twenty patients (group I: n= 10: group II: n= 10) with relapsing duodenal ulcer disease and successful cure were prospectively followed for one year without any evidence of ulcer relapse or H. pylori re-infection. Conclusion: Oral triple therapy plus ranitidine or highdose omeprazole plus amoxycillin remain highly effective in eradicating H. pylori infection in patients with peptic ulcer disease and treatment failure of omeprazole/amoxycillin, but the omeprazole enhanced antibiotic monotherapy seems to be superior with regard to side effects. Thus, high-dose omeprazole/amoxycillin is recommended as the treatment of first choice in these selected patients. Triple therapy should be reserved for patients intolerant of amoxycillin     

The efficacy,safety and tolerability of pantoprazole-based one-week triple therapy in H. pylori eradication and duodenal ulcer healing

SUMMARY

Objective: Recently, proton pump inhibitor (PPi)-based triple therapy has been recommended as a first line treatment in the eradication of Helicobacter pylori. The aim of this open, multicentre trial was to investigate the efficacy, safety, tolerability and the ulcer healing rate of a triple regimen consisting of pantoprazole^? 40?mg, clarithromycin 500?mg and amoxicillin 1000?mg twice daily for 7?days, in the eradication of H. pylori in patients with duodenal ulcer in Turkey.

Research design and methods: H. pylori infection was assessed by histological examination and rapid urease test at baseline and 4?weeks after the completion of the therapy. Seventy-seven patients were enrolled, 5 were excluded due to various reasons and 72 completed the entire course of the trial.

Results: H. pylori eradication was confirmed in 49 of these patients; the eradication rate was 68% by per-protocol analysis and 63.6% by intention-to-treat analysis. The ulcers were completely healed in 61 patients (85%) at the second endoscopic examination. Drug compliance was excellent (97.3%) and there were no serious adverse events.

Conclusion: Pantoprazole-based 1-week triple therapy was well tolerated and the ulcer healing rate was high (85%). Relatively low H. pylori eradication rates may be attributed to rising antibiotic resistance over recent years. A large scale, comparative study with other PPi-based regimens is warranted based on the results of this open study with the pantoprazole-based regimen.     

Addition of metronidazole to omeprazole/amoxycillin dual therapy increases the rate of Helicobacter pylori eradication: a double-blind, randomized trial

Aims: To compare the efficacy, safety and tolerability of an omeprazole/amoxycillin (OA) dual therapy Helicobacter pylori eradication regimen with an omeprazole/amoxycillin/metronidazole (OAM) triple therapy regimen. Methods: In this double-blind trial, conducted in 19 hospitals, 119 patients with symptomatic duodenal ulcer disease were randomized to receive either 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and placebo followed by a further 14 days’treatment with omeprazole 20 mg daily (n= 59) or 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s., followed by a further 14 days’treatment with omeprazole 20 mg daily (n= 60). H. pylori status was assessed by ¹³C-urea breath test at entry and at 4 weeks post-treatment. Results: H. pylori infection was eradicated in 46% of the OA treated patients and in 92% of the OAM treated patients, a mean difference of 46% (P < 0.0001, 95% CI for the difference: + 30 to + 62). In only one patient was the duodenal ulcer not endoscopically healed after 4 weeks of treatment (OA 100%; OAM 98% healed). There were no significant differences in speed of symptom relief or improvement in symptoms between the two groups. Both regimens were well tolerated, with 96% of patients completing the course, and only one patient withdrawing due to an adverse event. The only side-effect with a significantly higher incidence in the OAM group was diarrhoea, which occurred in 36% of patients compared to 16% of patients in the OA group (P < 0.05). Conclusions: A regimen consisting of omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. for 14 days gives an appreciably higher H. pylori eradication rate than omeprazole and amoxycillin alone, with acceptable tolerability.     

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.

     

Incidence of duodenal ulcer healing after 1 week of proton pump inhibitor triple therapy for eradication of Helicobacter pylori

Background:

A number of clinical studies have assessed the efficacy of short-term twice-daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens.

Aim:

To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease.

Methods:

Following endoscopic confirmation of duodenal ulcer disease and a positive CLO test, patients underwent a ¹³C-urea breath test to confirm H. pylori status. Treatment with one of four regimens: LAC, LAM, LCM or OAM, where L is lansoprazole 30 mg b.d., A is amoxycillin 1 g b.d., M is metronidazole 400 mg b.d., C is clarithromycin 250 mg b.d., and O is omeprazole 20 mg b.d., was assigned randomly to those patients who were H. pylori positive, with 62 (LAC), 64 (LAM), 61 (LCM) and 75 (OAM) patients in each treatment group. Follow-up breath tests and endoscopies were performed at least 28 days after the end of treatment.

Results:

Duodenal ulcer disease was healed 28 days after treatment in 53/62 (85.5%) patients who were treated with LAC, 52/64 (81.3%) of patients treated with LAM, 49/61 (80.3%) of patients treated with LCM and 60/75 (80.0%) of patients treated with OAM (intention-to-treat analysis, n=262, assumed unhealed if no follow-up endoscopy was performed). All the treatments were of similar efficacy (P=0.85, chi-squared test) with regard to the healing of duodenal ulcer disease.

Conclusions:

The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.

     

Review article: common misconceptions in the management of Helicobacter pylori-associated gastric MALT-lymphoma

Aliment Pharmacol Ther 2011; 34: 1047–1062

Summary

Background Helicobacter pylori infection is the main cause of gastric mucosa‐associated lymphoid tissue (MALT) lymphoma. Aim To review several common misconceptions in the management of H. pylori‐associated gastric MALT‐lymphoma. Methods Bibliographical searches were performed in MEDLINE up to June 2011. Results If adequate diagnostic methods are used, and if only low‐grade lymphomas are considered, the prevalence of H. pylori infection is very high (almost 90%). H. pylori eradication is effective in treating approximately 80% of patients with early stage lymphoma. In H. pylori‐positive gastric high‐grade lymphomas, antibiotic therapy should always be prescribed, as approximately 50% of them regress after H. pylori eradication. Patients with early stage MALT lymphoma negative for H. pylori might still benefit from antibiotic treatment as the sole treatment. Complete remission of gastric MALT lymphoma after H. pylori eradication can take even >12 months. PCR assay for the detection of monoclonal B cells remains positive in many cases after complete remission has been reached. Patients with a persistent clonal band should not be treated unless the lymphoma can be histologically demonstrated. Synchronous occurrence of gastric adenocarcinoma and MALT lymphoma has been repeatedly reported. In some patients in complete remission, eradication of H. pylori does not prevent later development of early gastric cancer. Gastric lymphoma recurrence occurs in some patients after both bacterial and lymphoma regression. H. pylori reinfection does not constitute a prerequisite for lymphoma recurrence. Conclusions The present article states several misconceptions in the management of H. pylori‐associated gastric MALT‐lymphoma in clinical practice, reviews the related scientific evidence and proposes the adequate attitude in each case.     

Delayed Healing of Chronic Gastric Ulcer after Helicobacter pylori Infection in Mice

It has been suggested that there is a close relationship between Helicobacter pylori and the onset or recurrence of gastroduodenal disease. The aim of this study was to examine the effect of H. pylori on the healing of chronic gastric ulcers induced in mice. H. pylori administered to nude mice delayed the healing of experimental acetic acid-induced gastric ulcers. Histological examination showed the occurrence of high densities of H. pylori on the surface of epithelial cells and in the ulcerated area. Repeated administration of amoxicillin (10 mg kg ^?1 daily for 5 days) eradicated H. pylori and increased the rate of healing of gastric ulcers in H. pylori-infected mice, but metronidazole, which also eradicated the organisms, did not significantly affect the rate of healing. In conclusion, H. pylori-infection delayed the healing of gastric ulcers induced by the serosal application of acetic acid in mice, possibly by aggravation or prolongation of the mucosal inflammation. Amoxicillin eradicated H. pylori and promoted gastric ulcer healing in mice infected with H. pylori.     

Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study

Background:

Despite the widely accepted view that Helicobacter pylori is the most important cause of peptic ulcer disease, recent studies have suggested that the microbe protects against nonsteroidal anti-inflammatory drug (NSAID)-associated gastroduodenal lesions and promotes ulcer healing. We investigated the effects of H. pylori eradication on the healing of NSAID-associated bleeding peptic ulcers.

Methods:

Chronic NSAID users presenting with peptic ulcer haemorrhage underwent endoscopy to secure haemostasis and to document H. pylori infection by rapid urease test and culture. They were prospectively randomized to receive either omeprazole (20 mg once daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, all given four times daily) plus omeprazole (20 mg once daily) for 8 weeks. Endoscopy was repeated after 8 weeks. Final H. pylori status was determined by a ¹³C-urea breath test that was performed at least 4 weeks after discontinuation of omeprazole.

Results:

195 H. pylori-infected NSAID users, complicated by bleeding ulcers, were randomized to receive omeprazole alone (102) or triple therapy plus omeprazole (93). 174 patients returned for second endoscopy at 8 weeks (91 in the omeprazole group, 83 in the triple therapy group). Urea breath test was negative in 14% in the omeprazole group vs. 92% in the triple therapy group (P < 0.001). Complete ulcer healing was achieved in 88 (97%) patients in the omeprazole group and 77 (93%) in the triple therapy group (P = 0.31). On intention-to-treat analysis, ulcers were healed in 86% of the omeprazole group and 83% of the triple therapy group (P = 0.50). There was no significant difference in the healing rates of gastric or duodenal ulcers between the two groups.

Conclusion:

Eradication of H. pylori did not impair the healing of NSAID-associated bleeding peptic ulcers.

     

Lansoprazole and secnidazole with clarithromycin, amoxycillin or pefloxacin in the eradication of Helicobacter pylori in a developing country

Background:

A number of triple drug regimens using proton pump inhibitors and two antibiotics have been evaluated in the West and reported to achieve Helicobacter pylori eradication rates of over 90%. In developing countries however, these combinations have neither been well evaluated, nor the optimum treatment for H. pylori infection well defined.

Aim:

To compare the combination of a proton pump inhibitor with a nitroimidazole and another antibiotic in eradicating H. pylori infection and healing duodenal ulcer.

Methods:

Sixty consecutive patients with active duodenal ulcer who were positive for H. pylori (by rapid urease test and ¹⁴C-urea breath test) were randomized into three treatments groups: (1) LAS (n = 21): lansoprazole 30 mg o.m., amoxycillin 500 mg q.d.s. and secnidazole 2 g on alternate days for 2 weeks; (2) LCS (n = 18): lansoprazole 30 mg o.m., clarithromycin 500 mg b.d. and secnidazole 2 g on alternate days for 1 week; (3) LPS (n = 21): lansoprazole 30 mg o.m., pefloxacin 400 mg o.m. and secnidazole 2 g on alternate days for 2 weeks. Urease and breath tests were performed at 0, 6 and 12 weeks to check for H. pylori eradication.

Results:

Intention-to-treat eradication rates were as follows: LAS 86%, LCS 83%, LPS 71%; the overall ulcer healing rate was 90% at 6 weeks.

Conclusions:

High H. pylori eradication rates were achieved using the amoxycillin- and clarithromycin-based therapies. Fewer side-effects, better compliance and low cost favoured the amoxycillin-based therapy.

     

Empirical rescue therapy after Helicobacter pylori treatment failure: a 10-year single-centre study of 500 patients

Background Several ‘rescue’ therapies have been recommended to eradicate Helicobacter pylori, but they still fail in >20% of the cases, and these patients constitute a therapeutic dilemma. Aim To evaluate the efficacy of different ‘rescue’ therapies empirically prescribed during 10 years to 500 patients in whom at least one eradication regimen had failed to cure H. pylori infection. Methods Design : Prospective single‐centre study. Patients : Consecutive patients in whom at least one eradication regimen had failed. Intervention : Rescue regimens included: (i) quadruple therapy with omeprazole–bismuth–tetracycline–metronidazole; (ii) ranitidine bismuth citrate–tetracycline–metronidazole; (iii) omeprazole–amoxicillin–levofloxacin; and (iv) omeprazole–amoxicillin‐rifabutin. Antibiotic susceptibility was unknown (rescue regimens were chosen empirically). Outcome : Eradication was defined as a negative ¹³C‐urea breath test 4–8 weeks after completing therapy. Results Five hundred patients were included (76% functional dyspepsia, 24% peptic ulcer). Compliance rates with first‐, second‐ and third‐line regimens were 92%, 92%, and 95%, respectively. Adverse effects were reported by 30%, 37%, and 55% of the patients receiving second‐, third‐, and fourth‐line regimens. Overall, H. pylori cure rates with the second‐, third‐, and fourth‐line rescue regimens were 70%, 74%, and 76%, respectively. Cumulative H. pylori eradication rate with four successive treatments was 99.5%. Conclusion It is possible to construct an overall treatment strategy to maximize H. pylori eradication, on the basis of administration of four consecutive empirical regimens; thus, performing bacterial culture even after a second or third eradication failure may not be necessary.     

GR122311X (ranitidine bismuth citrate), a new drug for the treatment of duodenal ulcer

Background: Ranitidine bismuth citrate (GR122311X) is a new drug which offers potential benefits in healing duodenal ulcers and prevention of relapse. Methods: This randomized, multi-centre double-blind study of 1620 patients compared the effect of 4 weeks of treatment with GR122311X 200 mg b.d. (n= 401), 400 mg b.d. (n= 404) or 800 mg b.d. (n= 404) or ranitidine hydrochloride 150 mg b.d. (n= 411) on the rates of duodenal ulcer healing and of overall success (ulcers healed and remaining ulcer free in the 24-week follow-up phase). Results: All four treatments were equally effective at ulcer healing (79%, 85%, 84% and 81% of patients, respectively). GR122311X 400 mg b.d. (38%) and 800 mg b.d. (37%) were significantly more effective than ranitidine hydrochloride 150 mg b.d. (32%) with respect to overall success (P = 0.050 and P = 0.030, respectively) but there was no difference with GR122311X 200 mg b.d. (31%). GR122311X caused effective, dose-related suppression of H. pylori (47%, 61% and 74%); H. pylori eradication rates were 18%, 21% and 22%. GR122311X was safe and well tolerated, with an adverse event profile similar to that of ranitidine hydrochloride 150 mg b.d. Median week 4 trough plasma bismuth levels were 1.3 ng/mL, 2.3 ng/mL and 3.3 ng/mL with GR122311X 200 mg b.d., 400 mg b.d. and 800 mg b.d. respectively. No individual plasma bismuth concentrations were of clinical concern. Conclusions: GR122311X is a safe and effective ulcer healing drug, and provides a platform on which anti-H. pylori therapy can be based.     

Short report: high-dose omeprazole and amoxycillin in the treatment of Helicobacter pylori-associated duodenal ulcer

Thirteen consecutive patients with active duodenal ulcer disease were assigned to a treatment schedule with high-dose omeprazole and amoxycillin. Duodenal ulcer was diagnosed endoscopically in all patients, at which time antral biopsies were taken for culture and histology. All were positive for Helicobacter pylori and histological gastritis. Treatment was for 2 weeks: 80 mg omeprazole daily plus 500 mg amoxycillin syrup t.d.s. in the first week, followed by 40 mg omeprazole daily in the second week. Repeat gastroscopy was performed 4 weeks after completion of treatment in all patients. Duodenal ulcer healing occurred in 4/13 patients. H. pylori eradication was achieved in 2/4 patients with healed ulcers and in 3/9 patients with persistent ulceration. This study suggests that a short period of treatment with high-dose omeprazole and amoxycillin achieves low rates of ulcer healing and H. pylori eradication.     

Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment

Aliment Pharmacol Ther 2010; 32: 1069–1079

Summary

Background Problems with currently recommended Helicobacter pylori eradication therapies include unsatisfactory eradication rates and/or therapy‐associated side effects. Aim To investigate the effects of Saccharomyces boulardii as supplementation to standard triple therapy on H. pylori eradication rates and therapy‐associated side effects. Methods The Cochrane Library, MEDLINE and EMBASE databases were searched in July 2010, with no language restrictions, for randomized controlled trials (RCTs); additional references were obtained from reviewed articles. Results Five RCTs involving a total of 1307 participants (among them only 90 children) met the inclusion criteria. Compared with placebo or no intervention, S. boulardii given along with triple therapy significantly increased the eradication rate [four RCTs, n = 915, relative risk (RR) 1.13, 95% confidence interval (CI) 1.05–1.21] and reduced the risk of overall H. pylori therapy‐related adverse effects (five RCTs, n = 1305, RR 0.46, 95% CI 0.3–0.7), particularly of diarrhoea (four RCTs, n = 1215, RR 0.47, 95% CI 0.32–0.69). There were no significant differences between groups in the risk of other adverse effects. Conclusion In patients with H. pylori infection, there is evidence to recommend the use of S. boulardii along with standard triple therapy as an option for increasing the eradication rates and decreasing overall therapy‐related side effects, particularly diarrhoea.     

Helicobacter pylori attenuates the delay in ulcer healing induced by aspirin and selective COX-2 inhibitor

Helicobacter pylori (H. pylori) and NSAIDs are recognized as major pathogenic factors in peptic ulcer disease. However, whether these two factors exert synergistic or antagonistic effects on ulcer healing has not yet been fully explained. In this study, the effects of aspirin (ASA) alone and rofecoxib, a specific prostaglandin cyclooxygenase (COX)-2 inhibitor, were compared with that of ASA and rofecoxib applied in combination with H. pylori on gastric acid secretion and healing of acetic acid ulcers in rats. The H. pylori colonization of gastric mucosa was determined by viable bacterial culture and histology. The area of ulcers was determined by planimetry, the gastric blood flow (GBF) was measured using the H₂-gas clearance method and the gastric mucosal generation of PGE₂ and plasma gastrin levels were assessed by radioimmunoassay. ASA or rofecoxib applied alone delayed significantly the healing of chronic gastric ulcers and this effect was accompanied by a marked decrease in the GBF at the ulcer margin and gastric mucosal PGE₂ generation without significant influence of gastric acid output. H. pylori that produced moderate gastric inflammation at the ulcer margin as confirmed by bacterial culture, prolonged significantly the healing of these ulcers and decreased the GBF at the ulcer margin and gastric acid output while elevating significantly the gastric mucosal PGE₂ generation and plasma gastrin levels. H. pylori attenuated significantly the ASA- and rofecoxib-induced inhibition of ulcer healing and accompanying fall in the GBF at the ulcer margin and reversed, in part, the ASA- and rofecoxib-induced alterations in PGE₂ generation. We conclude that H. pylori attenuates the delay in ulcer healing induced by ASA and rofecoxib due to enhancement in the generation of endogenous PGE₂ and gastrin release, as well as suppression of acid secretion which may limit deleterious influence of NSAID on ulcer healing.     

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.