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.

     

Short-term low-dose pantoprazole-based triple therapy for cure of Helicobacter pylori infection in duodenal ulcer patients

Background:

The eradication of Helicobacter pylori infection has been achieved using various therapy regimens, but the efficacy of the proton-pump inhibitor pantoprazole as part of these regimens has not yet been widely tested.

Aim:

To evaluate the efficacy and tolerability of a 1-week low-dose pantoprazole-based triple therapy in patients with H. pylori-positive duodenal ulcer.

Methods:

In an open single-centre prospective study, 71 patients with endoscopically proven active duodenal ulcer and H. pylori infection received pantoprazole 40 mg o.m. for 4 weeks, and during the first week a combination antimicrobial treatment comprising tinidazole 500 mg b.d. plus clarithomycin 250 mg b.d. H.?pylori eradication was defined as concordant negative histology and rapid urease test performed at endoscopy 4–6 weeks after the end of treatment, confirmed 4 weeks later by ¹³C-urea breath test.

Results:

Sixty-six patients (93%) completed the trial and five patients were lost to follow-up. H. pylori infection was cured in 61 out of the 66 patients who completed the trial (per-protocol analysis: 92.4%, 95% CI: 83.2–97.5%; intention-to-treat analysis: 85.9%, 95% CI: 75.7–93.0%). At final endoscopy, 65 out of 66 patients had healed ulcer (98.5%). Mild adverse events occurred in six patients (9.1%).

Conclusions:

One-week low-dose pantoprazole-based triple therapy is a simple, effective and well-tolerated regimen for ulcer healing and H. pylori eradication in patients with duodenal ulcer.

     

Comparison of omeprazole and lansoprazole in short-term triple therapy for Helicobacter pylori infection

Background:

Effective anti-Helicobacter pylori therapies with few side-effects are needed.

Aim:

To study the effectiveness of short-term triple therapy with amoxycillin, clarithromycin and either omeprazole or lansoprazole for eradication and healing of peptic ulcers.

Methods:

Patients with gastric or duodenal ulcers received amoxycillin (1 g b.d.), clarithromycin (500 mg b.d.) and lansoprazole (30 mg b.d.) (LAC) or omeprazole (20 mg b.d.) (OAC) for 7 days. Endoscopic examinations were performed before treatment and at least 4 weeks after completion of therapy. H. pylori status was confirmed by rapid urease test and histological examination (Giemsa stain) from gastric biopsies taken from both the antrum and the body.

Results:

A total of 356 patients were randomized in this single-blind study. On a per protocol basis, H. pylori was eradicated in 134 of 170 patients (79%) in the lansoprazole group and in 105 of 146 (72%) in the omeprazole group (P = 0.189); and in intention-to-treat analysis 72% and 62%, respectively (P = 0.043). Healing of the ulcers was obtained in 166 of 186 (98%), and in 139 of 146 patients (95%), respectively (P = 0.357). Side-effects occurred in two patients in the LAC group and in six in the OAC group B (four stopped therapy).

Conclusions:

This study has shown that the two regimens are highly effective in healing duodenal ulcers and are well tolerated. Neither treatment achieves the ideal cure rate for H. pylori. Lansoprazole does not appear to have a significant advantage over omeprazole either in ulcer healing or in H. pylori eradication.

     

H2-antagonist maintenance therapy versus Helicobacter pylori eradication in patients with chronic duodenal ulcer disease: a prospective study

Background:

Few outcome studies directly compare Helicobacter pylori eradication therapy with maintenance H₂-antagonist therapy in duodenal ulcer disease.

Aim:

To examine prospectively the efficacy of H. pylori eradication therapy with ranitidine maintenance therapy over 1 year in patients with confirmed chronic duodenal ulcer.

Methods:

One hundred and nineteen patients with active H. pylori infection were randomized to receive ranitidine, 150 mg/day initially (58 patients), or omeprazole, 40 mg/day, amoxycillin 2 g/day and metronidazole 1.2 g/day for 14 days, or omeprazole 40 mg/day and clarithromycin 1.5 g/day, for 14 days (if penicillin-allergic). Symptoms were assessed using the Gastro-intestinal System Rating Scale (GSRS) and SF36 quality of life index.

Results:

¹³C urea breath testing confirmed overall treatment success in 100% of patients (58/58) per protocol and 95.1% (58/61) on an intention-to-treat basis. At 4 and 12 months there were no differences in any GSRS symptoms between treatment groups. SF36 analysis showed a perceived health improvement at 4 and 12 months in patients who received H. pylori eradication. However, despite successful H. pylori eradication, one-fifth of patients still required antisecretory therapy.

Conclusion:

Following successful H. pylori eradication, chronic duodenal ulcer patients were at least as well symptomatically as when taking maintenance ranitidine. They perceived that their health had improved, but a subgroup was still acid-suppression dependent.

     

Two-week course of pantoprazole combined with 1 week of amoxycillin and clarithromycin is effective in Helicobacter pylori eradication and duodenal ulcer healing

Background:

Experience with proton pump inhibitor-based triple therapy is predominantly with omeprazole-containing regimens.

Aim:

To investigate the efficacy of a pantoprazole-based regimen, with either a 1 or 2-week course of antibiotic co-therapy, in eradicating H. pylori, healing duodenal ulcers and to assess the antibiotic sensitivity profiles of isolated H. pylori strains.

Methods:

A single-blind, multicentre, parallel group comparison of patients with endoscopically proven, H.?pylori associated, active duodenal ulceration. All patients received pantoprazole, 40 mg b.d. for 2 weeks. Patients were randomized to receive either 1 or 2 weeks of therapy with amoxycillin, 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry, at 14 days and a minimum of 4 weeks after cessation of all therapy. H. pylori status was determined by urease reaction, histological assessment and culture from antral and body biopsies. Antibiotic sensitivity was determined using the agar dilution technique.

Results:

Sixty-seven patients were randomized. One week co-therapy (n = 33): eradication efficacy, ITT = 79% (95% CI: 61–91%); ulcer healing efficacy (at 6-week visit) = 88% (95% CI: 72–97%). Two-week co-therapy (n = 34): eradication efficacy, ITT = 91% (95% CI: 76–98%; ulcer healing efficacy = 88% (95% CI: 73–97%). Both regimens were well tolerated and no primary antibiotic resistance was noted.

Conclusion:

Pantoprazole-based triple therapy, with either 1 or 2 weeks of co-therapy with amoxycillin and clarithromycin, is effective in eradicating H. pylori and healing duodenal ulceration.

     

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.

     

Omeprazole, azithromycin and either amoxycillin or metronidazole in eradication of Helicobacter pylori in duodenal ulcer patients

Background

Azithromycin is a new generation, acid stable, macrolide antibiotic that achieves remarkably high concentrations in gastric tissue (above the minimal inhibitory concentration for Helicobacter pylori) after oral administration.

Aim

To establish whether azithromycin plus omeprazole in association with either amoxycillin or metronidazole are useful in curing H. pylori infection in patients with a duodenal ulcer.

Methods

One hundred patients with active duodenal ulcers and H. pylori infection were treated with omeprazole (days 1–10, 40 mg b.d.; days 11–24, 40 mg o.m.; days 25–42, 20 mg o.m.) plus azithromycin 500 mg o.m. for the first 6 days. Patients were randomly assigned to receive either amoxycillin 1 g b.d. (OAzA group; n = 50) or metronidazole 400 mg t.d.s. (OAzM group; n = 50) during the first 10 days of treatment. H. pylori status was determined by urease test and histology before the treatment and 6 weeks after completion of therapy.

Results

Ninety-seven patients completed the study. H. pylori infection was eradicated in 85% (41/48) of patients in the OAzA group (intention-to-treat analysis 82%) vs. 74% (36/49) of patients in the OAzM group (intention-to-treat analysis: 72%) (N.S.). All ulcers had healed after 6 weeks of omeprazole treatment. Side-effects, usually minor, were recorded in 13% (OAzA group) and 47% (OAzM group) of patients (P < 0.001), but therapy was discontinued for only one patient in the OAzA group (N.S.).

Conclusion

Ten days of treatment with omeprazole plus (for the first 6 days) azithromycin and either amoxycillin or metronidazole provides effective regimens to cure H. pylori infection in patients with duodenal ulcer disease.

     

Randomized comparison of 1-hour topical method vs. amoxycillin plus omeprazole for eradication of Helicobacter pylori in duodenal ulcer patients

Background:

A novel 1-h topical method eradicated Helicobacter pylori in 96% of dyspeptic patients. The eradication rate of amoxycillin/omeprazole therapy varies from 0 to 93%.

Aim:

To compare both methods in patients with endoscopically proven duodenal ulcer.

Methods:

Eighty patients (59 males, 21 females; median age 43 years) were randomized into two therapeutic groups. The first group (group A) was treated with a 6-week course of ranitidine 300 mg/day, then omeprazole 20 mg b.d. with pronase 36 000 units/day for 2 days, followed by 1-h topical therapy with a solution of bismuth, metronidazole, amoxycillin and pronase. The second group (group B) consisted of patients treated with omeprazole 20 mg b.d. and amoxycillin 2 g/day for 2 weeks, followed by a 4-week course of ranitidine 300 mg/day. Eradication of H.?pylori was assessed by urease test, histology, a polymerase chain reaction and a ¹³C-urea breath test, all of which were performed 4 weeks after discontinuation of the antibacterial treatment.

Results:

Eradication rates in groups A and B were 2.5% and 35% in an intention-to-treat analysis, respectively. Side-effects were encountered in 40.5% and 12.5% of subjects in groups A and B, respectively. Treatment tolerance was rated as poor by 54% of patients in group A and 2.5% of patients in group B.

Conclusions:

Both treatment regimens, the 1-h topical method and amoxycillin with omeprazole, have low eradication rates in patients with duodenal ulcer. In addition, the topical treatment is characterized by a high rate of side-effects and poor tolerance. Based on the results of our study, neither method can be recommended for eradication of H. pylori in patients with duodenal ulcer.

     

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.

     

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.

     

Low rate of emergence of clarithromycin-resistant Helicobacter pylori with amoxycillin co-therapy

Background:

Patients with persistent Helicobacter pylori infection following treatment with clarithromycin or omeprazole plus clarithromycin often develop clarithromycin resistance.

Aim:

To assess pre- and post-treatment antibiotic resistance in three double-blind trials of triple therapy with omeprazole, amoxycillin and clarithromycin.

Methods:

Patients with H. pylori and duodenal ulcer (studies 1 and 2) or history of duodenal ulcer (study 3) were randomly assigned to 10 day courses of omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) or placebo, amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (AC). Endoscopy was performed at baseline and 4 weeks after completion of therapy in studies 1 and 2, and at 4–6 weeks after therapy in study 3. At baseline, H. pylori was diagnosed by CLO test with confirmation by histology, or by culture. Eradication was defined as no positive biopsy test and ≥ 2 negative tests. Susceptibility testing was performed using the Etest.

Results:

In the 91 patients with pre-treatment susceptible isolates who had persistent infection after AC, 10 developed resistance, eight had intermediate susceptibility and 73 continued to have clarithromycin-susceptible H. pylori isolates. In the 10 patients with pre-treatment susceptible isolates who had persistent infection after OAC, three developed clarithromycin resistance and seven still had susceptible isolates.

Conclusions:

Use of amoxycillin co-therapy results in a low rate of clarithromycin resistance developing in patients with persistent H. pylori infection following therapy with a clarithromycin-containing regimen.

     

Ranitidine bismuth citrate versus omeprazole triple therapy for the eradication of Helicobacter pylori and healing of duodenal ulcer

Aim:

To compare the efficacy and safety of triple therapy with omeprazole plus amoxycillin and clarithromycin vs. ranitidine bismuth citrate plus amoxycillin and clarithromycin in the treatment of Helicobacter pylori-associated duodenal ulcers.

Methods:

Eighty-one patients with duodenal ulcers were randomized to the following treatments: 39 cases with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week plus omeprazole 20 mg b.d. for 2 weeks (omeprazole + amoxycillin + clarithromycin (OAC)), and 42 cases to the same regimen of amoxycillin and clarithromycin for 7 days plus ranitidine bismuth citrate 400 mg b.d. for 2 weeks (ranitidine bismuth citrate + amoxycillin + clarithromycin (RbAC)). Upper gastrointestinal endoscopy was performed together with a rapid urease test and histological examination of antral and corpus biopsy samples prior to treatment and 4 weeks after the end of therapy.

Results:

Thirty-four patients in the OAC group and 38 in the RbAC group completed the treatment and 4-week follow-up. H. pylori was eradicated in 30 of 34 patients (88%) in the OAC group and in 32 of 38 patients (84%) in the RbAC group according to a per-protocol analysis (P = N.S.). Thirty-three (97%) patients treated with OAC and 36 (95%) treated with RbAC presented healed duodenal ulcers at 4 weeks (P = N.S.). On an intention-to-treat basis there was no difference in H. pylori eradication between the OAC (77%) and RbAC groups (76%); duodenal ulcer healing was achieved in 85 and 86% of patients in the OAC and RbAC groups, re- spectively (P = N.S.).

Conclusion:

The OAC and RbAC triple therapy regimens proved equally effective in both H. pylori eradication and in duodenal ulcer healing.

     

Omeprazole and sucralfate in the treatment of NSAID-induced gastric and duodenal ulcer

Aim:

To establish the healing efficacy of two drugs, omeprazole and sucralfate, when given to patients who had developed gastric or duodenal ulcer while undergoing chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs).

Methods:

Ninety-eight patients with arthritis or arthrosis and NSAID-related gastric or duodenal ulcer were admitted to the endoscopic, single-blind study. They were randomized to receive either omeprazole 20 mg o.m. or sucralfate 2 g b.d. for 4–8 weeks. The patients continued to receive the same NSAID during the trial. Upper gastrointestinal endoscopy was performed at entry and after 4 or 8 weeks.

Results:

Eighty-eight patients completed the 4-week study, but only 81 were available for final analysis at 8 weeks. Omeprazole was significantly superior to sucralfate in inducing gastric ulcer healing after both 4 (87 vs. 52%, P = 0.007) and 8 weeks (100 vs. 82%, P = 0.04). No statistically significant difference in duodenal ulcer healing rates emerged between the two groups either at 4 (79 vs. 55%) or 8 weeks (95 vs. 73%). The healing rates in patients with combined gastric and duodenal ulcer were 67 vs. 33% after 4 weeks and 67 vs. 67% after 8 weeks of treatment. The percentages of asymptomatic patients were similar in the two treatment groups both at 4 (70 vs. 73%) and 8 weeks (70 vs. 75%). H. pylori infection did not influence healing rates, but significantly more H. pylori-positive patients healed with omeprazole.

Conclusions:

The results of this study show that omeprazole is superior to sucralfate in healing NSAID-induced gastroduodenal ulcer in patients who continue to take anti-inflammatory drugs. The good results observed were unrelated to H. pylori status.

     

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.

     

Helicobacter pylori-positive peptic ulcer patients do not adapt to aspirin

Background:

Recent studies indicate that eradication of Helicobacter pylori might prevent peptic ulcer formation in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). On the other hand, gastric adaptation after repeated exposures to aspirin (ASA) is well documented but the influence of H. pylori on this process remains to be elucidated.

Aim:

To compare gastric damage and adaptation following repeated exposures to ASA in a group of patients with H. pylori infection, before and after eradication of the bacterium, and in H. pylori-negative controls.

Methods:

Eight healthy volunteers without H. pylori infection and eight patients with duodenal ulcer (DU) history and H. pylori infection before and after H. pylori eradication were given ASA 2 g/day for a period of 14 days. Mucosal damage was evaluated by endoscopy and histology of biopsy samples. Gastric microbleeding, DNA synthesis in the gastric mucosa and mucosal expression, as well as luminal content of transforming growth factor-α (TGFα) were determined on days 0, 3, 7 and 14 of the ASA course.

Results:

In all patients aspirin-induced gastric damage reached a maximum on day 3. In H. pylori-positive patients, this damage was maintained at a similar level up to day 14, whereas in H. pylori-negative controls and H. pylori-eradicated patients this damage significantly lessened on day 14 and was accompanied by elevated DNA synthesis as well as increased mucosal expression and luminal release of TGFα.

Conclusions:

H. pylori-positive DU patients do not adapt to continued administration of ASA but eradication of the bacterium restores adaptation. This phenomenon deserves further clinical evaluation.

     

Lansoprazole triple therapy for Helicobacter pylori—is 5 days enough?

Background:

Seven-day proton pump inhibitor triple therapy is currently the treatment of choice for Helicobacter pylori infection. It is unclear whether triple therapy for less than 7 days might preserve efficacy while at the same time improving patient acceptability and compliance.

Aim:

To evaluate the Helicobactericidal efficacy, ulcer healing capacity and patient acceptability of a 5-day lansoprazole-based triple therapy regimen.

Methods:

Sixty-nine consecutive patients with H. pylori-positive peptic ulcer received lansoprazole 30 mg twice daily in combination with metronidazole 400 mg twice daily and clarithromycin 250 mg twice daily for 5 days. Ulcer healing medication was not continued after the 5-day regimen. H. pylori status was assessed before and at least 4 weeks after therapy by rapid urease test and histology. Adverse events and compliance were assessed by direct questioning.

Results:

All 69 patients attended for repeat endoscopy and 63 were H. pylori-negative after therapy giving a cure rate of 91% (95% Cl: 85–98%). Of the 59 patients with active ulcers, 58 were healed at repeat endoscopy giving an ulcer healing rate of 98% (95% Cl: 92–100%). All patients fully complied with therapy and mild adverse events, mainly gastrointestinal, were reported by 11 patients (16%).

Conclusions:

Five-day lansoprazole triple therapy is an effective regimen for H. pylori infection which combines a high cure rate and ulcer healing efficacy with the advantages of excellent patient acceptability and compliance.

     

Pantoprazole-based 10-day triple therapy is effective in Helicobacter pylori eradication

Aim:

To investigate the efficacy of a short course of pantoprazole-based triple therapy in Helicobater pylori eradication in a single-centre pilot study.

Methods:

Patients with active or healed duodenal ulcer or with gastric erosions or gastritis, all of whom were H. pylori-positive, received 10 days of twice-daily open treatment with pantoprazole 40 mg, plus clarithromycin 250 mg and tinidazole 500 mg. H. pylori was assessed at entry and 28–35 days after the end of treatment by rapid urease test (at entry only), culture and antimicrobial sensitivity, histology and ¹³ C urea breath test. The criterion for eradication was a negative result in all three tests.

Results:

Seventy patients were treated, of whom four were excluded from analysis due to major deviations from the study protocol. Eradication of H. pylori was achieved in 57/66 patients (per protocol analysis 86% (95% CI: 78–95%)) and was higher in patients with organisms sensitive to nitroimidazole before treatment (sensitive: 47/53 (89%), insensitive: 10/13 (77%)). There was marked reduction in acute gastritis throughout the stomach while chronic gastritis decreased only in the corpus. Healing was achieved in all 24 patients with active duodenal ulcer. Treatment was complied with; only one patient missed one of the 20 doses. Adverse events were of mild or moderate intensity and did not require withdrawal from treatment.

Conclusion:

A short course of pantoprazole-based triple therapy is well tolerated and effective in eradicating H. pylori.

     

Eradication of Helicobacter pylori with lansoprazole, roxithromycin and metronidazole—an open pilot study

Background:

The most extensively studied Helicobacter pylori eradication regimen comprises omeprazole, clarithromycin and metronidazole. Macrolide antibiotics other than clarithromycin should achieve similar efficacy, but they have not yet been thoroughly tested.

Aim:

To determine the efficacy and safety of a triple therapy regimen using lansoprazole, roxithromycin, and metronidazole on the basis of multicentre out-patient care in an open pilot study.

Methods:

163 patients with duodenal ulcer and proven H. pylori infection received lansoprazole 30 mg b.d., roxithromycin 300 mg b.d. and metronidazole 500 mg b.d. for 7 days followed by another 7 days of lansoprazole 30 mg once daily. H. pylori status was determined by urease quick test, histology, microbiology and ¹³C-urea breath test before starting and at least 4 weeks after completing treatment.

Results:

150 patients were available for evaluation; H. pylori was successfully eradicated in 84.7% (127/150) as determined by urease quick test, 78.0% (117/150) by histology, 81.3% (109/134) by ¹³C-urea breath test; and in 75.3% (113/150), at least two tests were negative. Side-effects were reported in 34 patients (most commonly diarrhoea and changes in liver function tests), in two cases the study medication was interrupted. Prior to treatment, 23% of the H. pylori isolates were resistant against metronidazole and 3.4% against roxithromycin. After unsuccessful treatment, 84% of the isolates were resistant against metronidazole and 21% against roxithromycin. Primary resistance to metronidazole increased the chance of treatment failure approximately sevenfold (7% vs. 53%).

Conclusions:

For H. pylori eradication, the combination of lansoprazole, roxithromycin and metronidazole proved to be as safe as other current triple therapy regimens, while a comparison of efficacy rates yet remains to be assessed in prospective controlled trials. The metronidazole-resistant H. pylori is not rare in Germany and, in the present study, has strongly influenced treatment success.

     

US double-blind, controlled trials of omeprazole and amoxycillin for treatment of Helicobacter pylori

Background:

Widely variable Helicobacter pylori eradication rates have been reported with omeprazole/amoxycillin dual therapy. We present the first US double-blind, controlled trials of this dual therapy.

Methods:

Three separate studies were performed: Studies 1 and 2 included patients with an active duodenal ulcer and Study 3 included patients with a documented history of duodenal ulcer. H. pylori eradication regimens in all studies were omeprazole plus amoxycillin vs. omeprazole vs. amoxycillin for 2 weeks. Doses in Study 1 were omeprazole 40 mg b.d. and amoxycillin 500 mg t.d.s., and in Studies 2 and 3 they were omeprazole 20 mg b.d. and amoxycillin 1 g t.d.s. Endoscopic biopsy tests were used for H. pylori diagnosis, and testing for H. pylori eradication was done at least 4 weeks after the completion of therapy. Amoxycillin sensitivities were performed in Study 2.

Results:

Intention-to-treat (ITT) and per protocol (PP) analyses showed that eradication rates with omeprazole/amoxycillin [ITT: 39%, 40%, 46% (n = 72, 62, 48); PP: 50%, 46%, 54% (n = 54, 52, 37)] were significantly greater than monotherapy with either omeprazole (ITT: 0–4%; PP: 0–5%) or amoxycillin (ITT: 2–5%; PP: 0–11%). No patients taking the dual therapy discontinued therapy due to adverse events. Amoxycillin resistance was not seen at baseline (n = 76) or after amoxycillin therapy (n = 56).

Conclusions:

Omeprazole/amoxycillin dual therapy is well tolerated but the eradication rate which can be expected in the USA is at best about 50%.