A single drug for Helicobacter pylori infection: first results with a new bismuth triple monocapsule.

OBJECTIVE: In this pilot study we investigated the efficacy and tolerability of a new monocapsule that contains a bismuth compound, tetracycline, and metronidazole. If proven to be effective, this monotherapy would turn the well-accepted multidrug regimen of standard bismuth-based triple therapy into an easy and more patient-friendly regimen. It can be used in patients allergic to penicillin. METHODS: A total of 53 consecutive H. pylori-infected patients (30 with proven ulcer disease, 23 with gastritis only) from a single center were prescribed two monocapsules q.i.d. after the three meals and after an evening snack during 10 days. Each capsule contained 60 mg colloidal bismuth subcitrate (as Bi2O3 equivalent), 125 mg tetracycline, and 125 mg metronidazole. Repeat endoscopy with biopsies for urease test, Giemsa stain, and culture was carried out > or =5 wk later. Side effect data were collected. RESULTS: One patient was lost to follow-up, two failed to respond, and 50 were cured. The intention-to-treat cure rate was 50 of 53 (94.4%, 95% CI 88.1-100%). Antibiotic sensitivity was available from 51 isolates. The cure rate in the metronidazole sensitive strains was 44 of 45 (97.8%, 95% CI: 93.5-100%), whereas it was four of five in the resistant strains. The regimen was well tolerated, with only two drop-outs (4%) because of side effects. CONCLUSIONS: The new monocapsule is an inexpensive, well tolerated, and patient-friendly formulation of a bismuth based triple therapy. A 10-day course with this multidrug capsule reached a very high cure rate in metronidazole-sensitive strains. The number of cases with resistant strains was insufficient to allow firm conclusions about its efficacy in case of resistance. The results are in agreement with previous data with bismuth triple therapy using separate drugs. From the high cure rate, we can conclude that the new capsule dissolves adequately, with proper delivery of its ingredients at the site of action.

Bismuth-based quadruple therapy for Helicobacter pylori - a single triple capsule plus lansoprazole.

BACKGROUND: Recently a new 'all in one' single capsule with the three components of bismuth-based triple therapy became available in trials for treating Helicobacter pylori. AIM: To investigate the efficacy and tolerability of this new capsule when combined with lansoprazole. METHODS: A total of 66 consecutive infected patients from a single centre received two single triple capsules four times daily and lansoprazole 30 mg b.d. for 7 days. Each capsule contained 60 mg of bismuth subcitrate, 125 mg of tetracycline and 125 mg of metronidazole. Endoscopy with biopsies for CLO-test, histology and culture from antrum and corpus was performed before and at least 5 weeks after treatment. RESULTS: The per protocol cure rate was 56/64 (88%, 95% CI: 79-95%); by intention-to-treat 56/65 (86%, 95% CI: 78-95%). The per protocol cure rate in metronidazole sensitive strains was 40/43 (93%, 95% CI: 85-100%); in resistant strains 5/9 (56%, 95% CI: 23-88%). There was one drop-out due to adverse events. CONCLUSIONS: It is possible to combine the components of bismuth-based triple therapy into a single capsule. Based on the results it can be assumed that the capsule releases its content in the stomach. When combined with lansoprazole it reaches high cure rates, especially in metronidazole sensitive strains. This new approach simplifies bismuth-based anti-Helicobacter therapy.

Two-day 'weekend' lansoprazole-quadruple therapy for Helicobacter pylori infection.

BACKGROUND: The very high cure rate of 1-week quadruple therapy offers an opportunity to study a shorter treatment duration. This is needed to construct a time-response curve for the regimen. METHODS: Fifty-two patients with endoscopically proven H. pylori infection received lansoprazole 30 mg b.d., tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 500 mg q.d.s. and metronidazole 500 mg q.d.s., following 3 days of lansoprazole pre-treatment. A second endoscopy was performed at least 6 weeks later. A patient was cured if histology, CLO-test, and culture of antrum and corpus were negative. RESULTS: We achieved an intention-to-treat cure rate of 30/50 (60%, 95%, CI: 46-73%) and a per protocol cure rate of 30/48 (63%, 95% CI: 48-75%). Cure rate in metronidazole-sensitive strains was 24/37 (65%, 95% CI: 48-79%) and 2/5 (40%) in resistant strains. All patients that failed the regimen had a metronidazole-resistant strain post-treatment. Compliance was excellent and moderate or severe side-effects occurred in only 4% of patients. CONCLUSION: A 2-day 'weekend' quadruple therapy cures only 60% of patients and cannot be recommended, but these findings provide an insight into the mode of action of quadruple therapy.

Four-day lansoprazole-quadruple therapy in the routine treatment of Helicobacter pylori infection.

BACKGROUND: Ulcer patients need to be treated for Helicobacter pylori infection. Seven days of quadruple therapy achieves the highest cure rates. In this study a 4-day quadruple regimen of lansoprazole, bismuth, tetracycline and metronidazole is investigated. METHODS: In an open study 66 consecutive infected patients with ulcer disease or non-ulcer dyspepsia were treated with 4-day quadruple therapy after 3 days of lansoprazole pretreatment. H. pylori status was determined before and at least 6 weeks after therapy by endoscopy with antral and corpus biopsies for rapid urease test, histology and culture. RESULTS: Sixty-four patients took the medication and complete compliance was achieved in 60 (94%). Tolerability was excellent and there were no drop-outs due to side-effects. Overall 55 out of 64 (86%, 95% CI 77.4-94.4%) were cured, including 41/44 with a metronidazole-sensitive strain 5/8 with a resistant strain. CONCLUSIONS: Four-day quadruple therapy is well tolerated and very effective especially in metronidazole-sensitive strains. This study lends further support for the use of one-week quadruple therapy as empiric first line anti-Helicobacter therapy for Dutch ulcer patients. If patients suffer from side-effects during this therapy stopping treatment at day 4 can be advised.

One-day intensified lansoprazole-quadruple therapy for cure of Helicobacter pylori infection.

BACKGROUND: Peptic ulcer patients need to be treated with antimicrobials to cure Helicobacter pylori infection. Seven-day quadruple therapy is the regimen with the highest cure rates. An ultra-short quadruple therapy was evaluated prospectively. METHODS: Forty-six consecutive H. pylori positive patients (33 had proven ulcer disease) were prescribed lansoprazole 30 mg b.d. on days 1-4, and on day 4 they received in addition tripotassium dicitrato bismuthate 120 mg, tetracycline 250 mg and metronidazole 250 mg at 09.00, 11.00, 13.00, 15.00, 17.00, 19.00, 21.00, 23.00 hours. Repeat endoscopy with biopsies for CLOtest, Giemsa stain and culture was carried out 6 weeks later. RESULTS: Follow-up was complete. Overall cure rate (all three biopsy-based tests negative) was 26/46 (57%; 95% CI: 41-71%). Antibiotic sensitivity was available in 42. Thirty-nine carried a metronidazole sensitive strain and 23/39 (59%) were cured, three carried a resistant strain and therapy failed in all. Three out of four in whom susceptibility was unknown were cured. Metronidazole resistance was induced in 8 out of 16 with a sensitive strain. Only one patient (3%) reported severe side effects. CONCLUSIONS: This convenient quadruple regimen showed that a short contact time is sufficient to kill H. pylori in vivo. Since 57% of patients are cured with a 14-h treatment, a slightly longer treatment duration may increase the cure rate to above 90%.

4-day lansoprazole quadruple therapy: a highly effective cure for Helicobacter pylori infection.

OBJECTIVES: We have advocated quadruple therapy as the optimal therapy for cure of Helicobacter pylori infection. In this study, we investigated the efficacy and tolerability of 4-day therapy with lansoprazole, bismuth, tetracycline, and metronidazole. METHODS: In a prospective open study, 51 consecutive patients, most of them with chronic peptic ulcer disease and biopsy proven H. pylori infection, received 4-day lansoprazole quadruple therapy after 3 days of lansoprazole pretreatment. Repeat endoscopy was performed 6 wk later, with antral and corpus biopsies for rapid urease test, histology, and culture. A patient was considered cured if three methodologies had negative results. RESULTS: By intention-to-treat, 48 of 51 patients (94%) (95% CI 84%-99%) were cured; per protocol, 48 of 49 (98%) (95% CI 89%-100%) were cured. In 14 patients, the bacterial isolates were tested for metronidazole susceptibility: 12/12 with a sensitive strain were cured, as were 2/2 with a resistant strain. The regimen was well tolerated. Most side effects were mild, and none caused treatment to be stopped prematurely. CONCLUSIONS: Four-day lansoprazole quadruple therapy achieves a very high cure rate in an unselected population of mainly ulcer patients. Furthermore, the regimen is short, can be used in patients allergic to penicillin, and is well tolerated, with no dropouts due to side effects. Presently, this regimen should be used only in patients with a metronidazole-sensitive pre-treatment bacterial isolate. When empiric treatment is used, 7-day quadruple therapy remains the therapy of choice, because it has well-documented efficacy against metronidazole-resistant strains. Further studies are needed to define the optimal treatment duration for quadruple therapy in patients with metronidazole-resistant strains.

Effectiveness of quadruple therapy using lansoprazole, instead of omeprazole, in curing Helicobacter pylori infection.

BACKGROUND: Omeprazole enhances the efficacy of bismuth-based triple therapy. It is unknown whether the same is true for other proton pump inhibitors. Lansoprazole has superior anti-Helicobacter activity in vitro and possibly also in vivo; therefore we investigated quadruple therapy with lansoprazole. MATERIALS AND METHODS: In two studies performed in separate hospitals, a total of 67 Helicobacter pylori-positive patients were treated with 7-day quadruple therapy (lansoprazole, colloidal bismuth subcitrate, tetracycline, and metronidazole) after 3 days of lansoprazole pretreatment. Testing for cure was done by endoscopy in study 1 and by breath test in study 2. RESULTS: Cure rates per protocol were 31 of 31 (100%) in study 1 and 30 of 32 (94%) in study 2. Intention-to-treat cure rates were 31 of 35 (89%) in study 1 and 30 of 32 (94%) in study 2. Cured overall were 32 of 34 with a metronidazole sensitive strain and 3 of 3 with a metronidazole-resistant strain. Data on side effects were collected from 51 patients. Twelve (21%) had no side effects, 27 (53%) had mild side effects, 10 (20%) had moderate side effects, but only 2 (4%) had severe side effects. Side effects, never were the reason that a patient stopped taking the medication. CONCLUSIONS: The results with lansoprazole-quadruple therapy are comparable to the historic control group treated with omeprazole-quadruple therapy. The cure rare is very high, and although mild to moderate side effects occurred in many patients, everybody finished the treatment regime.