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The MACH2 study: Role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies
Department of Surgery, Kärnsjukhuset, Skövde, Sweden.
Laboratoire de Bactériologie, Hôpital Pellegrin, Bordeaux, France.
Department of Internal Medicine, Sandvikens Hospital, Sandviken, Sweden.
Medizinische Klinik I–Gastroenterologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany.
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1999 (English)In: Gastroenterology, ISSN 0016-5085, Vol. 116, no 2, 248-253 p.Article in journal (Refereed) Published
Abstract [en]

Background & Aims: The role of omeprazole in triple therapy and the impact of Helicobacter pylori resistance on treatment outcome are not established. This study investigated the role of omeprazole and influence of primary H. pylori resistance on eradication and development of secondary resistance.

Methods: Patients (n = 539) with a history of duodenal ulcer and a positive H. pylori screening test result were randomized into 4 groups. OAC group received 20 mg omeprazole, 1000 mg amoxicillin, and 500 mg clarithromycin; OMC group received 20 mg omeprazole, 400 mg metronidazole, and 250 mg clarithromycin; and AC (amoxicillin, 1000 mg, and clarithromycin, 500 mg) and MC (metronidazole, 400 mg, and clarithromycin, 250 mg) groups received no omeprazole. All doses were administered twice daily for 1 week. H. pylori status was assessed before and after therapy by 13C-urea breath test. Susceptibility testing was performed at entry and in patients with persistent infection after therapy.

Results: Eradication (intention to treat [n = 514]/per protocol [n = 449]) was 94%/95% for OAC, 26%/25% for AC (P < 0.001), 87%/91% for OMC, and 69%/72% for MC (P < 0.001). Primary resistance was 27% for metronidazole, 3% for clarithromycin, and 0% for amoxicillin. Eradication in primary metronidazole-susceptible/-resistant strains was 95%/76% for OMC and 86%/43% for MC. Secondary metronidazole and clarithromycin resistance each developed in 12 patients: 8 treated with omeprazole and 16 without omeprazole.

Conclusions: Addition of omeprazole achieves high eradication rates, reduces the impact of primary resistance, and may decrease the risk of secondary resistance compared with regimens containing only two antibiotics.

Place, publisher, year, edition, pages
1999. Vol. 116, no 2, 248-253 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-81387DOI: 10.1016/S0016-5085(99)70119-8OAI: diva2:552148
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2012-09-13Bibliographically approved
In thesis
1. Pharmacological therapy of Helicobacter pylori infection
Open this publication in new window or tab >>Pharmacological therapy of Helicobacter pylori infection
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The discovery of Helicobacter pylori (H. pylori) opened the doors to new insight and therapy for peptic ulcer disease. Earlier eradication treatment modalities based on bismuth compounds, with or without additional antimicrobials, were not well accepted mainly because of the, at least hypothetical, risks for neurological and/or renal side effects. The first proton pump inhibitor, omeprazole, had been proven as a very effective short-term anti-ulcer therapy, but after withdrawal of the drug, the recurrence rate was high. theoretically, acid suppression was believed to increase the H. pylori infestation as the environment became more neutral. On the other hand, acid suppression could increase the effect of acid labile antimicrobials. This was not investigated before the studies presented in this thesis were performed.

A small pilot study (Paper I) in 24 patients showed that 7 out of 8 patients treated for fourteen days with omeprazole 40 mg o.m. + amoxicillin 750 mg b.i.d. were cleared of H. pylori, while it remained in 7/8 patients on omeprazole as monotherapy and in 2/7 patients on amoxicillin as monotherapy. However, the eradication rates 4 weeks after treatment were 5/8, 0/8 and 1/7 in the three groups, respectively. These results were confirmed in a large study (Paper II) comprising 248 consecutive patients with active duodenal ulcer disease. All had an initial treatment period for two weeks with omeprazole 40 mg o.m., followed by continued omeprazole in combination with amoxicillin 750 mg b.i.d. or amoxicillin placebo for a further two weeks. In the dual therapy group, 54% of patients were H. pylori eradicated compared to 4% in the omeprazole mono therapy group. Furthermore, the duodenal ulcer relapse rate was significantly lower in the combination group compared to the monotherapy group (p<0,001). Paper III represents a study that was preformed to assess whether improved results could be obtained by adding two antimicrobials to omeprazole. In total 787 patients were randomized to six treatment arms, where omeprazole was combined with two of the three antimicrobials amoxicillin, metronidazole and c!arithromycin in various doses and combinations. The results showed that one week's treatment was sufficient for a very high eradication rate. A combination of omeprazole 20 mg b.i.d. + amoxicillin 1000 mg b.i.d. + clarithromycin 500 mg b.i.d. was superior to a combination with a lower clarithromycin dose of 250 mg b.i.d. or amoxicillin in combination with metronidazole, but not significantly better than the other two arms containing metronidazole+ clarithromycin in a dose of 250 mg b.i.d. 500 mg b.i.d. Paper IV was designed to establish whether or not acid suppression is necessary during antimicrobial treatment. In total 539 patients were randomized. Eradication rates with omeprazole added to antimicrobials were much higher than in treatment groups not receiving omeprazole. In metronidazole resistant strains, only 76% were eradicated in comparison to 95% in susceptible strains. Amoxicillin resistance did not occur and clarithromycin resistance was found in only 3% of patients. Thus, papers I-IV proved the efficacy ofthe new treatment modality, which, however, represented high costs in the short-term perspective.

The cost-effectiveness of various treatment strategies in regular use at that time was evaluated in paper V. The economic model showed that in comparison to continuous therapy with gastric acid suppressive drugs, the extra initial cost for eradication therapy was paid within one year and, in comparison to intermittent therapy, within three years.

Conclusion: These studied have shown convincingly that eradication of H. pylori with a combination of gastric acid suppression and two antimicrobials (amoxicillin and clarithromycin) is the most effective treatment in PUD, giving a high eradication rate and consequently lower peptic ulcer recurrence. Thus, this treatment strategy is also very cost-effective for society.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2002. 67 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 734
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-26674 (URN)11241 (Local ID)91-7373-178-1 (ISBN)11241 (Archive number)11241 (OAI)
Public defence
2002-05-24, B-husets aula, Örebro Universitetssjukhus, Örebro, 13:00 (Swedish)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-13Bibliographically approved

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