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Pharmacological therapy of Helicobacter pylori infection
Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
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.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 734
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-26674Local ID: 11241ISBN: 91-7373-178-1 (print)OAI: oai:DiVA.org:liu-26674DiVA: diva2:247223
Public defence
2002-05-24, B-husets aula, Örebro Universitetssjukhus, Örebro, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-13Bibliographically approved
List of papers
1. Does Omeprazole Improve Antimicrobial Therapy Directed Towards Gastric Campylobacter Pylori in Patients with Antral Gastritis?: A Pilot Study
Open this publication in new window or tab >>Does Omeprazole Improve Antimicrobial Therapy Directed Towards Gastric Campylobacter Pylori in Patients with Antral Gastritis?: A Pilot Study
1989 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 24, no s167, 49-54 p.Article in journal (Refereed) Published
Abstract [en]

This double-blind pilot study has been undertaken in order to investigate the effect of amoxicillin and pronounced suppression of gastric acid secretion on mucosal colonisation with Campylobacter pylori (CP). Twentyfour CP-positive patients were included in the study and assigned to 14 days of treatment in either one of the following three therapy groups: Group 1: Omeprazole 40 mgo.m. + Amoxicillin 750 mgb.i.d (9pat); Group 2: Omeprazole 40 mg o.m. (8 pat); Group 3: Amoxicillin 750 mg b.i.d (7 pat).Gastroscopy with biopsy for culture and histology was performed pre-entry, at cessation of therapy and four weeks later. In the group receiving omeprazole and amoxicillin in combination 5 out of 8 patients were negative for CP four weeks after stopping treatment, while in the amoxicillin and the omeprazole groups respectively one (1/7) and none (0/8) were negative. Except for one patient who was withdrawn because of severe diarrhoea, only minor adverse effects occurred.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81384 (URN)10.3109/00365528909091311 (DOI)
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
2. Amoxicillin added to omeprazole prevents relapse in the treatment of duodenal ulcer patients
Open this publication in new window or tab >>Amoxicillin added to omeprazole prevents relapse in the treatment of duodenal ulcer patients
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1993 (English)In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 5, no 5, 325-332 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To evaluate two different therapies, omeprazole/amoxicillin versus omepra-zole alone, in the treatment of duodenal ulcer patients with respect to eradication of Helicobacter pylori and time in remission during a 6-month follow-up after cessation of therapy.

Design: Double-blind, randomized, parallel groups.

Setting: Outpatient referrals in nine Swedish centres.

Patients: This study included 248 patients with active duodenal ulcer.

Main outcome measures: Endoscopic and symptomatic evaluation of time in remission. Culture, histology and serology for determination of H. pylori status.

Results: Eradication of H. pylori was 54 compared with 4% and the proportion of patients in remission at 6 months was 70 compared with 36% in the omeprazole/amoxicillin treated group versus the group treated with omeprazole alone. Of the patients who became H. pylori-negative, 84% were in remission throughout the study.

Conclusion: H. pylori is an almost obligate prerequisite for duodenal ulcer disease. Amoxicillin added to omeprazole nearly doubled the proportion of patients in remission at 6 months follow-up. The eradication rate of H. pylori in patients with excellent compliance was 74%.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81385 (URN)
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
3. Eradication of Helicobacter pylori Using One-week Triple Therapies Combining Omeprazole with Two Antimicrobials: The MACH I Study
Open this publication in new window or tab >>Eradication of Helicobacter pylori Using One-week Triple Therapies Combining Omeprazole with Two Antimicrobials: The MACH I Study
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1996 (English)In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 1, no 3, 138-144 p.Article in journal (Refereed) Published
Abstract [en]

Background.Eradication of Helicobacter pylori provides potential cure in the majority of patients with peptic ulcer disease, and eradication rates of more than 90% have been reported, using omeprazole in combination with two antimicrobials. The choice of antimicrobials, dose regimen and duration of treatment have varied between studies, however, and an optimal treatment still has to be established.

Materials and Methods.We conducted an international, randomized, double-blind, placebo-controlled study involving more than 100 patients in each of six treatment groups in 43 hospital gastrointestinal units in Canada, Germany, Ireland, Sweden, and the United Kingdom. Patients (n=787) with proved duodenal ulcer disease were randomized to treatment twice daily for 1 week with omeprazole, 20 mg (O), plus either placebo (P) or combinations of two of the following anti-microbials: amoxicillin, 1 gm (A), clarithromycin, 250 or 500 mg (C250, C500), or metronidazole, 400 mg (M). Eradication of H. pylori was evaluated by 13C-UBT, performed before and 4 weeks after treatment cessation.

Results.The eradication rates for the all-patients-treated analysis were 96%. OAC500; 95%, OMC250; 90%, OMC500; 84%, OAC250; 79%, OAM; and 1%, OP. OAC500 and OMC250 achieved eradication rates with lower 95% confidence interval limits exceeding 90%. All regimens were well-tolerated, 96% of patients complied with their dose regimen, and 2.3% of the patients discontinued treatment owing to adverse events.

Conclusions.Omeprazole triple therapies given twice daily for 1 week produce high eradication rates, are well-tolerated, and are associated with high patient compliance. The two most effective therapies were those combining omeprazole, 20 mg, with either amoxicillin, 1 gm, plus clarithromycin, 500 mg, or metronidazole, 400 mg, plus clarithromycin, 250 mg, all given twice daily.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81386 (URN)10.1111/j.1523-5378.1996.tb00027.x (DOI)
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
4. The MACH2 study: Role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies
Open this publication in new window or tab >>The MACH2 study: Role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies
Show others...
1999 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, 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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81387 (URN)10.1016/S0016-5085(99)70119-8 (DOI)
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
5. The Cost Effectiveness of Helicobacter pylori Eradication versus Maintenance and Episodic Treatment in Duodenal Ulcer Patients in Sweden
Open this publication in new window or tab >>The Cost Effectiveness of Helicobacter pylori Eradication versus Maintenance and Episodic Treatment in Duodenal Ulcer Patients in Sweden
1995 (English)In: PharmacoEconomics (Auckland), ISSN 1170-7690, E-ISSN 1179-2027, Vol. 8, no 5, 410-427 p.Article in journal (Refereed) Published
Abstract [en]

This study compares the cost effectiveness of Helicobacter pylori eradication and conventional treatment in duodenal ulcer patients treated by a general practitioner. Using a Markov chain approach, Swedish cost data and a study period of 5 years, we conclude that H. pylori eradication with omeprazole and appropriate antibiotics is a cost-effective alternative compared with both maintenance and episodic treatment. Of the patients entering the eradication strategy, most are cured and will have no relapse during a 5-year period. H. pylori eradication results in higher initial costs but, because of a very low risk of recurrence after successful eradication, the expected future costs are reduced. The investment pays off within 1 year when compared with maintenance treatment, and within 3 years when compared with episodic treatment.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81388 (URN)10160075 (PubMedID)
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved

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