|A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection
|Calvet X, Garcia N, Lopez T, Gisbert J P, Gene E, Roque M
To evaluate whether increasing the length of triple therapies beyond seven days improves efficacy in the treatment of Helicobacter pylori infection.
The authors searched MEDLINE from 1990 to March 1999 using the following strategy: 'Helicobacter pylori' (all fields), and each of the following terms: '7', 'seven', 'week', 'weeks', '10', 'ten', '12', 'twelve', '14', 'fourteen', 'clarithromycin', 'amoxycillin', 'omeprazole', 'lansoprazole', 'pantoprazole', 'proton pump inhibitor' and 'triple' (titles). Additional material was obtained by examining references of retrieved articles and reviews on H. pylori treatment, and by manually searching abstracts submitted to the American Gastroenterological Association congresses (1995 to 1998) and the European Helicobacter pylori Study Group congresses on H. pylori treatment (1996 to 1998).
Study designs of evaluations included in the review
Randomised controlled trials (RCTs) comparing short (7-day) versus long (10- to 14-day) therapies, and three-way comparisons of 7- versus 10-day, 10- versus 14-day, and 7- versus 14-day therapies.
Specific interventions included in the review
Short (7-day) versus long (10- to 14-day) triple therapy using a combination of proton pump inhibitor (PPI), clarithromycin, and either metronidazole, amoxycillin or a nitroimidazole, all administered twice daily.
Participants included in the review
Patients undergoing treatment for H. pylori infection, as diagnosed using 2 different diagnostic tests.
Outcomes assessed in the review
Eradication of H. pylori determined by histology or 13C-urea breath test. Side-effects of therapy.
How were decisions on the relevance of primary studies made?
The authors do not state how the papers were selected for the review, or how many of the reviewers performed the selection.
Assessment of study quality
No formal assessment of quality was undertaken.
The authors do not state how the data were extracted for the review, or how many of the reviewers performed the data extraction.
Data were extracted for the categories: author, format, year, design, diagnosis of patients, treatment, length of treatment, side-effects, and intention to treat (ITT) analysis.
Methods of synthesis
How were the studies combined?
Pooled odds ratios (ORs) were calculated with 95% confidence intervals (CIs) using a fixed-effect model. Calculations were performed on both an ITT and a per protocol basis. Number-needed-to-treat (NNT) was also calculated.
How were differences between studies investigated?
The chi-squared test was used to assess heterogeneity.
Results of the review
Thirteen RCTs were included in the review; only those with ITT analysis were included. Seven RCTs compared 14- versus 7-day therapies (339 versus 470 participants), 3 RCTs compared 14- versus 10-day therapies, and 2 RCTs compared 7- versus 10-day therapies.
Pooled 14-day therapies (7 studies) achieved better results than 7- day schedules (OR 0.62, 95% CI: 0.45, 0.84), heterogeneity 4.13 (d.f.=6, Z=3.03). In head-to-head comparisons, only 14-day therapies were significantly better than 7-day treatments. Improvement in cure rates ranged from 7 to 9%. The NNT ranged from 6 to 23 patients.
Comparisons of 7- versus 10-day and 10- versus 14-day also showed a non significant trend towards better cure rates with longer therapies.
Pooled 14-day therapies (3 studies) were not statistically- significantly better than 10-day schedules (OR 0.88, 95% CI: 0.54, 1.43), heterogeneity 0.30 (d.f.=2, Z=0.51).
Pooled 10-day therapies compared to 7-day schedules cannot be determined, since the results (graph) for this pooling is a duplicate of the 14- versus 10-day figure.
The authors state that side-effects tended to be more frequent in longer therapies, although the difference was not statistically significant in any of the comparisons. The authors do not present any information in paper to enable this statement to be assessed.
The authors state that 14-day, PPI-based triple therapy achieves better results than 7-day schedules. Additional data are necessary to evaluate 10-day therapies.
The authors have stated the research question, and inclusion and exclusion criteria. The literature search was limited by searching MEDLINE only, and it is unclear whether the search was restricted to English language publications. It is possible that additional relevant studies may have been missed.
The quality of the included studies was not formally assessed, although the authors limited the included studies to RCTs. The authors have also not reported how the articles were selected, or who performed the selection and data extraction.
The data extraction is reported in a table and discussed in the text of the review. The studies were combined in a statistical meta-analysis and heterogeneity was assessed. No significant heterogeneity between the studies was found. No information on side-effects was reported in the paper to support the authors' statements, so these results are not verifiable.
The authors' conclusions appear to follow from the results, but should be viewed with caution because of limitations in the quality of the review process.
Implications of the review for practice and research
Practice: The authors state that 14-day triple therapies are costly, uncomfortable for patients and carry an increased risk of side-effects. In addition, their ability to overcome clarithromycin resistance has not been established. Thus, conditions other than eradication rates should be taken into account when choosing between 7- and 10- or 14-day therapies.
Research: The authors state that further larger studies are needed comparing both 7- and 10-day schedules and 10- to 14-day therapies. The studies should evaluate not only the efficacy, but also the cost-effectiveness of different lengths of therapy. Differences in antibiotic resistance and heterogeneity caused by genetic differences in H. pylori, which might affect a population's susceptibility, also need to be considered.
Calvet X, Garcia N, Lopez T, Gisbert J P, Gene E, Roque M. A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Alimentary Pharmacology and Therapeutics 2000; 14(5): 603-609
Subject indexing assigned by NLM
Amoxicillin /administration & Anti-Bacterial Agents /administration & Anti-Ulcer Agents /administration & Clarithromycin /administration & Drug Administration Schedule; Drug Therapy, Combination; Helicobacter Infections /drug therapy /pathology; Helicobacter pylori /drug effects; Humans; Metronidazole /administration & Proton Pump Inhibitors; Treatment Outcome; dosage /therapeutic use; dosage /therapeutic use; dosage /therapeutic use; dosage /therapeutic use; dosage /therapeutic use
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.