|Empiric quadruple vs triple therapy for primary treatment of Helicobacter pylori infection: systematic review and meta-analysis of efficacy and tolerability
|Luther J, Higgins PD, Schoenfeld PS, Moayyedi P, Vakil N, Chey WD
This review concluded that quadruple and triple therapy for the primary treatment of Helicobacter pylori infection resulted in similar, suboptimal eradication rates, and similar patient compliance and side effects. Although the authors’ conclusions appeared to reflect the evidence, given the limitations with the review and the heterogeneity among the included trials, they should be interpreted with some caution.
To compare the efficacy and tolerability of quadruple and triple therapy as first-line treatment of Helicobacter pylori infection.
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), DARE, Cochrane Methodology Register, HTA database and ACP Journal Club were searched for articles published after 1990. Search terms were reported. In addition, reference lists were manually searched, as were abstracts presented at Digestive Disease Week and the American College of Gastroenterology Annual Scientific Meeting (2003 to 2008) and Google Scholar.
Randomised controlled trials (RCTs) that compared bismuth quadruple therapy (metronidazole, bismuth-containing compound, tetracycline, and proton pump inhibitors) with clarithromycin triple therapy (amoxicillin, clarithromycin, and proton pump inhibitors) of the same duration in patients with Helicobacter pylori (H. pylori) were eligible for inclusion. Methods of H. pylori diagnosis had to include urea breath test, rapid urease test, histology, and/or faecal antigen testing.
Outcomes of interest were: intention-to-treat eradication rate; eradication tested with urea breath test and/or histology at least four weeks after therapy was complete; compliance rates; and the number of side effects.
Included trials were conducted in Australia/New Zealand, Greece, India, Korea, Spain, Turkey, UK and USA/Canada. Patients received varying treatment regimens lasting seven, 10 or 14 days. Some trials included only patients with evidence of peptic ulcer disease and other trials included only patients without peptic ulcer disease.
The authors did not state how many reviewers screened studies for inclusion.
Assessment of study quality
The authors did not state that they performed a validity assessment.
Two reviewers independently extracted the number of patients in whom eradication of H. pylori was a success or failure to calculate risk ratios (RRs) and their 95% confidence intervals (CIs). The number of patients reporting the presence or absence of side effects and compliance rates were also extracted. Discrepancies were resolved by consensus.
Methods of synthesis
A random-effects model was used to pool risk rates and 95% confidence intervals. Statistical heterogeneity was assessed using the I2 statistic, with I2 more than 70% indicating significant heterogeneity. Subgroup analyses were undertaken by location (Eastern versus Western Hemisphere), treatment duration (seven, 10, and 14 days), and patient type (ulcer versus non-ulcer dyspepsia). In addition, analyses were performed to assess changes in eradication rates over time (trials conducted in 2005 and after versus trials conducted before 2005).
Publication bias was assessed using funnel plots, Begg’s test, and Egger’s test.
Results of the review
Nine RCTs (n=1,679 patients) were included in the review. Sample sizes ranged from 68 to 339 patients.
There were no statistically significant differences in H. pylori eradication rates between patients receiving bismuth quadruple therapy and patients receiving clarithromycin triple therapy (RR 1.00, 95% CI 0.94 to 1.07). Intention-to-treat eradication rates were suboptimal for both therapies (less than 80%). There was evidence of moderate statistical heterogeneity (I2=43.9%).
Subgroup analyses showed no statistically significant differences in eradication rates by location, treatment duration, or patient type. There was evidence of significant statistical heterogeneity among trials in the Western Hemisphere (I2=55%), trials with 10 day treatment duration (I2=65.2%), and trials of patients with ulcers (I2=51.6%).
There were no statistically significant differences in compliance rates or side effects between the two therapies.
There was no evidence of publication bias.
Quadruple and triple therapy for the primary treatment of H. pylori infection resulted in similar, suboptimal eradication rates, and similar patient compliance and side effects.
The review question and supporting inclusion criteria were clearly defined. A comprehensive literature search was performed but it was unclear whether there were language restrictions, and language bias could not be ruled out completely. There was no evidence of publication bias. Data extraction was performed in duplicate, but it was unclear whether this was true for study selection, so reviewer error and bias could not be ruled out.
Study validity did not appear to have been assessed, which could have impacted on the robustness of the subsequent conclusions. There was evidence of statistical heterogeneity and, although the authors attempted to identify the sources of heterogeneity, subgroup analyses could not account for this. The authors acknowledged methodological and clinical differences among trials.
Although the authors’ conclusions appeared to reflect the evidence, given the limitations with the review process and the heterogeneity among the included trial, they should be interpreted with some caution.
Three reviewers acknowledged conflicts of interests, with links to various pharmaceutical companies.
Implications of the review for practice and research
Practice: The authors did not state any implications for practice.
Research: The authors stated that more effective alternative treatment strategies need to be developed and validated.
Unrestricted grant from Axcan (gastrointestinal medicine manufacturer).
Luther J, Higgins PD, Schoenfeld PS, Moayyedi P, Vakil N, Chey WD. Empiric quadruple vs triple therapy for primary treatment of Helicobacter pylori infection: systematic review and meta-analysis of efficacy and tolerability. American Journal of Gastroenterology 2010; 105(1): 65-73
Subject indexing assigned by NLM
Amoxicillin /therapeutic use; Antacids /therapeutic use; Anti-Bacterial Agents /therapeutic use; Anti-Infective Agents /therapeutic use; Bismuth /therapeutic use; Clarithromycin /therapeutic use; Drug Therapy, Combination; Helicobacter Infections /drug therapy; Helicobacter pylori; Humans; Metronidazole /therapeutic use; Outcome Assessment (Health Care); Patient Compliance; Practice Guidelines as Topic; Proton Pump Inhibitors /therapeutic use; Randomized Controlled Trials as Topic; Tetracycline /therapeutic use
Database entry date
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.