ヘリコバクターピロリ感染への4剤併用療法、
標準療法より除菌率優れる

文献:Malfertheiner P et al.Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy.The Lancet, Early Online Publication, 22 February 2011.

ヘリコバクターピロリ感染患者440人を対象に、4剤併用療法(オメプラゾール+ビスマス・メトロニダゾール・テトラサイクリン配合剤)の標準的な3剤併用療法に対する非劣性を無作為化比較試験で検証。PP解析で非劣性が示されたほか、ITT解析では4剤併用療法群の方が標準療法群より除菌率が高かった(80%対55%)。

Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial

Original Text

Background

Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments necessary. Our aim was to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication.

Methods

We did a randomised, open-label, non-inferiority, phase 3 trial in 39 sites in Europe, comparing the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) versus 7 days of omeprazole, amoxicillin, and clarithromycin (standard therapy) in adults with recorded H pylori infection. Patients were randomly assigned treatment according to a predetermined list independently generated by Quintiles Canada (Ville St-Laurent, QC, Canada). Our study was designed as a non-inferiority trial but was powered to detect superiority. Our primary outcome was H pylori eradication, established by two negative 13C urea breath tests at a minimum of 28 and 56 days after the end of treatment. Our assessment for non-inferiority was in the per-protocol population, with subsequent assessment for superiority in the intention-to-treat population (ie, all participants randomly assigned treatment). This study is registered with ClinicalTrials.gov, number NCT00669955.

Findings

12 participants were lost to follow-up and 101 were excluded from the per-protocol analysis. In the per-protocol population (n=339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of-10% (95% CI 15・1-32・3; p<0・0001). In the intention-to-treat population (n=440), eradication rates were 80% (174 of 218 participants) in the quadruple therapy group versus 55% (123 of 222) in the standard therapy group (p<0・0001). Safety profiles for both treatments were similar; main adverse events were gastrointestinal and CNS disorders.

Interpretation

Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori, especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy.

Funding

Axcan Pharma Inc.

2011.02.24 記事提供:m3.com