Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke-Universtität, Magdeburg, Germany.
Lancet. 2011 Mar 12;377(9769):905-13. doi: 10.1016/S0140-6736(11)60020-2. Epub 2011 Feb 21.
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.
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 (13)C 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.
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.
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.
Axcan Pharma Inc.
幽门螺杆菌与上消化道的良性和恶性疾病有关，且抗生素耐药性的增加使得有必要采用替代疗法。我们的目的是评估一种新的、单胶囊治疗方案与幽门螺杆菌根除的金标准相比的疗效和安全性。
我们在欧洲的 39 个地点进行了一项随机、开放标签、非劣效性、3 期试验，比较了 10 天的四联疗法（奥美拉唑加一种包含枸橼酸铋钾、甲硝唑和四环素的三合一单胶囊）与 7 天的奥美拉唑、阿莫西林和克拉霉素（标准疗法）在记录有幽门螺杆菌感染的成年人中的疗效和安全性。根据 Quintiles Canada（加拿大魁北克省圣劳伦特市）独立生成的预定清单，患者按照治疗方案进行随机分组。我们的研究设计为非劣效性试验，但有能力检测优越性。我们的主要结局是通过在治疗结束后至少 28 天和 56 天进行两次阴性（13）C 尿素呼气试验来确定幽门螺杆菌根除。我们在方案人群中进行了非劣效性评估，并在意向治疗人群中进行了随后的优越性评估（即所有随机分配治疗的参与者）。本研究在 ClinicalTrials.gov 注册，编号为 NCT00669955。
12 名参与者失访，101 名参与者被排除在方案人群分析之外。在方案人群（n=339）中，四联疗法的治疗下限置信区间大于预先设定的 -10%非劣效性边界（95%CI 15·1-32·3；p<0·0001）。在意向治疗人群（n=440）中，四联疗法组的根除率为 80%（174 名参与者中的 174 名），标准疗法组为 55%（123 名参与者中的 123 名）（p<0·0001）。两种治疗方法的安全性相似；主要不良事件为胃肠道和中枢神经系统疾病。
鉴于克拉霉素耐药幽门螺杆菌的患病率上升，四联疗法应被视为一线治疗，因为四联疗法在提供更高的根除率的同时，具有与标准疗法相似的安全性和耐受性。
Axcan Pharma Inc.
