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Abstract：
BACKGROUND: High-dose dual therapy (HDDT) can attain acceptable eradication rates provided that the optimal doses, timing and treatment duration are applied. The existing evidence still shows inconsistent reports (< 90%) on HDDT therapy except in some Asian countries. We aimed to assess and compare the efficacy of 14-day HDDT by comparing it to 14-day rabeprazole-containing hybrid therapy (HT) and to investigate the host and bacterial factors predicting the treatment outcomes of eradication therapies.
METHODS: In this open-label, randomized controlled trial, we recruited 243 naïve Helicobacter pylori-infected patients from September 1, 2018, to November 30, 2021. They were randomly allocated (1:1) to the HDDT group (rabeprazole 20 mg and amoxicillin 750 mg q.i.d for 14 days, n = 122) and the HT group (rabeprazole 20 mg and amoxicillin 1 g b.i.d. for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg b.i.d. for 7 days, n = 121). Twelve patients were absent during follow-up in the HDDT group and 4 in the HT group, resulting in 110 for the HDDT group and 117 for HT group in the per protocol (PP) study. The outcome was determined by urea breath tests 8 weeks later.
RESULTS: The eradication rates for the HDDT and HT groups were 77.0% (95% confidence interval [CI]: 68.5% to 84.1%) and 94.2% (95% CI: 88.4% to 97.6%) (P < 0.001) in intention-to-treat analysis; 85.5% (95% CI: 77.5% to 91.5%) and 97.4% [95% CI: 92.6% to 99.5%] (P = 0.001) in per protocol analysis. The adverse event rates were 7.3% in the HDDT group and 14.5% in the HT group (P = 0.081). The habit of coffee drinking was the dependent factor for eradication failure in the HDDT group (88.2% vs. 68.8%, P = 0.040), but had no influence in the HT group (97.9% versus 95.0%, P = 0.449) in the univariate analysis.
CONCLUSIONS: This study demonstrated that 14-day rabeprazole-containing HDDT did not achieve > 90% eradication rates for first-line H. pylori eradication as 14-day rabeprazole-containing HT did. HDDT is a potentially beneficial combination, which involves only two drugs with mild adverse effects; more precise studies are urged to find answers regarding these failures. This clinical trial was registered retrospectively on 28 November, 2021, as ClinicalTrials.gov identifier: NCT05152004.
METHODS: In this open-label, randomized controlled trial, we recruited 243 naïve Helicobacter pylori-infected patients from September 1, 2018, to November 30, 2021. They were randomly allocated (1:1) to the HDDT group (rabeprazole 20 mg and amoxicillin 750 mg q.i.d for 14 days, n = 122) and the HT group (rabeprazole 20 mg and amoxicillin 1 g b.i.d. for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg b.i.d. for 7 days, n = 121). Twelve patients were absent during follow-up in the HDDT group and 4 in the HT group, resulting in 110 for the HDDT group and 117 for HT group in the per protocol (PP) study. The outcome was determined by urea breath tests 8 weeks later.
RESULTS: The eradication rates for the HDDT and HT groups were 77.0% (95% confidence interval [CI]: 68.5% to 84.1%) and 94.2% (95% CI: 88.4% to 97.6%) (P < 0.001) in intention-to-treat analysis; 85.5% (95% CI: 77.5% to 91.5%) and 97.4% [95% CI: 92.6% to 99.5%] (P = 0.001) in per protocol analysis. The adverse event rates were 7.3% in the HDDT group and 14.5% in the HT group (P = 0.081). The habit of coffee drinking was the dependent factor for eradication failure in the HDDT group (88.2% vs. 68.8%, P = 0.040), but had no influence in the HT group (97.9% versus 95.0%, P = 0.449) in the univariate analysis.
CONCLUSIONS: This study demonstrated that 14-day rabeprazole-containing HDDT did not achieve > 90% eradication rates for first-line H. pylori eradication as 14-day rabeprazole-containing HT did. HDDT is a potentially beneficial combination, which involves only two drugs with mild adverse effects; more precise studies are urged to find answers regarding these failures. This clinical trial was registered retrospectively on 28 November, 2021, as ClinicalTrials.gov identifier: NCT05152004.
摘要：
背景：大剂量双重疗法（HDDT）可以达到可接受的根除率，前提是最佳剂量，应用时间和治疗持续时间。除一些亚洲国家外，现有证据仍显示有关HDDT治疗的报告不一致（<90％）。我们旨在通过将14天HDDT与14天含雷贝拉唑的混合疗法（HT）进行比较来评估和比较HDDT的疗效，并研究预测根除疗法治疗结果的宿主和细菌因素。
方法：在此开放标签中，随机对照试验,我们从2018年9月1日至2021年11月30日招募了243例未感染幽门螺杆菌的患者.他们被随机分配（1：1）到HDDT组（雷贝拉唑20mg和阿莫西林750mgq.i.d，持续14天，n=122）和HT组（雷贝拉唑20mg和阿莫西林1gb.i.d.持续7天，其次是雷贝拉唑20毫克，阿莫西林1克，克拉霉素500mg和甲硝唑500mgb.i.d.持续7天，n=121）。HDDT组随访期间12例患者缺席，HT组4例，在符合方案（PP）研究中，HDDT组为110，HT组为117。8周后通过尿素呼气试验确定结果。
结果：在意向治疗分析中，HDDT和HT组的根除率为77.0%（95%置信区间[CI]：68.5%至84.1%）和94.2%（95%CI：88.4%至97.6%）（P<0.001）；85.5%（95%CI：77.5%至91.5%）和99.7.4%[95%CI：92.6%]HDDT组和HT组的不良事件发生率分别为7.3%和14.5%(P=0.081)。饮用咖啡的习惯是HDDT组根除失败的依赖因素(88.2%vs.68.8%,P=0.040),但在HT组中没有影响(97.9%对95.0%，单变量分析中的P=0.449)。
结论：这项研究表明，14天含雷贝拉唑的HDDT一线根除幽门螺杆菌的根除率没有达到超过90%，14天含雷贝拉唑的HT的根除率。HDDT是一种潜在的有益组合，其中仅涉及两种具有轻度不良反应的药物；我们敦促进行更精确的研究以找到有关这些失败的答案。这项临床试验于11月28日进行了回顾性注册，2021年，作为ClinicalTrials.gov标识符：NCT05152004。
方法：在此开放标签中，随机对照试验,我们从2018年9月1日至2021年11月30日招募了243例未感染幽门螺杆菌的患者.他们被随机分配（1：1）到HDDT组（雷贝拉唑20mg和阿莫西林750mgq.i.d，持续14天，n=122）和HT组（雷贝拉唑20mg和阿莫西林1gb.i.d.持续7天，其次是雷贝拉唑20毫克，阿莫西林1克，克拉霉素500mg和甲硝唑500mgb.i.d.持续7天，n=121）。HDDT组随访期间12例患者缺席，HT组4例，在符合方案（PP）研究中，HDDT组为110，HT组为117。8周后通过尿素呼气试验确定结果。
结果：在意向治疗分析中，HDDT和HT组的根除率为77.0%（95%置信区间[CI]：68.5%至84.1%）和94.2%（95%CI：88.4%至97.6%）（P<0.001）；85.5%（95%CI：77.5%至91.5%）和99.7.4%[95%CI：92.6%]HDDT组和HT组的不良事件发生率分别为7.3%和14.5%(P=0.081)。饮用咖啡的习惯是HDDT组根除失败的依赖因素(88.2%vs.68.8%,P=0.040),但在HT组中没有影响(97.9%对95.0%，单变量分析中的P=0.449)。
结论：这项研究表明，14天含雷贝拉唑的HDDT一线根除幽门螺杆菌的根除率没有达到超过90%，14天含雷贝拉唑的HT的根除率。HDDT是一种潜在的有益组合，其中仅涉及两种具有轻度不良反应的药物；我们敦促进行更精确的研究以找到有关这些失败的答案。这项临床试验于11月28日进行了回顾性注册，2021年，作为ClinicalTrials.gov标识符：NCT05152004。
