Tai Wei-Chen, Yang Shih-Cheng, Yao Chih-Chien, Wu Cheng-Kun, Liu An-Che, Lee Chen-Hsiang, Kuo Yuan-Hung, Chuah Seng-Kee, Liang Chih-Ming
Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833, Taiwan.
Chang Gung University College of Medicine, Taoyuan City, Taiwan.
Infect Dis Ther. 2023 May;12(5):1415-1427. doi: 10.1007/s40121-023-00811-3. Epub 2023 May 3.
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.
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.
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.
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.
高剂量双联疗法（HDDT）只要采用最佳剂量、给药时间和疗程，就能达到可接受的根除率。除了一些亚洲国家外，现有证据对于HDDT疗法的报道仍不一致（<90%）。我们旨在通过将14天的HDDT与含雷贝拉唑的14天混合疗法（HT）进行比较，评估和比较其疗效，并研究预测根除疗法治疗效果的宿主和细菌因素。
在这项开放标签的随机对照试验中，我们从2018年9月1日至2021年11月30日招募了243例初治幽门螺杆菌感染患者。他们被随机分配（1:1）至HDDT组（雷贝拉唑20mg和阿莫西林750mg，每日4次，共14天，n = 122）和HT组（雷贝拉唑20mg和阿莫西林1g，每日2次，共7天，随后雷贝拉唑20mg、阿莫西林1g、克拉霉素500mg和甲硝唑500mg，每日2次，共7天，n = 121）。HDDT组有12例患者在随访期间失访，HT组有4例，因此在符合方案（PP）研究中，HDDT组有110例，HT组有117例。8周后通过尿素呼气试验确定结果。
在意向性分析中，HDDT组和HT组的根除率分别为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）；在符合方案分析中分别为85.5%（95%CI：77.5%至91.5%）和97.4%[95%CI：92.6%至99.5%]（P = 0.001）。HDDT组的不良事件发生率为7.3%，HT组为14.5%（P = 0.081）。在单因素分析中，咖啡饮用习惯是HDDT组根除失败的相关因素（88.2%对68.8%，P = 0.040），但在HT组中没有影响（97.9%对95.0%，P = 0.449）。
本研究表明，含雷贝拉唑的14天HDDT用于一线幽门螺杆菌根除时，未能像含雷贝拉唑的14天HT那样达到>90%的根除率。HDDT是一种潜在有益的联合方案，仅涉及两种药物且不良反应较轻；迫切需要更精确的研究来找出这些失败的原因。本临床试验于2021年11月28日进行回顾性注册，ClinicalTrials.gov标识符：NCT05152004。
