Yan Tian-Lian, Wang Jing-Hua, Zhu Ren-Ke, Zhai Hao-Liang, Wang Zhen-Zhen, Mao Xin-Li, Shen Xian, Xu Ping, Ma Dan, He Xin-Jue, Wang Jie-Wei, Gao Jian-Guo, Jiang Ling-Ling, Sun Kefang, Chen Ye, Sang Jian-Zhong, Liu Xiao-Qin, Chen Jiao-E, Li Lan
Department of Gastroenterology, Zhejiang Provincial Clinical Research Center for Digestive Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Gastroenterology, Haining People's Hospital, Haining, China.
Helicobacter. 2025 Jul-Aug;30(4):e70056. doi: 10.1111/hel.70056.
Rescue treatment for non-naive patients with persistent Helicobacter pylori (H. pylori) infection is lacking, especially in areas where tetracycline is unavailable. This trial aimed to evaluate the efficacy and safety of replacing proton pump inhibitor (PPI) with potassium-competitive acid blocker (P-CAB) in bismuth quadruple therapy (BQT) containing amoxicillin and furazolidone as rescue therapy.
We conducted a prospective, open-label, noninferiority randomized controlled trial at six institutions in eastern China. A total of 444 patients with a history of H. pylori treatment failure were enrolled and randomly assigned in a 1:1 ratio to either the 14-day P-CAB-BQT group (vonoprazan 20 mg, colloidal bismuth 200 mg, amoxicillin 1000 mg and furazolidone 100 mg, all given twice daily) or the 14-day PPI-BQT group (rabeprazole 10 mg given twice daily, and the same dose of three other drugs as the 14-day P-CAB-BQT group). The primary endpoint was the eradication rate assessed by C urea breath test. The secondary endpoints were adverse events and compliance.
H. pylori eradication rates of PPI-BQT versus P-CAB-BQT group were 83.8% versus 91.9% in the intention-to-treat (ITT) analysis (treatment difference: 8.1%; 95% CI: 2.1%-14.1%; non-inferiority p < 0.001, p-value for difference = 0.008); 86.1% versus 95.8% in the modified ITT (MITT) analysis (treatment difference: 9.7%; 95% CI: 4.4%-15.0%; non-inferiority p < 0.001, p-value for difference < 0.001); and 86.3% versus 95.6% in the per-protocol (PP) analysis (treatment difference: 9.3%; 95% CI: 3.8%-14.8%; non-inferiority p < 0.001, p-value for difference < 0.001). The P-CAB-BQT regimen was shown to be non-inferior to the PPI-BQT regimen and yielded higher eradication rates across all analysis populations (ITT, MITT, and PP). The overall frequency of adverse events (27.9% and 34.2%, p = 0.151) and compliance (93.7% and 94.6%, p = 0.686) were similar between PPI and P-CAB groups. Among the patients suspected of drug-induced fever (8.6% and 7.2%, p = 0.597), 82.9% experienced fever after administration of furazolidone for > 10 days. The eradication rates were not affected by prior choice of antibiotics and the number of treatment attempts.
The 14-day P-CAB-BQT therapy containing amoxicillin and furazolidone provided a satisfactory eradication rate and a good safety profile as rescue treatment for H. pylori eradication, regardless of prior choice of antibiotics and the number of treatment attempts. Shortening the treatment course to 10-11 days could prevent the majority of drug-induced fevers.
对于曾接受过治疗但仍持续感染幽门螺杆菌（H. pylori）的患者，缺乏有效的挽救治疗方案，尤其是在无法获取四环素的地区。本试验旨在评估在含阿莫西林和呋喃唑酮的铋剂四联疗法（BQT）中，用钾离子竞争性酸阻滞剂（P-CAB）替代质子泵抑制剂（PPI）作为挽救治疗的疗效和安全性。
我们在中国东部的6家机构进行了一项前瞻性、开放标签、非劣效性随机对照试验。共纳入444例有幽门螺杆菌治疗失败史的患者，按1:1比例随机分为14天P-CAB-BQT组（沃克20mg、胶体铋200mg、阿莫西林1000mg和呋喃唑酮100mg，均每日2次）或14天PPI-BQT组（雷贝拉唑10mg每日2次，其他三种药物剂量与14天P-CAB-BQT组相同）。主要终点是通过碳-尿素呼气试验评估的根除率。次要终点是不良事件和依从性。
在意向性分析（ITT）中，PPI-BQT组与P-CAB-BQT组的幽门螺杆菌根除率分别为83.8%和91.9%（治疗差异：8.1%；95%CI：2.1%-14.1%；非劣效性p<0.001，差异p值=0.008）；在改良意向性分析（mITT）中分别为86.1%和95.8%（治疗差异：9.7%；95%CI：4.4%-15.0%；非劣效性p<0.001，差异p值<0.001）；在符合方案分析（PP）中分别为86.3%和95.6%（治疗差异：9.3%；95%CI：3.8%-14.8%；非劣效性p<0.001，差异p值<0.001）。结果表明，P-CAB-BQT方案不劣于PPI-BQT方案，且在所有分析人群（ITT、mITT和PP）中均有更高的根除率。PPI组和P-CAB组不良事件的总体发生率（分别为27.9%和34.2%，p=0.151）和依从性（分别为93.7%和94.6%，p=0.686）相似。在疑似药物性发热的患者中（分别为8.6%和7.2%，p=0.597），82.9%在服用呋喃唑酮>10天后出现发热。根除率不受先前抗生素选择和治疗尝试次数的影响。
含阿莫西林和呋喃唑酮的14天P-CAB-BQT疗法作为幽门螺杆菌根除的挽救治疗，无论先前的抗生素选择和治疗尝试次数如何，均能提供令人满意的根除率和良好的安全性。将疗程缩短至10 - 11天可预防大多数药物性发热。
