Rifabutin-Based Triple Therapy (RHB-105) for Helicobacter pylori Eradication A Double-Blind, Randomized, Controlled Trial
Rifabutin-Based Triple Therapy (RHB-105) for Helicobacter pylori Eradication A Double-Blind, Randomized, Controlled Trial
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DOI：
10.7326/m19-3734
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发表时间：
2020-06-16
影响因子：
39.2
通讯作者：
Kalfus, Ira N.
中科院分区：
文献类型：
--
作者：
Graham, David Y.;Canaan, Yamil;Kalfus, Ira N.
背景资料：虽然共识支持根除幽门螺杆菌感染，抗菌药物耐药性已大大降低根除率与大多数当前therapy.Objective：为了评估一种新的利福布丁为基础的治疗（RHB-105）的有效性为幽门螺杆菌根除。设计：3期，双盲试验（ERADICATE Hp 2）。（Clinical Trials.gov：NCT 03198507）设置：美国55个临床研究中心。参与者：455名未经治疗的患有上腹部不适和确诊幽门螺杆菌感染的成人。干预：RHB-105（阿莫西林，3g;奥美拉唑，120 mg;和利福布雷定，150 mg）与活性对照药物（阿莫西林，3g和奥美拉唑，120 mg），每8小时给予4粒胶囊，持续14天。治疗后4周通过C-13尿素呼气试验证明幽门螺杆菌根除率的组间差异，并使用卡方检验进行分析。在意向治疗人群中，RHB-105的根除率高于活性对照药物（分别为228 vs. 227例患者; 83.8% [95% CI，78.4%至88.0%] vs. 57.7% [95% CI，51.2%至64.0%]; P < 0.001）。根除率不受克拉霉素或甲硝唑耐药性的影响。未检测到利福必利耐药。最常报告的不良事件（发病率>= 5%）为腹泻（RHB-105组10.1% vs.活性对照药物组7.9%），头痛（7.5% vs. 7.0%）和恶心（4.8% vs. 5.3%）。局限性：排除亚洲血统的人，因为他们的细胞色素P450 2C 19代谢不良的患病率较高。这些发现表明RHB-105作为一线经验性幽门螺杆菌治疗的潜力，解决了当前抗生素耐药性增加环境中未满足的需求。
Background: Although consensus supports eradication of Helicobacter pylori infections, antimicrobial resistance has substantially reduced eradication rates with most current therapies.Objective: To assess the effectiveness of a novel rifabutin-based therapy (RHB-105) for H pylori eradication.Design: Phase 3, double-blind trial (ERADICATE Hp2). (Clinical Trials.gov: NCT03198507)Setting: 55 clinical research sites in the United States.Participants: 455 treatment-naive adults with epigastric discomfort and confirmed H pylori infection.Intervention: RHB-105 (amoxicillin, 3 g; omeprazole, 120 mg; and rifabutin, 150 mg) versus active comparator (amoxicillin, 3 g, and omeprazole, 120 mg), given as 4 capsules every 8 hours for 14 days.Measurements: Between-group difference for H pylori eradication rate, demonstrated by C-13 urea breath test 4 weeks after treatment, analyzed by using the chi(2) test.Results: In the intention-to-treat population, the eradication rate was higher with RHB-105 than with the active comparator (228 vs. 227 patients, respectively; 83.8% [95% CI, 78.4% to 88.0%] vs. 57.7% [95% CI, 51.2% to 64.0%]; P < 0.001). Eradication rates were unaffected by resistance to clarithromycin or metronidazole. No rifabutin resistance was detected. The most commonly reported adverse events (incidence >= 5%) were diarrhea (10.1% with RHB-105 vs. 7.9% with active comparator), headache (7.5% vs. 7.0%), and nausea (4.8% vs. 5.3%).Limitation: Persons of Asian descent were excluded because of their higher prevalence of poor cytochrome P450 2C19 metabolizers.Conclusion: These findings suggest potential for RHB-105 as first-line empirical H pylori therapy, addressing an unmet need in the current environment of increasing antibiotic resistance.