Optimal Treatment Duration of Bismuth Quadruple Therapy for Helicobacter Pylori Eradication in Female Patients and Comparison of the Efficacy with That of Male Patients
试验速览
- 阶段
- 4 期
- 状态
- Enrolling By Invitation
- 入组人数
- 661
- 试验地点
- 1
- 主要终点
- The successful eradication rate
研究概览
简要总结
Helicobacter pylori eradication can reduce the risk of gastric cancer and decrease the recurrence of ulcers. However, in recent years, the increasing antibiotic resistance of Helicobacter pylori has reduced the efficacy of clarithromycin-based triple therapy to below 80%. The recent studies, including real-world data and a clinical trial, have consistently found that females have poorer eradication rate of Helicobacter pylori as compared with males. In previous clinical trial, investigators discovered that the efficacy of a 10-day bismuth quadruple therapy was not inferior to a 14-day bismuth quadruple therapy. However, it remains to be investigated whether the 10-day bismuth quadruple therapy is still non-inferior to the 14-day regimen in females.
This project continues the clinical trial to investigate whether the efficacy of the 10-day bismuth quadruple therapy in females is inferior to that in males and whether the 14-day bismuth quadruple therapy is superior to the 10-day regimen in females. The ultimate goal is to establish that male patients can use the 10-day bismuth quadruple therapy with fewer side effects and without compromising efficacy as compared with the 14-day regimen; while female patients are recommended to use the 14-day bismuth quadruple therapy as it would be more effective than the 10-day regimen.
Considering sex in research is becoming increasingly important, as females have more antibiotic-resistant Helicobacter pylori infection than males. The bismuth quadruple therapy can overcome most resistance issues. Researching and comparing the difference in the efficacy of bismuth quadruple therapy for Helicobacter pylori eradication between females and males are of significant clinical importance and align with current research trends.
详细描述
The recently published real-world study on Helicobacter pylori treatment, revealing that female (odds ratio 2.41 [95% confidence interval (CI) 1.16-5.03], P = 0.02) and age-Charlson Comorbidity Index ≥ 2 (odds ratio 3.16 [1.05-9.48], P = 0.04) were two independent factors for the failure of sequential therapy in eradicating Helicobacter pylori. The main cause of eradication failure is antibiotic resistance of the bacteria. Previous studies have found that females had more antibiotic-resistant Helicobacter pylori infections as compared with males did. In Australia and Italy, female was a predictor of metronidazole resistance; in Japan and Korea, female was a predictor of clarithromycin resistance; and among Alaskan Natives and in China, female predicted resistance to both metronidazole and clarithromycin.
The recent clinical trial found that the efficacy of a 10-day bismuth quadruple therapy was non-inferior to a 14-day bismuth quadruple therapy (Intention-to-treat analyses, 92.4% [95% (CI): 88.2%-96.5%] vs. 92.9% [95% CI: 88.9%-97.0%], absolute difference: -0.6%, lower boundary of the one-sided 97.5% CI: -6.7%, P = 0.020). However, subgroup analyses for males and females showed that while the 10-day therapy remained non-inferior to the 14-day therapy in males (95.2% [95% CI: 90.6%-99.8%] vs. 94.0% [95% CI: 88.4%-99.7%], absolute difference: 1.2%, lower boundary of the one-sided 97.5% CI: -6.8%, P = 0.022), it could not be demonstrated as non-inferior in females (89.2% [95% CI: 82.1%-96.3%] vs. 92.1% [95% CI: 86.5%-96.3%], absolute difference: -3.0%, lower boundary of the one-sided 97.5% CI: -12.3%, P = 0.198).
Previous research has identified female as a factor in the failure of 7-day clarithromycin-based triple therapy or concomitant therapy for Helicobacter pylori eradication. However, it is still uncertain whether female is a factor for Helicobacter pylori eradication failure with bismuth quadruple therapy.
In recent years, analyzing research results separately for females and males has become a trend. Historically, gender and sex differences were often overlooked in research design, conduct, and reporting, limiting the generalizability and applicability of findings to clinical practice. Heidari et al. have also advocated for the establishment of basic principles for international guidelines to encourage interdisciplinary research to systematically report sex and gender differences. The Sex and Gender Equity in Research (SAGER) guidelines recommend that researchers provide information on sex and gender in research design, data analysis, and result interpretation.
Given consecutive findings that females may have lower Helicobacter pylori eradication rates than males, designing a study to compare the efficacy of different durations of bismuth quadruple therapy between sexes is of significant clinical importance and aligns with current research trends.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are > 18 years
- •H. pylori infection confirmed by histology of a gastric biopsy, a positive rapid urease test, or a positive 13C-urea breath test.
排除标准
- •History of H. pylori eradication
- •Previous allergic reactions to any drugs in the bismuth quadruple therapy
- •Severe comorbidities
- •Pregnant or breastfeeding women
研究组 & 干预措施
The 10-day bismuth-based quadruple therapy group for females
The female patients receive a 10-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Fuliclin 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.
干预措施: Esomeprazole 40mg (Drug)
The 10-day bismuth-based quadruple therapy group for females
The female patients receive a 10-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Fuliclin 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.
干预措施: Metronidazole 250 MG (Drug)
The 10-day bismuth-based quadruple therapy group for females
The female patients receive a 10-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Fuliclin 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.
干预措施: Tetracycline Pill (Drug)
The 14-day bismuth-based quadruple therapy group for females
The female patients receive a 14-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Fuliclin 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.
干预措施: Esomeprazole 40mg (Drug)
The 14-day bismuth-based quadruple therapy group for females
The female patients receive a 14-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Fuliclin 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.
干预措施: Metronidazole 250 MG (Drug)
The 14-day bismuth-based quadruple therapy group for females
The female patients receive a 14-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Fuliclin 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.
干预措施: Tetracycline Pill (Drug)
The 10-day bismuth-based quadruple therapy group for males
The male patients receive a 10-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Fuliclin 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.
干预措施: Esomeprazole 40mg (Drug)
The 10-day bismuth-based quadruple therapy group for males
The male patients receive a 10-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Fuliclin 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.
干预措施: Metronidazole 250 MG (Drug)
The 10-day bismuth-based quadruple therapy group for males
The male patients receive a 10-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Fuliclin 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.
干预措施: Tetracycline Pill (Drug)
结局指标
主要结局
The successful eradication rate
时间窗: About 4 to 6 weeks after receiving the H. pylori eradication regimen
The patients stop taking the proton pump inhibitor and antibiotics for 4 to 6 weeks, and then they receive 13C-urea breath test or an H. pylori stool antigen test to confirm successful eradication or not. The successful rate is represented with a percentage (%).
次要结局
- Adherence to medications of the bismuth-based quadruple therapy(Since 1st day to 4 weeks after receiving the H. pylori eradication regimen)
- Adverse effects of the bismuth-based quadruple therapy(Since 1st day to 4 weeks after receiving the H. pylori eradication regimen)