BACKGROUND: Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens. METHODS: This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables. RESULTS: As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups. CONCLUSION: The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance. TRIAL REGISTRATION ClinicalTrials.gov, ChiCTR 1900023646.
Humans ; Bismuth/therapeutic use* ; Metronidazole/therapeutic use* ; Esomeprazole/pharmacology* ; Minocycline/pharmacology* ; Helicobacter pylori ; Potassium Citrate/therapeutic use* ; Anti-Bacterial Agents ; Tetracycline/adverse effects* ; Helicobacter Infections/drug therapy* ; Drug Therapy, Combination ; Amoxicillin

BACKGROUND/AIMS: Ten-day sequential therapy has been evaluated as the first line therapy for Helicobacter pylori eradication but studies on sequential therapy as a second line therapy is lacking. The aim of this study was to compare the efficacy of 10-day sequential therapy and quadruple therapy as second line treatment for H. pylori eradication after failure of standard triple therapy. METHODS: Patients who did not respond to standard triple therapy for H. pylori eradication were assigned to either 10-day sequential or bismuth based quadruple therapy as second line treatment from January 2009 to December 2014 at Yeungnam University Medical Center. Post treatment H. pylori status was determined by rapid urease test, giemsa staining, or 13C-urea breath test. Eradication rate and side effects of both therapies were compared. RESULTS: A total of 158 H. pylori infected patients were included and 70 patients were treated by bismuth based quadruple therapy and 88 patients by 10-day sequential therapy. Age and sex were not significantly different between the two groups. Eradication rate was 84.3% (59/70) in quadruple group and 56.8% (50/88) in sequential group. Side effects occurred significantly higher in quadruple group than sequential group (27.1% vs. 11.4%, p=0.011). CONCLUSIONS: For second line H. pylori eradication after failure of standard triple therapy, bismuth based quadruple therapy showed significantly higher H. pylori eradication rate than 10-day sequential therapy. Further prospective studies are needed to evaluate the efficacy of 10-day sequential therapy as a second line H. pylori eradication treatment.
Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/adverse effects/pharmacology/*therapeutic use ; Bismuth/adverse effects/pharmacology/*therapeutic use ; Diarrhea/etiology ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy ; Helicobacter pylori/drug effects ; Humans ; Male ; Middle Aged ; Proton Pump Inhibitors/adverse effects/pharmacology/therapeutic use ; Retrospective Studies ; Risk Factors ; Taste Disorders/etiology ; Treatment Outcome ; Young Adult

Korea and Japan show the highest incidence of gastric cancer and Helicobacter pylori infection. New 2013 guidelines on H. pylori infection differ between the two countries with regard to the indications for H. pylori eradication, diagnostic methods, and treatment regimens. Indications for eradication in Korean guideline focus on specific diseases such as peptic ulcer disease, low-grade gastric mucosa-associated lymphoid tissue lymphoma, and after resection of early gastric cancer, while Japanese guideline includes all H. pylori-associated gastritis for the prevention of dissemination. With regard to the diagnosis, either noninvasive or invasive method (except for bacterial culture) is recommended in Korea, while two noninvasive tests including serum anti-H. pylori IgG antibody level are preferred in Japan. As for the treatment regimens, second-line treatment (quadruple bismuth-containing regimen) is recommended without first-line triple therapy in areas of high clarithromycin resistance in Korea. However, there is no bismuth-based second-line treatment in Japan, and the Japanese regimen consists of a lower dose of antibiotics for a shorter duration (7 days). Such discrepancies between the two countries are based not only on the differences in the literature search and interpretation, but also on the different approvals granted by the national health insurance system, manufacturing process of the antibiotics, and diagnostic techniques in each country. Collaborations are required to minimize the discrepancies between the two countries based on cost-effectiveness.
Anti-Bacterial Agents/pharmacology/*therapeutic use ; Antibodies/blood ; Bismuth/pharmacology/therapeutic use ; Disease Eradication/trends ; Drug Administration Schedule ; Guidelines as Topic ; Helicobacter Infections/complications/diagnosis/*drug therapy ; *Helicobacter pylori/drug effects/immunology ; Humans ; Japan ; Lymphoma, B-Cell, Marginal Zone/complications/surgery ; Republic of Korea ; Stomach Neoplasms/complications/surgery