Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial.

BACKGROUND: Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects. METHODS: An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period. RESULTS: The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. CONCLUSION: The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CLINICAL TRIALS REGISTRATION: CTR20230643.

Fourteen-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication in an area with high clarithromycin and levofloxacin resistance: a prospective randomized study (VQ-HP trial).

Potassium-competitive acid blockers (P-CABs) provide potent acid inhibition, yet studies on P-CAB-based quadruple therapy for H. pylori eradication are limited. We theorized that integrating bismuth subsalicylate into a quadruple therapy regimen could enhance eradication rates. However, data on the efficacy of vonoprazan bismuth quadruple therapy are notably scarce. Therefore, the aim of this study was to evaluate the efficacy of vonoprazan-based bismuth quadruple therapy in areas with high clarithromycin and levofloxacin resistance. This was a prospective, single-center, randomized trial conducted to compare the efficacy of 7-day and 14-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication between June 1, 2021, and March 31, 2022. Qualified patients were randomly assigned to the 7-day or 14-day regimen (1:1 ratio by computer-generated randomized list as follows: 51 patients for the 7-day regimen and 50 patients for the 14-day regimen). The regimens consisted of vonoprazan (20 mg) twice daily, bismuth subsalicylate (1024 mg) twice daily, metronidazole (400 mg) three times daily, and tetracycline (500 mg) four times daily. CYP3A4/5 genotyping and antibiotic susceptibility tests were also performed. Successful eradication was defined as 13negative C-UBTs 4 weeks after treatment. The primary endpoint was to compare the efficacy of 7-day and 14-day regimens as first-line treatments, which were assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. The secondary endpoints included adverse effects. A total of 337 dyspeptic patients who underwent gastroscopy were included; 105 patients (31.1%) were diagnosed with H. pylori infection, and 101 patients were randomly assigned to each regimen. No dropouts were detected. The antibiotic resistance rate was 33.3% for clarithromycin, 29.4% for metronidazole, and 27.7% for levofloxacin. The CYP3A4 genotype was associated with 100% rapid metabolism. The H. pylori eradication rates for the 7-day and 14-day regimens were 84.4%, 95% CI 74.3-94.2 and 94%, 95% CI 87.4-100, respectively (RR difference 0.25, 95% CI 0.03-0.53, p value = 0.11). Interestingly, the 14-day regimen led to 100% eradication in the clarithromycin-resistant group. Among the patients in the 7-day regimen group, only two exhibited resistance to clarithromycin; unfortunately, neither of them achieved a cure from H. pylori infection. The incidence of adverse events was similar in both treatment groups, occurring in 29.4% (15/51) and 28% (14/50) of patients in the 7-day and 14-day regimens, respectively. No serious adverse reactions were reported. In conclusion, 14 days of vonoprazan-based bismuth quadruple therapy is highly effective for H. pylori eradication in areas with high levels of dual clarithromycin and levofloxacin resistance.

Application of cefuroxime in the eradication therapy of Helicobacter pylori infection: A review article.

BACKGROUND: Helicobacter pylori infection and its associated diseases represent a significant global health concern. Patients who cannot use amoxicillin pose a therapeutic challenge and necessitate alternative medications. Preliminary research indicates that cefuroxime demonstrates promising potential for eradicating H. pylori infection, and there is a lack of comprehensive review articles on the use of cefuroxime. MATERIALS AND METHODS: This study conducts a thorough systematic literature review and synthesis. A comprehensive systematic search was conducted in PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Data up to January 13, 2024. The search strategy utilized the following keywords: (Cefuroxime) AND (Helicobacter pylori OR Helicobacter nemestrinae OR Campylobacter pylori OR Campylobacter pylori subsp. pylori OR Campylobacter pyloridis OR H. pylori OR Hp) for both English and Chinese language publications. Sixteen studies from five different countries or regions were included in final literature review. RESULTS: Analysis results indicate that H. pylori is sensitive to cefuroxime, with resistance rates similar to amoxicillin being relatively low. Regimens containing cefuroxime have shown favorable eradication rates, which were comparable to those of the regimens containing amoxicillin. Regarding safety, the incidence of adverse reactions in cefuroxime-containing eradication regimens was comparable to that of amoxicillin-containing regimens or other bismuth quadruple regimens, with no significant increase in allergic reactions in penicillin-allergic patients. Regarding compliance, studies consistently report high compliance rates for regimens containing cefuroxime. CONCLUSION: Cefuroxime can serve as an alternative to amoxicillin for the patients allergic to penicillin with satisfactory efficacies, safety, and compliance.

Meta-analysis of Helicobacter pylori eradication therapy using vonoprazan as an acid suppressor compared with bismuth quadruple therapy.

BACKGROUND: Vonoprazan, a novel acid suppressant, has recently emerged as a regimen for eradicating Helicobacter pylori. However, uncertainties exist about the effectiveness and safety of VPZ-based regimens compared with those of bismuth-based quadruple therapy in eradicating H. pylori. The present meta-analysis was performed to compare the effectiveness and safety of vonoprazan-based regimens with those of bismuth quadruple therapy in eradicating H. pylori. MATERIALS AND METHODS: All randomized controlled trials and non-randomized controlled trials comparing the vonoprazan-based therapy with the bismuth quadruple therapy were included in this meta-analysis. Information was also extracted by two evaluators, and if heterogeneity existed, a random-effects model was used to calculate the combined relative ratio and 95% confidence interval; otherwise, a fixed-effects model was used. And subgroup analyses were performed to explore the sources of heterogeneity. RESULTS: A total of 10 studies, comprising 2587 patients were included in the meta-analysis. The results showed that the combined eradication rate of patients treated with the vonoprazan-based regimen was significantly higher than that of patients treated with bismuth quadruple therapy, in both intention-to-treat and per-protocol analyses, and the differences were statistically significant. Among the intention-to-treat analyses results: (90.28% vs. 83.64% [odds ratio (OR) = 1.85, 95% confidence interval (CI) (1.27, 2.70), p = 0.001]); in the per-protocol analyses: (94.80% vs. 89.88%, [OR = 2.25, 95% CI (1.37, 3.69), p = 0.001]). The occurrence of adverse events was significantly lower in patients treated with vonoprazan-based regimens than in those treated with bismuth quadruple therapy, (14.50% vs. 25.89%, [OR = 0.49, 95% CI (0.32, 0.75), p = 0.001]). CONCLUSIONS: For eradicating H. pylori, vonoprazan-based regimens are remarkably advantageous over bismuth quadruple therapy. Furthermore, vonoprazan-based regimens exhibit a lower rate of adverse events than bismuth quadruple therapy.

Helicobacter pylori Eradication Treatment in Older Patients.

Helicobacter pylori is the main etiopathogenetic factor of chronic gastritis, peptic ulcer disease and gastric cancer. The world's population is shifting towards older people, who have the highest prevalence of H. pylori. Aging-related peculiarities could have an impact on the treatment of H. pylori and there is still a lack of research data in the older population. The aim of this review was to summarize the findings of the most recent information, publications and studies on the issues relating to H. pylori infection in older patients. H. pylori eradication offers gastrointestinal and extra gastrointestinal benefits in older patients. Based on the main guidelines, H. pylori should be eradicated independent of the patient's age, only reconsidering cases with terminal illness and low life expectancy. Proton pump inhibitors are generally safe and well tolerated. Some antibiotics require dose adjustment only in advanced renal insufficiency and the risk of hepatotoxicity is very low. Special precautions should be taken in patients with polypharmacy and those taking aspirin or non-steroidal anti-inflammatory drugs. In older patients, H. pylori eradication treatment frequently causes only mild and short-term adverse events; however, treatment compliance is usually still very good. H. pylori treatment in older patients does not increase the risk of Clostridium difficile infection. Optimal eradication effectiveness (> 90%) is mostly achieved with bismuth- and non-bismuth-based quadruple therapies. Susceptibility-guided treatment of H. pylori can contribute to increasing the effectiveness of eradication regimens in older adults. To achieve optimal H. pylori eradication effectiveness in older patients, the same guidelines, which are applied to adults, also apply to this population: avoiding repetitive treatment prescriptions, choosing quadruple therapies, prescribing longer treatment duration and administering high-dose proton pump inhibitors twice daily.

Ten-Day Vonoprazan-Amoxicillin Dual Therapy vs Standard 14-Day Bismuth-Based Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Multicenter Randomized Clinical Trial.

INTRODUCTION: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. METHODS: This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori -infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13 C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. RESULTS: Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% ( P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% ( P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% ( P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group ( P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group ( P < 0.001), while not in the B-quadruple group ( P = 0.110). DISCUSSION: The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. TRAIL REGISTRATION NUMBER: ChiCTR2300070100.

Vonoprazan-amoxicillin dual therapy versus bismuth-containing quadruple therapy for Helicobacter pylori eradication: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Recently, vonoprazan-amoxicillin (VA) dual therapy has been reported as a promising approach for Helicobacter pylori (H. pylori) eradication. However, the effects of VA therapy versus bismuth-containing quadruple therapy (BQT) on H. pylori eradication remains unclear. The objective of this meta-analysis was to compare the effects of VA dual therapy with BQT for H. pylori eradication. METHODS: A comprehensive search of the literature was conducted from the beginning to September 2023, utilizing PubMed, Embase, the Cochrane Library and Web of Science database. A random-effects model was used to perform a meta-analysis to determine the pooled relative risk (RR) with 95% confidence intervals (CIs). Moreover, trial sequential analysis (TSA) was conducted to evaluate the conclusiveness of the H. pylori eradication rate. RESULTS: Six randomized controlled trials (RCTs) with 1233 patients were included. The VA therapy has similar eradication rate (ITT analysis: 87% vs. 85.7%, RR = 1.01, 95% CI: 0.93-1.09, p = 0.84; PP analysis: 92.5% vs. 93.2%, RR = 1.00, 95% CI: 0.94-1.06, p = 0.97) and compliance (RR = 1.01, 95% CI: 0.99-1.03, p = 0.32) compared to BQT. The VA therapy group had a significantly lower incidence of total adverse events than the BQT group (16.3% vs. 40.0%, RR = 0.45, 95% CI: 0.37-0.55, p < 0.00001). The TSA result showed that the effect was conclusive. CONCLUSIONS: Current evidence indicated that VA therapy is just as successful as BQT in eliminating H. pylori, yet it has fewer adverse events and similar compliance.

Bismuth-Based Therapy: The New Therapy for Obese Patients Undergoing Gastric Bypass Surgery?

AIMS: Our aim was to assess, in obese patients undergoing Roux-en Y gastric bypass surgery, the bismuth quadruple therapy (BQT) eradication rates at the first-line Helicobacter pylori (Hp) treatment as proposed by the Maastricht V/Florence consensus in areas with high clarithromycin (CLT) resistance rates-10 days proton pump inhibitor bid and three-in-one single capsule bismuth therapy containing bismuth, metronidazole, and tetracycline, marketed as Pylera four times a day. METHODS: This is a single-center prospective study over a 3-year period. Endoscopy and Hp assessment by histology was performed at baseline, and posttreatment Hp status was assessed by C13 urea breath test 4-6 weeks after the end of therapy. Data analysis was performed using the IBM® SPSS® Statistics 28.0 (IBM Corp. 2021, Armonk, NY) using mostly nonparametric comparisons (α = 0.05). RESULTS: The study cohort consisted of 598 adult obese Hp-positive patients [476, 78.6% female, age 43.2 (± 10.4) years] consecutively scheduled for Hp eradication therapy. Hp was eradicated in 500 patients [83.6.3% (95% CI: 80.4%-86.5%)], and the eradication was independent of gender, age, endoscopic diagnosis, and smoking status (p > 0.05). CONCLUSION: Ten days of BQT did achieve Maastricht V/Florence recommended first-line eradication rates (at least 80%) in obese Portuguese patients undergoing Roux-en Y gastric bypass, being by now the most reliable choice for Hp eradication.

The Efficacy and Safety of Regimens for Helicobacter pylori Eradication Treatment in China: A Systemic Review and Network Meta-Analysis.

BACKGROUND: With Helicobacter pylori's increasing antibiotic resistance, evidence of more effective treatments is lacking in China, where H. pylori prevalence is nearly 50%. Thus, we performed a network meta-analysis to compare therapeutic regimens. METHODS: Data extracted from eligible randomized controlled trials from January 2000 to September 2021 were entered into a Bayesian hierarchical random-effects model to evaluate the efficacy and safety of H. pylori eradication regimens. RESULTS: This study included 101 trials involving 21,745 patients. Vonoprazan-bismuth-containing quadruple therapy (VBQT) ranked the highest [surfaces under cumulative ranking curve (SUCRA), 83.64%], followed by high-dose amoxicillin dual therapy (HDDT) [SUCRA, 79.70%, odds ratio (OR)=1.31, 95% credible interval (CrI) (0.36, 4.72)] and proton pump inhibitor-based bismuth-containing quadruple therapy (BQT) [SUCRA, 63.59%, OR=1.59, 95% CrI (0.48, 5.24)]. HDDT [OR=2.47, 95% CrI (1.51, 4.06)], BQT [OR=2.04, 95% CrI (1.69, 2.47)], concomitant quadruple nonbismuth therapy (CT) [OR=1.93, 95% CrI (1.19, 3.15)], and sequential therapy (ST) [OR=1.86, 95% CrI (1.50, 2.32)] had higher eradication rates than standard triple therapy (TT). ST (SUCRA, 82.52%) and VBQT (SUCRA, 83.89%) had the highest eradication rate before and after 2010 in the effectiveness ranking, respectively. Furthermore, the H. pylori eradication rate of patients receiving 14-day BQT treatment was higher than that of 10-day BQT regimen [OR=2.55, 95% CI (1.84, 3.53)] and 7-day BQT regimen [OR=3.64, 95% CI (2.64, 5.01)]. CONCLUSIONS: The TT regimen was not an optimal choice in China for H. pylori eradication; VBQT, HDDT, and BQT showed better efficacy. After 2010, there is a trend toward significance that VBQT provided a higher H. pylori eradication rate in China, but with only 1 randomized controlled trial. Thus, more supportive real-world data are needed to confirm its effectiveness.

Optimal treatment duration of bismuth-containing quadruple therapy in Helicobacter pylori infection: A retrospective study.

The use of bismuth-containing quadruple therapy (BQT) in Helicobacter pylori eradication has been increasing. Although the recommended treatment length for BQT is 14 days, longer durations may be associated with higher rates of adverse events. The aim of this study was to evaluate the optimal duration of BQT by comparing eradication rates and adverse events among 7, 10, and 14-day regimens. A total of 328 patients treated with BQT at Seoul National University Hospital from January 2010 to May 2022 were retrospectively evaluated. The eradication rates of different treatment groups were compared using intention-to-treat (ITT) and per-protocol (PP) analyses. Baseline characteristics of the enrolled patients and adverse events were also analyzed. A total of 74, 177, and 77 patients were included in the 7-, 10-, and 14-day groups, respectively. Forty-one patients were lost during the follow-up. The eradication rates were 71.6%, 84.2%, and 80.5% (P = .106) by ITT, and 84.1%, 94.9%, and 92.5% (P = .028) by PP analysis in the 7-, 10-, and 14-day groups, respectively. The 10-day regimen showed significantly higher eradication rates than the 7-day regimen in both ITT (P = .024) and PP (P = .018) analyses. However, there were no significant differences in eradication rates between the 10- and 14-day groups in either ITT (P = .667) or PP (P = .537) analysis. Adverse event incidence was comparable among the groups (P = .835). Treatment with BQT for 10 days was as effective as 14 days without increasing the adverse events.

Efficacy and safety of probiotic-supplemented bismuth quadruple therapy for the treatment of Helicobacter pylori infection: a systematic review and meta-analysis.

OBJECTIVE: We performed a meta-analysis to determine whether the addition of probiotics to the bismuth quadruple therapy (BQT) for Helicobacter pylori would improve the incidence of eradication and reduce that of side effects. METHODS: Randomized controlled trials matching the inclusion criteria were collected from PubMed, Embase, Web of Science, and The Cochrane Central Register of Controlled Trials. A Mantel-Haenszel random-effects model was used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for the incidences of eradication rate, side effects as a whole, diarrhea, and other side effects. RESULTS: Ten studies were selected for inclusion in the meta-analysis. The pooled RRs for the eradication rates in intention-to-treat and per-protocol analyses of the probiotic group vs. the control group were 1.07 (95% CI: 1.02-1.11) and 1.04 (95% CI: 1.00-1.07), respectively. Probiotic supplementation reduced the incidences of side effects (RR 0.58, 95% CI: 0.37-0.91), diarrhea (RR 0.41, 95% CI: 0.25-0.67), and bitter taste (RR 0.63, 95% CI: 0.40-0.99). CONCLUSIONS: The results of this meta-analysis support the use of probiotics in combination with BQT in the clinical management of patients with H. pylori infection.

EFFICACY AND SAFETY OF GEMIFLOXACIN CONTAINING TREATMENT REGIMEN IN FIRST-LINE TREATMENT OF HELICOBACTER PYLORI.

•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse effects were fewer and milder in the gemifloxacin group. •Since treatment period was shorter and pills to be taken were fewer compared to quadruple treatment, patient compliance was significantly higher in the gemifloxacin group. Background - After eradication of Helicobacter pylori (H. pylori) chronic gastritis will resolve, complications due to H. pylori infection and recurrence of infection will be prevented. Objective - To determine efficacy and safety of gemifloxacin containing treatment regimen in first line treatment of H. pylori with comparison to bismuth containing quadruple therapy. Methods - This retrospective study was conducted in a tertiary care university hospital between January 2018 and January 2021 with 410 participants who were diagnosed to have H. pylori infection with biopsies obtained during upper gastrointestinal system endoscopy. Patients were distributed into two groups according to their first-line treatment regimens. First group patients were treated with amoxicillin, gemifloxacin and pantoprazole and second group patients were treated with amoxicillin, metronidazole, bismuth subcitrate and pantoprazole for seven days. Results - Intention to treat and per protocol ratios for gemifloxacin containing regimen were 90.0% and 91.2%, while quadruple treatment has these ratios as 91.7% and 93.8% respectively. Treatment success rate in both regimens were similar. But adverse effects were lower and patient compliance were better in patients who had gemifloxacin containing treatment (P<0.001). Conclusion - Gemifloxacin containing treatment regimen is as effective as bismuth containing quadruple treatment regimen for H. pylori infection and patient compliance is better in this group. Gemifloxacin containing treatment regimens may be novel and effective alternatives for eradication of H. pylori infection.

Pharmacokinetics, Safety, and Tolerability of Vonoprazan- or Esomeprazole-Based Bismuth-Containing Quadruple Therapy: A Phase 1, Double-Blind, Parallel-Group Study in Adults with Helicobacter pylori Infection in China.

Quadruple therapy comprising 2 antibiotics, a proton pump inhibitor, and bismuth, is recommended for Helicobacter pylori eradication in China. This Phase 1, double-blind, parallel-group study aimed to evaluate the pharmacokinetics, safety, and tolerability of bismuth-containing vonoprazan- or esomeprazole-based quadruple therapy in H. pylori-positive healthy subjects at a single site in China. Quadruple therapy comprising vonoprazan 20 mg or esomeprazole 20 mg with bismuth potassium citrate 600 mg (equivalent to bismuth 220 mg), clarithromycin 500 mg, and amoxicillin 1000 mg was administered twice daily for 2 weeks. Forty-four subjects were enrolled, 22 each in the vonoprazan (mean age, 34.5 years; men, 63.6%) and esomeprazole (mean age, 31.6 years; men, 59.1%) groups. Day 14 bismuth plasma pharmacokinetic parameters area under the plasma concentration-time curve during a dosing interval (geometric mean ratio, 1.07 [90% confidence interval, 0.82-1.40]) and maximum observed plasma concentration (geometric mean ratio, 1.30 [90% confidence interval, 0.94-1.81]) were similar between the treatment groups. At Day 42 follow-up, 100% and 94.4% of subjects were H. pylori negative in the vonoprazan and esomeprazole groups, respectively. The incidence of treatment-emergent adverse events was similar between the groups, with no serious adverse events. No new safety concerns were identified. In conclusion, vonoprazan had no significant effect on plasma bismuth exposure compared with esomeprazole.

Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Vonoprazan-based triple and dual therapy versus bismuth-based quadruple therapy for Helicobacter pylori infection in China: a three-arm, randomised clinical trial protocol.

BACKGROUND: Helicobacter pylori infection and associated diseases are a growing global public health issue. H. pylori infection is the major cause of gastric cancer, over 90% of duodenal ulcers, and over 70% of gastric ulcers. The infection rate of H. pylori is approximately 50%, and approximately 50% of new cases of gastric cancer worldwide occur in China. Bismuth (BI)-based quadruple therapy is recommended as the first-line treatment for H. pylori in China. Vonoprazan (VPZ), a new potassium-competitive acid blocker that can inhibit gastric acid secretion more effectively than proton pump inhibitors (PPIs), has been combined with antibiotics to effectively eradicate H. pylori. In this study, we compared the efficacy and safety of two VPZ-based therapies with that of BI-based therapy for H. pylori treatment. METHODS: A three-armed randomised controlled trial (RCT) is being conducted in Shenzhen, with 327 participants recruited from the Gastroenterology Clinic of the University of Hong Kong-Shenzhen Hospital. Patients were diagnosed with H. pylori infection based on a positive 13C-urea breath test (UBT). Patients are kept naïve to their treatment and are randomly assigned in a 1:1:1 ratio to either VPZ-based triple, VPZ-based dual, or BI-based quadruple therapy for 14 days. All groups are subjected to follow-up evaluations of safety, adverse drug reactions, and clinical variables in the first, second, and fourth weeks after treatment. Successful eradication is confirmed by a negative 13C-UBT six weeks after treatment. If initial treatment fails, (1) those patients are turned to another regimen, or (2) a drug resistance test is conducted, after which an individualised treatment regimen shall be prescribed according to antimicrobial susceptibility testing. The resulting data will be evaluated using intention-treat and a per-protocol analysis. DISCUSSION: This study is the a RCT aims to evaluate the efficacy and safety of 14-day VPZ-based triple and dual therapies in comparison with BI-based quadruple therapy. The outcomes of this study may allow treatment recommendations and update drug instructions in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=141314.

Colloidal bismuth pectin-containing quadruple therapy as the first-line treatment of Helicobacter pylori infection: A multicenter, randomized, double-blind, non-inferiority clinical trial.

BACKGROUND: Bismuth-containing quadruple therapy is an effective regimen for Helicobacter pylori (H. pylori) treatment. No head-to-head comparison trials have been conducted to evaluate the efficacy of colloidal bismuth pectin (CBP) in quadruple therapy for eradicating H. pylori. We aimed to compare the efficacy and safety of CBP quadruple therapy and bismuth potassium citrate (BPC) quadruple therapy for 14 days in the first-line treatment of H. pylori. METHODS: In this multicenter, randomized, double-blind, non-inferiority clinical trial, H. pylori-infected subjects without eradication history were randomized to receive amoxicillin 1 g twice daily, tetracycline 500 mg three time daily, esomeprazole 20 mg twice daily in combination with CBP 200 mg three time daily or BPC 240 mg twice daily for 14 days. 13 C-urea breath tests were used to access the eradication rate at least 4 weeks after treatment. RESULTS: Between April 2021 and July 2022, 406 patients were assessed for eligibility and 339 subjects were randomized. The cure rates (primary outcome) of CBP and BPC quadruple therapy were 90.5% and 92.3% (p = 0.56) by intention-to-treat analysis, respectively, and 96.1% and 96.2% (p = 1.00) by per-protocol analysis, respectively. CBP quadruple therapy was non-inferior to BPC quadruple therapy in the intention-to-treat and per-protocol analysis (p < 0.025). The frequency of adverse events and compliance were not different among the two groups (p > 0.05). CONCLUSIONS: Both CBP and BPC quadruple therapy for 14 days provide high efficacy, good compliance, and safety in the first-line treatment of H. pylori in China.

Comparing high-dose dual therapy with bismuth-containing quadruple therapy for the initial eradication of Helicobacter pylori infection on Hainan Island: A randomized, multicenter clinical trial.

BACKGROUND: Traditional bismuth-containing quadruple therapy, as a first-line eradication treatment for Helicobacter pylori (H. pylori), has several disadvantages, including drug side effects, low medication adherence, and high costs. Trials of high-dose dual treatment have demonstrated its advantages, which include good safety and adherence profiles. In this study, we investigated the efficacy, safety, and compliance of a high-dose dual therapy when compared with bismuth-based quadruple treatment for the initial eradication of H. pylori infection on Hainan Island, China. METHODS: We randomized 846 H. pylori-infected patients into two groups. A bismuth-containing quadruple therapy group was administered the following: esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily, and colloidal bismuth pectin in suspension 150 mg three times/day for 2 weeks. A high-dose dual therapy group was administered the following: esomeprazole 20 mg four times/day and amoxicillin 1000 mg three times/day for 2 weeks. Patients were given a 13C urea breath test at 4 weeks at treatment end. Adverse effects and compliance were evaluated at follow-up visits. RESULTS: Eradication rates in the high-dose dual therapy group were: 90.3% (381/422, 95% confidence interval [CI]: 87.1%-92.9%) in intention-to-treat (ITT) and 93.6% (381/407, 95% CI: 90.8%-95.8%) in per-protocol (PP) analyses. Eradication rates were 87.3% in ITT (370/424, 95% CI: 83.7%-90.3%) and 91.8% in PP analyses (370/403, 95% CI: 88.7%-94.3%) for quadruple therapy, with no statistical differences (P = 0.164 in ITT and P = 0.324 in PP analyses). Adverse effects were 13.5% (55/407) in the dual group and 17.4% (70/403) in the quadruple group (P = 0.129). Compliance was 92.4% (376/407) in the dual group and 86.6% (349/403) in the quadruple group (P = 0.007). CONCLUSIONS: High-dose dual therapy had high eradication rates comparable with bismuth-based quadruple treatment, with no differences in adverse effects, however higher adherence rates were recorded.

Minocycline vs. tetracycline in bismuth-containing quadruple therapy for Helicobacter pylori rescue treatment: a multicentre, randomized controlled trial.

BACKGROUND: To compare the efficacy and tolerability of minocycline vs. tetracycline in bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) rescue treatment. METHODS: This study was a multi-center, randomized-controlled, non-inferiority trial. Refractory H. pylori-infected subjects with multiple treatment-failure were randomly (1:1) allocated to receive 14-day therapy with esomeprazole 20 mg b.i.d, bismuth 220 mg b.i.d, plus metronidazole 400 mg q.i.d and minocycline 100 mg b.i.d (minocycline group) or tetracycline 500 mg q.i.d (tetracycline group). Primary outcome was H. pylori eradication rate evaluated by 13C-urea breath test at least 6 weeks after the end of treatment. Antibiotic resistance was determined using E test method. RESULTS: Three hundred and sixty-eight subjects were randomized. The eradication rates in minocycline group and tetracycline group were 88.0% (162/184, 95% CI 83.3-92.8%) and 88.6% (163/184, 95% CI 83.9-93.2%) in intention-to-treat analysis, 98.0% (149/152, 95% CI 95.8-100%) and 97.4% (150/154, 95% CI 94.9-99.9%) in per-protocol analysis, 93.1% (162/174, 95% CI 89.3-96.9%) and 93.1% (163/175, 95% CI 89.4-96.9%) in modified intention-to-treat analysis. Minocycline, tetracycline and metronidazole resistance rates were 0.7%, 1.4% and 89.6%, respectively. Non-inferiority of minocycline was confirmed (P < 0.025). Metronidazole resistance did not affect the efficacy of either therapy. The two therapies exhibited comparable frequencies of adverse events (55.4% vs. 53.3%); almost half of them were mild. Dizziness was the most common adverse events in the minocycline group. CONCLUSIONS: Minocycline can be an alternative for tetracycline in bismuth-containing quadruple therapy for H. pylori empirical rescue treatment, irrespective of metronidazole resistance. However, relatively high incidence of adverse events in both regimens should be emphasized.

Comparison of 10 and 14 days of antofloxacin-based versus 14 days of clarithromycin-based bismuth quadruple therapy for Helicobacter pylori eradication: A randomized trial.

OBJECTIVE: Our team previously reported the use of antofloxacin-based bismuth quadruple therapy for the eradication of Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of 10 and 14 days of antofloxacin-based versus 14 days of clarithromycin-based bismuth quadruple therapy in the first-line treatment for H. pylori infection. METHODS: 1174 patients with H. pylori infection were randomized into three groups: 10-days and 14-days antofloxacin (ANT10 and ANT14) groups who received 10 and 14 days of antofloxacin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and antofloxacin 200 mg q.d.), 14-days clarithromycin (CLA14) group who received 14 days of clarithromycin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.). Eradication rate, antibiotic resistance and adverse events were analyzed. RESULTS: The intention-to-treat (ITT) and per-protocol (PP) analyses have showed statistically different eradication rates between ANT14 group and ANT10 group (ITT p = 0.001; PP p < 0.001), but no statistical difference between ANT10 group and CLA14 group (ITT p = 0.340; PP p = 0.092). Treatment regimen, drug resistance and therapy duration were important clinical factors related to H. pylori eradication rates in multivariate logistic analysis. Longer durations had significantly higher eradication rates in patients with antibiotic-resistant strains or antibiotic-susceptible strains. The incidences of nausea and bitter taste were significantly higher in CLA group compared with ANT group (p = 0.002 for nausea; p = 0.002 for bitter taste). The ANT10 and ANT14 group had similar adverse event rates of gastrointestinal reactions. CONCLUSION: The study showed that the H. pylori eradication rate with ANT14 therapy was higher than that with ANT10 and CLA14 therapy without significantly increasing the rates of adverse event. 14 days of antofloxacin-based bismuth quadruple therapy may be a more effective way as the first-line treatment for H. pylori infection.