Concerns have been raised regarding the decreasing success rates of the standard treatment of Helicobacter pylori (proton pump inhibitor (PPI) and two/three antibiotics) and the long-term effects carried by PPI. Despite conflicting data, Tegoprazan, a potassium-competitive acid blocker, is hypothesized to be superior to PPI for eradicating H pylori. This systematic review and meta-analysis aim to determine the superiority of Tegoprazan-containing therapy to PPI-containing therapy for H pylori eradication.

A systematic literature search identified studies published until December 12, 2024, from MEDLINE, EMBASE, SCOPUS, and CENTRAL. The search strategy included the following keywords: "Tegoprazan," "Proton Pump Inhibitors," and "Helicobacter pylori." Only randomized controlled trials (RCTs) that compared the efficacy of Tegoprazan to any PPI were included. Risk of bias assessment was performed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs. The random-effect model was used to calculate the pooled risk ratio (RR) and its 95% Confidence Interval (95% CI) from the intention-to-treat population.

Six RCTs with low risks of bias were included in this meta-analysis. All studies included treatment-naïve patients and compared first-line H pylori treatment. The overall eradication rates of Tegoprazan-containing (N = 1052) versus PPI-containing therapy (N = 1058) were 83.37% and 80.06%, respectively (RR 1.045; 95% CI 1.008-1.084; I 2 = 0%). Tegoprazan-containing therapy demonstrated comparable treatment-emergent adverse event (TEAE) rates compared to PPI-containing therapy (46.48% vs. 46.31%; RR 1.026; 95% CI 0.952-1.106; I 2 = 48%).

This meta-analysis demonstrated that Tegoprazan-containing therapy is superior to PPI-containing therapy for first-line H pylori eradication, with comparable safety profiles.

Owing to the high prevalence of antibiotic resistance in Helicobacter pylori (H. pylori) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs. esomeprazole for H. pylori eradication in a patient population in China.

This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori, evaluated using a 13C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%.

The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles.

Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China.

ClinicalTrials.gov, NCT04198363.

Tegoprazan (TPZ), a potassium-competitive acid blocker with potent gastric acid-suppressing activity, may be a potential agent for treating Helicobacter pylori infection. The study aimed to evaluate the efficacy of TPZ-based therapy for H. pylori eradication compared with proton pump inhibitor (PPI)-based therapy.

A comprehensive literature search was conducted up to August 2024 using PubMed, Embase, and the Cochrane Library to investigate the beneficial effects of TPZ-based therapy for H. pylori eradication. Studies that evaluated the eradication rates between the TPZ- and PPI-based therapies were included. The authors conducted a meta-analysis to calculate the eradication rate and pooled risk ratio (RR) with a 95% confidence interval.

Seven studies involving 3200 patients were included. H. pylori eradication rates did not differ significantly between the TPZ- and PPI-based therapies based on the intention-to-treat (77.3% vs. 76.4%, p = 0.68; pooled RR = 1.01 [0.97-1.05]) and per-protocol (84.3% vs. 84.2%, p = 0.69; pooled RR = 1.01 [0.98-1.04]) analyses. Additionally, no significant difference was observed in the adverse drug events between TPZ- and PPI-based therapies (27.2% vs. 30.8%, p = 0.26; pooled RR = 0.91 [0.76-1.08]).

H. pylori eradication and adverse drug event rates with TPZ- and PPI-based treatments were similar.

To explore the current research status and trends of potassium-competitive acid blockers (P-CABs) in the treatment of acid related diseases (ARDs) using bibliometric analysis.

We collected publications related to P-CAB in the treatment of acid-related diseases in the Web of Science (WOS) Core Collection from the establishment of the database to 30 June 2024. We evaluated the publication volume and citation status over the years using the WOS platform, and visualized the authors, countries, institutions, keywords, and citations of the publications using CiteSpace and VOSviewer.

This study included a total of 455 articles. The number of publications and citations related to research has been increasing year by year. The results show that the scholars with the highest number of publications mainly come from South Korea and Japan. Scholars such as Geun Seog Song, Bongtae Kim, and Nobuhiro Inatomi produced many works in related fields. The most popular drug in this field was vonoprazan, and research on this drug mainly focused on the effectiveness and safety evaluation of ARDs such as Helicobacter pylori infection, gastroesophageal reflux disease, peptic ulcers, etc. Researchers were concerned about the evaluation of treatment regimens and efficacy comparison between P-CABs and traditional proton pump inhibitors (PPIs) in the treatment of ARDs. At the same time, researchers are also closely monitoring the potential adverse reactions and long-term adverse outcomes of clinical application of P-CABs for ARDs.

The clinical application of P-CABs, represented by vonoprazan, in ARDs is receiving widespread attention from researchers. The exploration of the application of this type of drug in ARDs is constantly expanding, and it is a research field with great clinical value and research potential.

Tegoprazan, a potassium-competitive acid blocker, can be used as a substitute for proton pump inhibitors in Helicobacter pylori eradication therapy; some studies have reported improved efficacy. In Korea, where clarithromycin resistance rates are high, we aimed to compare the efficacies of tegoprazan-based concomitant and bismuth quadruple therapies.

We retrospectively analyzed data from patients with H. pylori infection who received either 10-day tegoprazan-based concomitant therapy or 14-day tegoprazan-based bismuth quadruple therapy as first-line treatment. The primary outcome was H. pylori eradication rate, with secondary outcomes including adverse events and insufficient medication rates.

Among the 1082 patients included in the study, 620 and 462 were treated with tegoprazan-based concomitant and bismuth quadruple therapies, respectively. Intention-to-treat analysis demonstrated no difference in eradication rates between the tegoprazan-based concomitant and bismuth quadruple therapy groups (74.7% [95% confidence interval-CI, 71.1-78.0%] vs 74.7% [95% CI, 70.6-78.5%], P = 0.999). Per-protocol analysis also showed similar eradication rates between the two groups (88.0% [95% CI, 85.0-90.6%] vs 89.7% [95% CI, 86.3-92.5%], P = 0.424). The overall adverse event rates (49.6% vs 39.2%, P = 0.001) and insufficient medication rates (4.8% vs 2.4%, P = 0.036) were higher in the bismuth quadruple therapy group than in the concomitant therapy group.

The eradication rates of tegoprazan-based 10-day concomitant therapy and 14-day bismuth quadruple therapy were comparable. However, because of its shorter treatment duration, better medical adherence, and lower incidence of adverse events, tegoprazan-based concomitant therapy may be preferable in regions with high rates of clarithromycin and metronidazole resistance.

H. pylori eradication is effective for gastric cancer prevention. Treatment failure is caused by increased antibiotic resistance. This study aimed to determine eradication rates and perform cost analysis between susceptibility-guided therapy and empirical treatment in patients with H. pylori treatment failure.

This retrospective cohort study included patients with dyspepsia undergoing gastroscopy at tertiary care center in Thailand from March 2014 to October 2021. Treatment failure was defined as persistent H. pylori infection after ≥1 regimen completion. Early AST was defined as AST performed shortly after first-line treatment failure. Demographic data, AST results, eradication regimens, and medication costs were collected from database and reviewed.

Of 1080 patients with H. pylori infection, 315 had treatment failure (mean age 58.4 years; 44.4 % males). AST of 85 strains demonstrated resistance to levofloxacin (57.6 %), metronidazole (51.8 %), clarithromycin (44.7 %), and amoxicillin (4.7 %). In multivariate analysis, sequential therapy was significantly associated with treatment failure (OR 1.66; 95%CI 1.01-2.74, p = 0.045), whereas vonoprazan-containing therapy was related to treatment success (OR 1.60; 95%CI 1.04-2.48, p = 0.034). Medication nonadherence (OR 37.97; 95%CI 8.97-160.65, p < 0.001) contributed to treatment failure. Susceptibility-guided therapy provided better eradication rate than empirical therapy (97.5% vs. 65.5 %, OR 20.54; 95%CI 4.92-85.81, p < 0.001) in treatment failure group. Twenty-four patients had early AST, while 61 had AST after treatment failures. Most patients with early AST achieved treatment success by second-line eradication. Early AST provided significantly lower total average cost of treatment than group without AST ($368.2 vs. $402.0 per patient, p = 0.034) and AST after treatment failures ($368.2 vs. $752.8 per patient, p < 0.001). Early AST group had the lowest cost of subsequent medication, posttreatment urea breath test, and hospital visits.

Susceptibility-guided therapy provided significantly higher eradication rate than empirical therapy in patients with treatment failure. Early AST might be a cost-effective strategy for H. pylori eradication after failed therapy and can prevent unnecessary antibiotic use in Thailand.

Potassium-competitive acid blockers have emerged as a promising treatment of acid-related disorders. However, the optimal dosage for maximizing their efficacy remains unclear. The aim of this network meta-analysis was to compare the efficacy and safety of various dosages of potassium-competitive acid blockers and proton-pump inhibitors for treating acid-related disorders.

We searched PubMed, Embase, Cochrane Library, and Web of Science from inception to July 16, 2023. Data extraction was performed independently by 2 authors. The Cochrane Risk of Bias in Randomized Trials tool (RoB 2.0) was used for bias assessment. The efficacy and safety were compared using the odds ratio with 95% confidence intervals.

Twelve articles were included in the present meta-analysis. For gastric/duodenal ulcers, keverprazan 30 mg (K30) exhibited the highest surface under the cumulative ranking (SUCRA) value (92.8%) for healing rate. In terms of total adverse events, lansoprazole 30 mg (L30) exhibited the lowest SUCRA value (25.3%) in the treatment of gastric/duodenal ulcers. For the healing rate in erosive esophagitis, the maximum SUCRA value of vonoprazan 40 mg (V40) was 90.7% in the first subgroup (erosive esophagitis using vonoprazan, keverprazan, and lansoprazole) and the maximum SUCRA value of T50 was 72.1% in the second subgroup (erosive esophagitis using tegoprazan, fexuprazan, and esomeprazole). For the total adverse events in erosive esophagitis, L15 exhibited the lowest SUCRA value (12.2%) in the first group and E40 exhibited the lowest SUCRA value (24.4%) in the second group.

K30 may be the most effective dosage for increasing the healing rate of gastric/duodenal ulcers. For erosive esophagitis, V40 and T50 may be the preferred dosages.

The efficacy of Helicobacter pylori (H. pylori) eradication therapies encompassing one or more antibiotics and a proton pump inhibitor (PPI) has lately decreased. Vonoprazan (VPZ), a potassium-competitive acid blocker, provides higher gastric acid suppression than PPIs. We performed a meta-analysis evaluating the efficacy and safety of VPZ in H. pylori eradication therapies.

Studies were searched in PubMed, Embase, and the Cochrane Library up to June 2023. Efficacy was evaluated by intention-to-treat analysis. Data were combined by meta-analyzing risk differences (RD). Heterogeneity was evaluated by subgrouping.

Seventy-seven studies (24 randomized clinical trials) evaluated 44,162 patients (22,297 receiving VPZ and 21,865 PPIs). Overall VPZ efficacy was 88% (95% CI = 87%-90%): 86%, 88%, and 94% for dual/triple/quadruple-VPZ-containing therapies. VPZ efficacy was 87% (86%-89%) in first-line and 90% (87%-93%) in rescue therapy. VPZ performed better than PPIs in treatment-naïve patients (87% vs. 70%; RD = 0.13, 95% CI = 0.11-0.15) and when using triple regimens. No significant differences were observed in rescue and quadruple therapies. In patients with clarithromycin-resistant infection, VPZ-based therapies demonstrated an 81% efficacy (76%-85%), surpassing PPIs (76% vs. 40%; RD = 0.33, 95% CI = 0.24-0.43). For clarithromycin-susceptible strains, VPZ efficacy was 92% (89%-95%), similar to PPIs. VPZ adverse events rate was 19% (16%-21%), comparable to PPI-based regimens (18% vs. 13%, respectively; RD = 0.00, 95% CI = -0.01 to 0.02, p = 0.57).

The efficacy of VPZ-based regimens was over 85% in all treatment combinations. In treatment-naïve and clarithromycin-resistant patients, VPZ performed better than PPIs. In rescue therapy, in clarithromycin-susceptible patients or when quadruple regimens were prescribed, this advantage was not confirmed. Tolerability was similar in both regimens.

Acid suppression with proton pump inhibitors (PPIs) represents the standard of care in the treatment of acid-related diseases. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. The aims of this review are to summarize the current status and future development of the new class of antisecretory drugs (potassium-competitive acid blockers, P-CABs) that have recently been introduced into medical practice.

Over the past decades, clinical needs unmet by the current acid suppressants have been recognized, especially in the management of patients with GERD, Helicobacter pylori infection and NSAID-related peptic ulcer. The failure to address these needs is mainly due to their inability to achieve a consistent acid suppression in all patients and, particularly, to control nighttime acidity. It was then realized that an extended duration of acid suppression would exert additional benefits. The available data with P-CABs show that they are able to address these unmet clinical needs. Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available. However, only two of them are approved outside Asia. Vonoprazan is available in North, Central and South America while tegoprazan is marketed only in Latin American countries. Two other compounds (namely linazapran glurate and zestaprazan) are presently under clinical development. While clinical trials on GERD have been performed with all P-CABs, only vonoprazan and tegoprazan have been investigated as components of Helicobacter pylori eradication regimens. The available data show that-in the above two clinical indications-P-CABs provide similar or better efficacy in comparison with PPIs. Their safety in the short-term overlaps that of PPIs, but data from long-term treatment are needed.

The effectiveness of vonoprazan (VPZ)-based regimens in enhancing Helicobacter pylori (HP) eradication rates is promising. This study evaluated the clinical efficacy of 14-day VPZ-based triple therapy in obese patients infected with HP. A total of 200 obese patients with gastric disorders, confirmed to be HP-positive via gastroscopy and the 13C urea breath test, were retrospectively analyzed. Among them, 118 patients received the 14-day VPZ-based triple regimen (Study group), while 82 patients were treated with the traditional 14-day bismuth-containing proton pump inhibitor-based quadruple regimen (Control group). Baseline characteristics, pretreatment inflammatory indicators, lipid profiles, and gastrointestinal function indicators recorded. The two groups were compared for treatment efficacy, HP eradication rate, gastrointestinal function improvement, and incidence of adverse reactions. The Study group demonstrated a higher overall effective rate compared to the Control group, particularly in HP-strong positive obese patients. No significant differences were observed between the two groups for HP-positive obese patients in terms of total effective rate, HP eradication rate, gastrointestinal function improvement, or adverse reactions incidence. In conclusion, the 14-day VPZ-based triple regimen exhibited superior therapeutic efficacy, higher HP eradication rates, enhanced gastrointestinal function, and reduced adverse reactions in HP-strong positive obese patients, indicating improved overall efficacy and safety.

The aim of this study was to evaluate the effectiveness and safety of the nine most widely studied Vonoprazan (VPZ)-based treatment regimens along with traditional Proton pump inhibitor (PPI)-based treatment regimens in eradicating Helicobacter pylori (H. pylori) infection.

Through searching PubMed, Embase, Cochrane Library, Web of Science, we exclusively included randomized controlled trials (RCTs) to investigate the efficacy of VPZ-based and PPI-based therapies for H. pylori infection. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly.

The RCTs were collected from the earliest available date up to August 2023. Twenty-one RCTs were included, with a total sample size of 5481. The results of the network meta-analysis showed that the eradication rate of the VPZ-based quadruple 14-day (VPZ-Q14) treatment regimen in Intention-to-treat (ITT) analysis was the highest (SUCRA: 0.874); The eradication rate of the VPZ-based quadruple 10-day (VPZ-Q10) treatment plan in Per-protocol (PP) analysis was the highest (SUCRA: 0.849). All regimens were well tolerated without significant differences. According to the probability ranking of safety, high-dose VPZ-based dual 14-day therapy (H-VPZ-D14) ranked first in SUCRA, reaching 0.952. This indicates that H-VPZ-D14 treatment is the safest with a relatively low incidence of adverse effect. Therefore, VPZ-based therapies not only have a higher eradication rate, but also possess satisfactory safety.

Compared with traditional PPI-based therapies, VPZ-based therapies have shown superior eradication effects. Based on the Ranking Plot of the Network, the VPZ-Q14 or VPZ-Q10 treatment regimen for H. pylori has a higher eradication rate and acceptable differences compared to other treatment regimens. In addition, for regions with high antibiotic resistance rates, we recommend a 14-day quadruple therapy with bismuth based on VPZ.

A cure for Helicobacter pylori (H. pylori) remains a problem of global concern. The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide. Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy, tolerability and cost. The most common sequential therapy consists of a dual therapy [proton-pump inhibitors (PPIs) and amoxicillin] for the first period (5 to 7 d), followed by a triple therapy for the second period (PPI, clarithromycin and metronidazole). PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics, hence the idea of using new generation molecules.

To compare an optimized sequential therapy with the standard non-bismuth quadruple therapies of 10 and 14 d, in terms of efficacy, incidence of adverse effects (AEs) and cost.

This open-label prospective study randomized 328 patients with confirmed H. pylori infection into three groups (1:1:1): The first group received quadruple therapy consisting of twice-daily (bid) omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg for 10 d (QT-10), the second group received a 14 d quadruple therapy following the same regimen (QT-14), and the third group received an optimized sequential therapy consisting of bid rabeprazole 20 mg plus amoxicillin 1 g for 7 d, followed by bid rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the next 7 d (OST-14). AEs were recorded throughout the study, and the H. pylori eradication rate was determined 4 to 6 wk after the end of treatment, using the 13C urea breath test.

In the intention-to-treat and per-protocol analysis, the eradication rate was higher in the OST-14 group compared to the QT-10 group: (93.5%, 85.5% P = 0.04) and (96.2%, 89.5% P = 0.03) respectively. However, there was no statistically significant difference in eradication rates between the OST-14 and QT-14 groups: (93.5%, 91.8% P = 0.34) and (96.2%, 94.4% P = 0.35), respectively. The overall incidence of AEs was significantly lower in the OST-14 group (P = 0.01). Furthermore, OST-14 was the most cost-effective among the three groups.

The optimized 14-d sequential therapy is a safe and effective alternative. Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.

Antimicrobial therapy is necessary to eradicate Helicobacter pylori infection. The emergence of antimicrobial-resistant bacteria poses a threat to continued treatment with antimicrobial agents. For those who prescribe antimicrobial therapy, it is necessary to constantly monitor the emergence of antimicrobial-resistant bacteria.

H. pylori clinical isolates were collected in Japan from August 2018 to December 2020 for antimicrobial susceptibility testing. The agar dilution method was used for the determination of the minimum inhibitory concentration (MIC) of clarithromycin (CLR), amoxicillin (AMX), metronidazole (MNZ), and sitafloxacin (STX).

MICs for 938 H. pylori isolates were examined. The primary resistance rates of H. pylori clinical isolates for CLR, AMX, MNZ, and STX in Japan were 35.5%, 2.7%, 4.2%, and 27.6%, respectively. The primary resistance rates for CLR, AMX, and MNZ were significantly higher than those of the 2002-2005 isolates. The resistance rate for CLR was significantly higher in females (males: 30.7%, females: 41.5%, p < 0.001) and higher in the ≤29 years age group (54.8%) than in the other age groups, although there were no significant differences (p = 0.104). The MNZ resistance rate was significantly higher in the ≤29 years age group than in the other age groups (p = 0.004). The resistance rate for STX increased with age, but a significant difference was only seen between the 30-49 years age group and the ≥70 years age group (p < 0.001), and the resistance rate was significantly higher in strains isolated in the Kyushu region than in the other regions (p < 0.001).

The primary resistance rates for CLR, AMX, and MNZ of H. pylori clinical isolates in Japan were higher than those of the 2002-2005 isolates. Continuous surveillance is needed to monitor the trends in antimicrobial-resistant H. pylori.

While proton pump inhibitor (PPI) therapy has proven to be effective in managing gastroesophageal reflux disease (GERD), a notable portion of patients who experience GERD symptoms may not respond to this treatment. Research suggests that roughly 30% of individuals with a presumed GERD diagnosis may continue to experience symptoms, whether partially or completely, even when receiving PPI therapy. The aim of this study was to assess the treatment of gastrointestinal diseases with a novel potassium-competitive acid blocker (P-CAB), vonoprazan, in terms of its effectiveness and safety in the Pakistani population.

This prospective, multicenter, observational study was conducted in Pakistan. This study included 1,642 patients from January 2023 to August 2023, aged 18 years, with gastrointestinal disorders. All demographic data, medical history, GERD severity assessment questionnaire (GerdQ), and laboratory parameters, including stool assessment for Helicobacter pylori (H. pylori), were observed. Patients were orally treated with vonoprazan at doses of 10 mg or 20 mg, once or twice daily. Statistical analysis was done by one-way ANOVA.

Out of 1,642 patients, 840 (51.2%) were males and 802 (48.8%) were females, with a mean age of 39.81±14.61 years. The mean GerdQ score at baseline was 20.37±15.87, 7.24±8.15 at the second week of treatment, and 3.70±6.31 at the fourth week of treatment (p<0.001). 90.74% of patients achieved H. pylori eradication. Most patients were acid regurgitation and heartburn-free for >70% of days. Most of the patients, 1,283 (78.13%), exhibited good treatment compliance. Mild adverse events were reported in 37 (2.3%) patients.

The use of vonoprazan significantly reduced the likelihood of GERD by improving symptoms and was also highly effective in the elimination of H. pylori infections. Vonoprazan was generally well tolerated.

To describe the pharmacology, efficacy, safety, and potential role of vonoprazan with amoxicillin or amoxicillin and clarithromycin for the treatment of Helicobacter pylori infection in adults.

PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched using the terms: (vonoprazan OR voquezna) AND ("H. pylori" OR "Helicobacter pylori") AND amoxicillin with no date limitations up to November 3, 2022.

Studies assessing the efficacy and safety of vonoprazan with amoxicillin and/or clarithromycin were included and divided into 3 groups based on different comparisons between treatment regimens used in each group.

Ten clinical trials and 17 observational studies were included. Vonoprazan-based therapy demonstrated greater acid inhibition and similar or higher efficacy than proton-pump inhibitor (PPI)-based therapy in treatment-naïve patients and with clarithromycin-resistant infections.

Proton-pump inhibitor-based therapies have not reached the desired successful eradication rate of 90% for H. pylori infection. Vonoprazan-based therapies being at least as effective as PPI-based therapies offer an alternative for patients with H. pylori infection.

Vonoprazan-based therapies were effective and well tolerated for the treatment of H. pylori infection in adults. These regimens provide an important alternative with prolonged acid inhibition, lower potential for CYP2C19 polymorphism, and at least comparable efficacy and safety versus PPI-based therapies in patients with H. pylori infections. Thus, vonoprazan-based therapy should be considered for certain patients, for example, those with failure to PPI-based treatments.

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.

With the increase in antibiotic resistance, the success rate of Helicobacter pylori (H. pylori) eradication therapy has declined in recent years. Vonoprazan-amoxicillin (VA) dual therapy has been reported to be a promising regimen.

To compare the efficacy and safety of VA dual therapy and bismuth quadruple therapy containing amoxicillin and clarithromycin for H. pylori first-line eradication, and to further analyze the effects of clarithromycin resistance on eradication rate.

This study was a single-center, open-label, randomized controlled trial.

Treatment-naïve H. pylori-infected patients were randomly allocated 1:1 to the VA group (vonoprazan 20 mg twice daily and amoxicillin 750 mg four times daily, for 14 days) or the RBAC group (rabeprazole 10 mg, bismuth potassium citrate 220 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily, for 14 days). H. pylori clarithromycin resistance and CYP2C19 gene polymorphisms were detected with real-time polymerase chain reaction (PCR) technique. The eradication rates and adverse events were analyzed.

A total of 151 patients were enrolled. The intention-to-treat (ITT), modified intention-to-treat (mITT), and per-protocol (PP) eradication rates and their 95% confidence intervals (95% CIs) were 94.6% (86.0-98.3%), 98.6% (91.3-99.9%), and 98.5% (90.9-99.9%) for VA group and 87.0% (77.0-93.3%), 91.8% (82.3-96.6%), and 93% (83.7-97.4%) for RBAC group. The eradication rate of the VA group was noninferior to the RBAC group in ITT, mITT, and PP analyses (p < 0.0001). In patients infected with strains of clarithromycin resistance point mutation, the eradication rate of the RBAC group decreased to lower than 90%, but the difference from the VA group did not achieve statistical significance (ITT eradication rate: 81.5% in the RBAC group and 96.2% in the VA group, p = 0.192). The incidence of adverse events in the VA group was 39.2%, which was significantly lower than that in the RBAC group (79.2%, p = 0.000).

The efficacy of VA dual therapy is noninferior to RBAC in H. pylori first-line eradication, with fewer adverse reactions.

This study was registered at the Chinese Clinical Trial Registry (ChiCTR2100052550) on 30 October 2021.

This research aimed to evaluate the eradication efficacy, safety, and gastrointestinal symptom relief rates of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy in primary eradication patients in Yangzhou, China. It also investigated the possible factors influencing the success of different Helicobacter pylori eradication regimens. A single-center, prospective, open-label, randomized controlled study was performed from December 2020 and October 2021, in which 255 patients with H. pylori infection were assigned in a 1:1:1 ratio to the three different groups. Our results showed that high-dose dual therapy (91.0%, 71/78) and resistance gene-based triple therapy (94.9%, 75/79) achieved eradication rates and compliance equivalent to those of empirical bismuth quadruple therapy (85.3%, 64/75) in the per-protocol analysis, while high-dose dual therapy had lower rates of adverse events (11.5%, 9/78, P < 0.05), fewer side effects, and greater safety. Most patients' gastrointestinal discomfort symptoms improved after eradication of H. pylori. Poor compliance (P < 0.05) and antibiotic resistance (P < 0.05) were risk factors for the efficacy of H. pylori eradication. Therefore, the appropriate regimen can be individualized for eradication therapy in clinical practice according to the patient's resistance and tolerance to the drug.

Resistance of Helicobacter pylori (H. pylori) to antibiotics has reached alarming levels worldwide, and the efficacy of the H. pylori eradication treatment has decreased dramatically because of antibiotic resistance. To gain a more comprehensive understanding of the development status, research hotspots, and future trends related to H. pylori antibiotic resistance, we conducted a thorough retrospective analysis via the bibliometrics method. We searched the Science Citation Index Expanded of the Web of Science Core Collection for all pertinent articles on H. pylori antibiotic resistance from 2013 to 2022. R-bibliometrix, CiteSpace, and VOSviewer tools were utilized to depict statistical evaluations in order to provide an unbiased presentation and forecasts in the field. We incorporated a total of 3,509 articles related to H. pylori antibiotic resistance. Publications were inconsistent prior to 2017, but steadily increased after 2017. China generated the most papers and the United States of America received the most citations and the highest H-index. Baylor College of Medicine was the most influential institution in this field, with the highest number of publications and citations, as well as the highest H-index. Helicobacter was the most productive journal, followed by the World Journal of Gastroenterology and Frontiers in Microbiology. The World Journal of Gastroenterology had the highest citation. Graham, David Y was the most productive and cited author. Clarithromycin resistance, prevalence, gastric cancer, quadruple therapy, sequential therapy, 23S rRNA, whole genome sequencing, bismuth, and probiotics appeared with a high frequency in the keywords. The top keywords with the highest citation bursts were vonoprazan, RdxA, biofilm formation, and fatty acid chain. Our research illustrated a multi-dimensional facet and a holistic knowledge structure for H. pylori antibiotic resistance research over the past decade, which can serve as a guide for the H. pylori research community to conduct in-depth investigations in the future.

Combating antimicrobial resistance (AMR) is among the 10 global health issues identified by the World Health Organization (WHO) in 2021. While AMR is a naturally occurring process, the inappropriate use of antibiotics in different settings and legislative gaps has led to its rapid progression. As a result, AMR has grown into a serious global menace that impacts not only humans but also animals and, ultimately, the entire environment. Thus, effective prophylactic measures, as well as more potent and non-toxic antimicrobial agents, are pressingly needed. The antimicrobial activity of essential oils (EOs) is supported by consistent research in the field. Although EOs have been used for centuries, they are newcomers when it comes to managing infections in clinical settings; it is mainly because methodological settings are largely non-overlapping and there are insufficient data regarding EOs' in vivo activity and toxicity. This review considers the concept of AMR and its main determinants, the modality by which the issue has been globally addressed and the potential of EOs as alternative or auxiliary therapy. The focus is shifted towards the pathogenesis, mechanism of resistance and activity of several EOs against the six high priority pathogens listed by WHO in 2017, for which new therapeutic solutions are pressingly required.

Although discovered 40 years ago, Helicobacter pylori infection is still raising diagnostic and therapeutic problems today. The infection is currently managed based on statements in several guidelines, but implementing them in practice is a long process. Increasing antibiotic resistance and weak compliance of the patients limit the efficacy of eradication regimens, leaving much room for improvement. Third-generation proton pump inhibitors have added little to the results of the first two generations. Potassium-competitive acid blockers have a stronger and longer inhibitory action of acid secretion, increasing the intragastric pH. They obtained superior results in eradication when compared to proton pump inhibitors. Instead of innovative antibiotics, derivatives of existing antimicrobials were developed; some new fluoroquinolones and nitazoxanide seem promising in practice, but they are not recommended by the guidelines. Carbonic anhydrase inhibitors have both anti-secretory and bactericidal effects, and some researchers are expecting their revival in the treatment of infection. Capsules containing components of the eradication regimens have obtained excellent results, but are of limited availability. Probiotics, if containing bacteria with anti-Helicobacter pylori activity, may be useful, increasing the rates of eradication and lowering the prevalence and severity of the side effects.

Purpose: Vonoprazan (VPZ) produces a strong acid-inhibitory effect, which can potentially eradicate Helicobacter Pylori (H. pylori). We aimed to assess whether a 14-day VPZ-containing triple therapy was safe and effective in the Chinese population and the potential mechanism. Methods: Enrolled patients confirmed to be infected with H. pylori were randomly divided into four groups: VPZ + doxycycline + furazolidone, VPZ + doxycycline + amoxicillin, esomeprazole (EPZ) + bismuth + doxycycline + furazolidone, and EPZ + colloidal bismuth + doxycycline + amoxicillin for 14 days. The eradication rate, medication adherence, and incidence of adverse events (AEs) were evaluated. Inhibition of H. pylori by VPZ and EPZ in vitro was assessed. H. pylori treated with appropriate concentrations of VPZ and EPZ were sequenced by transcriptome analysis to explore the antibacterial mechanism. Results: A higher eradication rate were observed in VPZ-containing triple therapy. No obvious differences were observed in medication adherence or the incidence of AEs. VPZ had no direct inhibitory effect on H. pylori, whereas EPZ directly inhibited H. pylori may through downregulated genes related to the ribosome. Conclusion: In the Chinese population, 14-day VPZ-containing triple therapy was safe and more effective and can be used clinically as first-line H. pylori treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05097846.

Helicobacter pylori infects a large percentage of the world's population and is etiologically related to gastric cancer. The U.S. Food and Drug Administration recently approved two 14-day vonoprazan-containing regimens (vonoprazan-amoxicillin with or without clarithromycin) for H. pylori infections in the United States/Europe.

We critically reviewed the trial methods to discover why the results were unacceptable low [i.e., no regimen achieved clinically acceptable (≥ 90%) or even conditionally acceptable cure rates (≥ 85%)]. Cure rates with antibiotic susceptible strains were 84.7 for vonoprazan triple therapy, 78.5 for vonoprazan-amoxicillin, and 78.7 for lansoprazole triple therapy, respectively. As was previously shown in Japan, the benefit from adding clarithromycin to vonoprazan-amoxicillin was minimal and the majority of the clarithromycin administered was unnecessary.

The possible reasons for failure to achieve high cure rates discussed include (a) reduced intragastric antibiotic concentrations, (b) an increase in heteroresistance, and (c) failure to achieve an intragastric pH conducive for amoxicillin to eradicate the infection. In addition, there was no pilot study or other attempt to optimize any regimen.

The most likely reason for failure was failure to achieve high intragastric concentrations of antibiotics or to achieve an intragastric pH conducive for amoxicillin to be active. Importantly, vonoprazan triple therapy resulted in > 10 tons of unneeded clarithromycin/million courses of vonoprazan triple therapy. Antibiotic misuse combined with low cure rates suggest that vonoprazan-clarithromycin triple therapies should not be prescribed for H. pylori infection. Dual vonoprazan-amoxicillin therapy has proven effective elsewhere and after optimization may eventually prove useful in the U.S./Europe.

Current recommendations on Helicobacter pylori (H. pylori) eradication in children differ from adults. In H. pylori-infected adults, the eradication is always recommended because of the risk to develop gastrointestinal and non-gastrointestinal associated diseases. Instead, before treating infected children, we should consider all the possible causes and not merely focus on H. pylori infection. Indeed, pediatric international guidelines do not recommend the test and treat strategy in children. Therefore, gastroscopy with antimicrobial susceptibility testing by culture on gastric biopsies should be performed before starting the eradication therapy in children to better evaluate all the possible causes of the symptomatology and to increase the eradication rate. Whether antibiotic susceptibility testing is not available, gastroscopy is anyway recommended to better set any possible cause of symptoms and not simply focus on the presence of H. pylori. In children the lower antibiotics availability compared to adults forces to treat based on antimicrobial susceptibility testing to minimize the unsuccessful rates. The main antibiotics used in children are amoxicillin, clarithromycin, and metronidazole in various combinations. In empirical treatment, triple therapy for 14 days based either on local antimicrobial susceptibility or on personal antibiotic history is generally recommended. Triple therapy with high dose of amoxicillin is a valid alternative choice, either in double resistance or in second-line treatment. Moving from therapeutic regimens used in adults, we could also select quadruple therapy with or without bismuth salts. However, all the treatment regimens often entail unpleasant side effects and lower compliance in children. In this review, the alternative and not yet commonly used therapeutic choices in children were also analyzed.

The eradication of Helicobacter pylori (H. pylori) infection remains challenging due to increasing bacterial resistance. Resistance rates to clarithromycin, metronidazole, and levofloxacin were higher than 30% in the USA, making current therapies less effective. Vonoprazan triple therapy (VAC) has demonstrated similar efficacy and safety profiles compared to PPI-based triple therapy (PPI). However, the eradication rate of vonoprazan dual therapy (VA) for H. pylori infection in comparison to VAC, and PPI was poorly established. Electronic databases were searched up to 6 October 2022, to identify studies examining the safety and efficacy of VA compared to VAC and PPI. Six studies were included. For empiric therapies among treatment naïve patients, VA, VAC, and PPI did not achieve high cure rates (>90%). The comparative efficacy ranking showed VAC was the most effective therapy, followed by VA, and PPI. The results were similar for clarithromycin-resistant infections. The comparative safety ranking showed VA ranked first, whereas PPI triple therapy was the least safe regimen. These findings should guide the selection of the most effective and safe treatment and conduct additional studies to determine the place of vonoprazan dual versus triple therapies in patients with H. pylori from various countries across the world.

Although vonoprazan has been proven to be a highly potent drug for Helicobacter pylori eradication, there have been no randomized trials comparing the effectiveness of regimens containing vonoprazan 20 mg daily with alternative standard strategies. We aimed to assess the efficacy, tolerance, and cost-effectiveness of quadruple therapy with vonoprazan 20 mg daily as a first-line therapy for H. pylori eradication.

We conducted a single-center, open-label, noninferiority, randomized controlled study in Zhejiang, China. Treatment-naive H. pylori-positive participants (n = 234) were randomly assigned to three groups in a 1:1:1 ratio: vonoprazan 20 mg daily with amoxicillin 1000 mg, furazolidone 100 mg and colloidal bismuth 200 mg each given twice a day for 10 days (V10) or 14 days (V14), or esomeprazole 20 mg with amoxicillin 1000 mg, furazolidone 100 mg and colloidal bismuth 200 mg each given twice a day for 14 days (E14). The primary endpoint was the eradication rates in each group. The secondary endpoints were the incidence of adverse events (AEs) and compliance.

The eradication rates in the V10, V14 and E14 groups were 96.2% (89.2-99.2%), 94.9% (87.4-98.6%), and 93.6% (85.7-97.9%) in the intention-to-treat analysis, and 98.6% (92.7-100.0%), 97.4% (90.8-99.7%), and 94.8% (87.2-98.6%) in the per-protocol analysis, respectively. Quadruple therapy with vonoprazan 20 mg daily was noninferior to the esomeprazole-based regimen (Farrington and Manning test: margin 10%, significance level 2.5%). The adverse event rates were 12.8% versus 3.8% versus 6.4% in the V10, V14, and E14 groups, respectively. All regimens were well tolerated without significant differences (p = 0.096). The cost-effectiveness ratio was 1.32, 1.88, and 3.06 for the V10, V14, and E14 groups in the intention-to-treat analysis, respectively. (NCT04907747).

Vonoprazan (20 mg daily) was as effective as esomeprazole (20 mg twice a day) in quadruple therapies for the eradication of H. pylori, was more economical, and was well tolerated. In addition, the 10-day regimen of vonoprazan (20 mg daily) was comparable to the 14-day regimen.

Due to increasing antibiotic resistance, various Helicobacter pylori eradication regimens other than clarithromycin-based therapies have been proposed. However, detailed data on which therapies were employed and their eradication success is lacking. The purpose of this study was to analyse the response rates of different eradication therapy schemes.

In this retrospective cohort study, we analysed data of 1721 patients and included 608 patients undergoing H. pylori eradication therapy at the Department of Gastroenterology at the University Hospital Zurich between 2004 and 2018. The primary endpoint was the success rates of clarithromycin- and non-clarithromycin-containing H. pylori eradication regimens. We furthermore analysed factors with potential impact on the outcome of H. pylori eradication therapies, such as demographics, and smoking and social status.

The most common therapy scheme (71% of all cases) was proton pump inhibitor (PPI)-amoxicillin-metronidazole, followed by PPI-amoxicillin-clarithromycin (21%) and PPI-metronidazole-clarithromycin (6%). There was no difference between the H. pylori eradication success of clarithromycin vs non-clarithromycin-containing therapies (71% vs 71%, p = 0.764).

Despite increasing clarithromycin resistance globally, there was no difference in the eradication success of clarithromycin- and non-clarithromycin-containing therapy regimens in Switzerland. As varying triple therapies do not increase eradication rates in real-world settings, other primary therapy options such as quadruple therapies should be explored.

As a first-line treatment regimen for Helicobacter pylori (H. pylori) infection, antibiotic therapy is widely used worldwide. However, the question of increasing antibiotic resistance must be considered. Given this issue, we need to find ways to reduce drug resistance. This study examined all currently available first-line regimens and compared them with standard triple treatment through a network meta-analysis of randomized controlled trials (RCTs).

To compare first-line treatment regimens for eradication of antibiotic-resistant H. pylori strains.

To compare the effectiveness of the first-line regimens for treating H. pylori infection, a Bayesian network meta-analysis was applied to process data extracted from RCTs. The plausible ranking for each regimen was assessed by the surface under the cumulative ranking curve (SUCRA). In addition, we conducted a relevant search by reference citation analysis.

Twenty-five RCTs involving 12029 participants [including 1602 infected with clarithromycin (CAM)-resistant strains and 1716 infected with metronidazole (MNZ)-resistant strains] were included, in which a total of seven regimens were used for H. pylori eradication. The results showed that dual therapy containing a high-dose proton pump inhibitor (HDDT) [odds ratio (OR): 4.20, 95% confidence interval (CI): 2.29-8.13] was superior to other therapies for all patients, including those with CAM/MNZ-resistant H. pylori infection. In the comparative effectiveness ranking, for CAM-resistant H. pylori, HDDT (OR: 96.80, 95%CI: 22.46-521.9) had the best results, whereas standard triple therapy ranked last (SUCRA: 98.7% vs 0.3%). In the subgroup of high cure rates (≥ 90%), HDDT was also generally better than other therapies.

For the eradication of CAM- and MNZ-resistant H. pylori strains, HDDT exhibited considerable advantages. The studies of CAM-resistant H. pylori were based on small samples due to a lack of antibiotic sensitivity tests in many RCTs, but the results showed that all patients, including those with CAM-resistant H. pylori infection, had a concordant trend. Overall, HDDT may be a reference for RCTs and other studies of H. pylori eradication.

The efficacy and safety of amoxicillin-vonoprazan (VA) dual therapy remained unclear.

This systematic review was conducted in accordance with the PRISMA 2009 guidelines. A systematic search of the Pubmed, Embase, and Cochrane database was conducted using the combination of "Helicobacter pylori or H. pylori or Hp," "amoxicillin or penicillin," and "Vonoprazan or TAK-438 or Takecab or (potassium AND competitive) or potassium-competitive." The initial and secondary outcome of this meta-analysis was to evaluate the efficacy and safety of VA dual therapy.

Three studies and 668 H. pylori infected patients were included in this meta-analysis. The crude eradication rate of VA dual therapy was 87.5% and 89.6% by ITT and PP analysis, respectively. No significant differences were observed regarding the VA dual therapy and vonoprazan-amoxicillin-clarithromycin (VAC) triple therapy according to ITT (RR = 0.99, 95% CI, 0.93-1.05, P = 0.65) and PP (RR = 0.99, 95% CI, 0.94-1.05, P = 0.82) analysis. The side effect of VA dual therapy was 19.1% (95% CI, 5.9-32.4), which was lower than that of VAC triple therapy but there was no statistical significance (RR = 0.75, 95% CI, 0.59-1.06, P = 0.12).

VA dual therapy shows acceptable efficacy, good safety and avoid unnecessary antibiotic use in the first-line treatment for H. pylori infection. However, its application in other regions need to be further explored.

Novel, effective treatments for Helicobacter pylori infection are needed. This study evaluated the efficacy of vonoprazan, a potassium-competitive acid blocker, vs standard treatment on H pylori eradication in the United States and Europe.

In a randomized, controlled, phase 3 trial, treatment-naïve adults with H pylori infection were randomized 1:1:1 to open-label vonoprazan dual therapy (20 mg vonoprazan twice daily; 1 g amoxicillin 3 times daily), or double-blind triple therapy twice a day (vonoprazan 20 mg or lansoprazole 30 mg; amoxicillin 1 g; clarithromycin 500 mg) for 14 days. The primary outcome was noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains (noninferiority margin = 10%). Secondary outcomes assessed superiority in eradication rates in clarithromycin-resistant infections, and in all patients.

A total of 1046 patients were randomized. Primary outcome eradication rates (nonresistant strains): vonoprazan triple therapy 84.7%, dual therapy 78.5%, vs lansoprazole triple therapy 78.8% (both noninferior; difference 5.9%; 95% confidence interval [CI], -0.8 to 12.6; P < .001; difference -0.3%; 95% CI, -7.4 to 6.8; P = .007, respectively). Eradication rates in clarithromycin-resistant infections: vonoprazan triple therapy 65.8%, dual therapy 69.6%, vs lansoprazole triple therapy 31.9% (both superior; difference 33.9%; 95% CI, 17.7-48.1; P < .001; difference 37.7%; 95% CI, 20.5-52.6; P < .001, respectively). In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, vs 68.5%, difference 12.3%; 95% CI, 5.7-18.8; P < .001; difference 8.7%; 95% CI, 1.9-15.4; P = .013). Overall frequency of treatment-emergent adverse events was similar between vonoprazan and lansoprazole regimens (P > .05).

Both vonoprazan-based regimens were superior to proton pump inhibitor-based triple therapy in clarithromycin-resistant strains and in the overall study population.

gov; NCT04167670.

H. pylori eradication reduces the risk of gastric malignancies and peptic ulcer disease. First-line therapies include 14-day PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) and PBMT (PPI, bismuth, metronidazole, tetracycline). Second-line therapies include 14-day PBMT and PAL (PPI, amoxicillin, levofloxacin). This clinical audit examined current treatment outcomes in Singapore.

Clinical data of H. pylori-positive patientswho underwent empirical first- and second-line eradication therapies from 1 January 2017 to 31 December 2018 were reviewed. Treatment success was determined by 13C urea breath test performed at least 4 weeks after treatment and 2 weeks off PPI.

A total of 963 patients (862 PAC, 36 PMC [PPI, metronidazole, clarithromycin], 18 PBMT, 13 PBAC [PAC with bismuth], 34 others) and 98 patients (62 PMBT, 15 PAL, 21 others) received first-and second-line therapies respectively. A 14-day treatment duration was appropriately prescribed for first- and second-line therapies in 65.2% and 82.7% of patients, respectively. First-line treatment success rates were noted for PAC (seven-day: 76.9%, ten-day: 88.3%, 14-day: 92.0%), PMC (seven-day: 0, ten-day: 75.0%, 14-day: 69.8%), PBMT (ten-day: 100%, 14-day: 87.5%) and PBAC (14-day: 100%). 14-day treatment was superior to seven-day treatment (90.8% vs. 71.4%; P = 0.028). PAC was superior to PMC (P < 0.001) but similar to PBMT (P = 0.518) and PBAC (P = 0.288) in 14-day therapies. 14-day second-line PAL and PBMT had similar efficacy (90.9% vs. 82.4%; P = 0.674).

First-line empirical treatment using PAC, PBMT and PBAC for 14 days had similar efficacy. Success rates for second-line PBMT and PAL were similar.

One-week triple therapy with vonoprazan is endorsed by Japanese guidelines as an alternative to proton pump inhibitor (PPI)-based triple therapy for first-line Helicobacter pylori eradication. This contrasts with Western guidelines recommending 2-week PPI-based triple therapy.

To verify the non-inferiority of 1-week vonoprazan-based triple therapy versus 2-week PPI-based triple therapy as first-line H. pylori eradication in a multiracial Asian cohort.

Randomised controlled trial of treatment-naïve patients with H. pylori infection assigned 1:1 to either 7 days amoxicillin 1 g + clarithromycin 500 mg + vonoprazan 20 mg twice per day or 14 days amoxicillin 1 g + clarithromycin 500 mg + omeprazole OR esomeprazole OR rabeprazole 20 mg twice/day. Subjects were randomly assigned to each PPI 1:1:1 Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between groups.

Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. 244 (age [SD] 51.7 [14.6]) received vonoprazan- (n = 119) or PPI-based (n = 125) triple therapy. Eradication rates by intention-to-treat analysis were 87.4% (vonoprazan-based triple therapy) versus 88.0% (PPI-based triple therapy. By per protocol analysis: 96.3% (vonoprazan-based triple therapy) versus 94.0% (PPI-based triple therapy). Clarithromycin resistance predicted treatment failure on multivariate analysis: RR 11.4; 95% CI [1.4-96.3], p = 0.025. No significant differences in CYP 2C19 genotypes or adverse events occurred between groups.

One-week vonoprazan-based triple therapy achieved comparable efficacy to 2-week PPI-based triple therapy and was well tolerated.

Potassium-Competitive Acid Blockers (P-CABs) have been used in Helicobacter pylori (H. pylori) eradication therapies in recent years. However, the efficacy and safety of P-CABs compared to Proton-Pump Inhibitors (PPIs) in this setting remain controversial.

The efficacy and safety of P-CABs and PPIs for H. pylori eradication were compared in a meta-analysis based on a systematic literature search of major electronic databases for relevant Randomized Controlled Trials (RCTs).

Seven studies and 1,168 patients were included. The pooled eradication rate determined by Intention-To-Treat (ITT) analysis was 90.2% for P-CAB-based and 75.5% for PPI-based triple therapy (pooled RR [95% CI] = 1.17 [1.08-1.28], p < 0.001). The Per-Protocol (PP) analysis also demonstrated significant superiority of P-CABs (pooled eradication rate = 92.4% vs. 77.8%; pooled RR [95% CI] = 1.14 [1.03-1.26], p < 0.01). In a subgroup evaluation, P-CABs were significantly better than PPIs as a first-line eradication therapy, in both the ITT analysis (pooled eradication rate = 91.8% vs. 76.4%; pooled RR [95% CI] = 1.18 [1.10-1.28], p < 0.0001) and the PP analysis (pooled eradication rate = 93.0% vs. 78.6%; pooled RR [95% CI] = 1.13 [1.02-1.26], p < 0.05). However, P-CABs were not superior to PPIs when administered as salvage therapy, as determined in the ITT (75.0% vs. 66.0%, pooled RR [95% CI] = 1.11 [0.69-1.78], p = 0.66) and PP (85.7% vs. 70.0%, pooled RR [95% CI] = 1.20 [0.82-1.75], p = 0.34) analyses. In a subgroup analysis limited to Japanese patients, both the ITT analysis (pooled eradication rate = 89.6% vs. 73.9%; RR [95% CI] = 1.21 [1.14-1.29], p < 0.01) and the PP analysis (pooled eradication rate = 92.0% vs. 75.7%; RR [95% CI] = 1.18 [1.06-1.32], p < 0.01) showed that P-CABs were significantly superior compared to PPIs as triple eradication therapy. However, in the subgroup analysis of patients from other countries, there was no significant difference in either the ITT analysis (pooled eradication rate = 93.8% vs. 85.2%; RR [95% CI] = 1.10 [0.99-1.22], p = 0.07) or PP analysis (pooled eradication rate = 95.0% vs. 90.8%; RR [95% CI] = 1.05 [0.98-1.14], p = 0.17). The incidence of adverse events associated with the two regimens did not significantly differ (P-CABs vs. PPIs: 33.6% vs. 40.0%; RR [95% CI] = 0.84 [0.71‒1.00], p = 0.05). The incidence of serious adverse events and dropout rate due to adverse events also did not differ (p = 0.44 and p = 0.67, respectively).

The efficacy of P-CAB-based triple therapy is superior to that of PPI-based triple therapy as a first-line approach to H. pylori eradication, particularly in Japanese patients. As salvage therapy, the efficacy of the two treatments did not significantly differ. The tolerability of P-CAB-based and PPI-based triple therapy was comparable, as was the incidence of adverse events.

Duodenal ulcers, especially caused by increasingly drug-resistant Helicobacter pylori, are a concern in Asia. We compared oral vonoprazan versus lansoprazole for efficacy (healing duodenal ulcers) and safety in non-Japanese Asian patients.

In this phase 3, randomized (1:1), double-blind, double-dummy, parallel-group, non-inferiority study (April 5, 2017, to July 19, 2019), patients with ≥ 1 endoscopically confirmed duodenal ulcer, at 52 hospitals (China, South Korea, and Taiwan), received vonoprazan 20 mg once daily (QD) or lansoprazole 30 mg QD for 6 weeks maximum. Patients with H. pylori received bismuth-containing quadruple therapy including vonoprazan 20 mg twice daily (BID) or lansoprazole 30 mg BID, for 2 weeks, followed by vonoprazan or lansoprazole monotherapy QD (4 weeks maximum). Endpoints were endoscopically confirmed duodenal ulcer healing (Week 4/6; primary) and H. pylori eradication (4 weeks post-treatment; secondary); non-inferiority margins were -6% and -10%, using a two-sided 95% confidence interval (CI).

Of 533 enrolled patients, one was lost to follow-up and one withdrew (full analysis set: 531 patients [vonoprazan, n = 263; lansoprazole, n = 268]; 85.4% = H. pylori positive). Vonoprazan was non-inferior to lansoprazole for duodenal ulcer healing (96.9% vs 96.5%; difference 0.4% [95% CI -3.00, 3.79]). H. pylori eradication rates were 91.5% (vonoprazan) and 86.8% (lansoprazole; difference 4.7% [95% CI -1.28, 10.69]). Vonoprazan and lansoprazole were well tolerated, with similar safety profiles, no new safety signals; no deaths occurred.

Vonoprazan was well tolerated and non-inferior to lansoprazole for duodenal ulcer healing and achieved H. pylori eradication above the clinically meaningful threshold (90%), in non-Japanese Asian patients.

Patients with acid-related disorders (ARDs) of the upper digestive tract remain highly prevalent and need to be continuously investigated to improve their management.

This review provides a summary of the most recent advancements in the treatment of ARDs with particular focus on the new drugs available to overcome the unmet needs of traditional therapies.

Proton pump inhibitors remain the best therapy in treating ARDs, but a consistent proportion of these patients continues to present mucosal lesions or to experience symptoms despite treatment. These cases pertain mainly to the most severe forms of erosive esophagitis or to non-erosive reflux disease. Also, the increasing rate of patients with H. pylori infection not responding to eradication therapy represents a difficult clinical condition. The recent advent of a new class of antisecretory drugs, such as the potassium competitive acid blockers and, among them the most studied vonoprazan, which are characterized by a better pharmacological profile than PPIs (rapid onset of action, longer lasting acid suppression, control of nocturnal acidity), has the potential to overcome the above-mentioned unmet needs. More research should be done to assess their efficacy in Western populations and their safety in patients treated in the long term.

Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.

The Helicobacter pylori (H. pylori) eradication rate of proton pump inhibitor (PPI)-based regimen remains decreasing. Vonoprazan (VPZ), a stronger and longer-lasting acid blocker, has been proposed to treatment of H. pylori infection. However, previous reviews did not have a pre-established study protocol and did not conduct a comprehensive search of the database, so the results obtained were not robust. We aimed to perform a meta-analysis to assess the effectiveness and safety of VPZ-based regimens for treatment of H. pylori infection in comparison with other regimens.

We conducted a systematic literature search on PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials and ChiCTR Register. Randomized clinical trials comparing VPZ-based regimens with similar eradication regimens without VPZ in the treatment of H. pylori infection were included. Eradication rate, compliance of the patients and side effects were specified as the primary outcomes. RevMan 5.4 software was used to analyze the RCTs and provide pooled risk ratio (RR) with 95% confidence intervals (CI). Systematic searches, study selection, data extraction, risk of bias assessment and statistical analysis were performed by two independent researchers according to the predesigned criteria on the PROSPERO.

A total of 8 RCTs with 2012 patients qualified for evaluation. The results showed that the eradication rate of VPZ-containing regimens was significantly superior to PPI-containing regimens for both intention-to-treat (RR, 1.14; 95% CI: 1.06-1.23; p = 0.0006) and per-protocol analyses (RR, 1.12; 95% CI: 1.04-1.20; p = 0.003). Subgroup analysis based on treatment regimens, eradication experience and clarithromycin resistance, as well as sensitivity analysis further confirmed this finding. In addition, there was no significant difference in compliance (RR, 1.02; 95% CI: 0.98-0.1.05; p = 0.35) and the frequency of adverse events (RR, 0.84; 95% CI: 0.70-1.00; p = 0.05) between the regimens.

Compared with PPI-based regimens, the VPZ-containing regimens showed a comparable or even superior eradication rate of H. pylori in terms of overall comparison and comparison of different treatment regimens, eradication experience and clarithromycin resistance. In addition, VPZ-based regimens have better tolerability and fewer adverse events. More future studies are needed to evaluate the impact of some differences in patient characteristics.

PROSPERO CRD42021229598.