Vonoprazan Research Articles

Chromatographic assay of recently approved co-formulation of Vonoprazan fumarate with low dose Aspirin: AGREE, Complex MoGAPI, and RGB 12-model assessments.

Two simple, valid and green chromatographic based techniques are developed in the present work for first time to simultaneously analyze the recently approved combination of Aspirin (ASP) with the novel gastro-protective agent Vonoprazan (VON). First method is an HPLC-DAD "diode array detection", where separation was successful using C18 (250 × 4.6mm) column with isocratic elution of phosphate buffer-pH 6.8 and acetonitrile in ratio of 63:37 with detection at 230nm. Second method is an HPTLC method on HPTLC silica plates using ethyl acetate: ethanol (75%): ammonia (5:5:0.05 v/v) mobile phase followed by densitometric scanning at 230nm. The methods were applied successfully for analysis of VON and ASP mixture in laboratory-prepared tablets and the methods were validated in regards to linearity, precision, accuracy and selectivity. The proposed methods are assessed for their greenness and whiteness as well using the "Analytical GREEnness Metric Approach", "Complementary Modified Green Analytical Procedure Index" and the new algorithm "RGB 12 model" (Red-Green-Blue) and proved the greenness and the sustainability of the methods in the routine assay of the newly marketed formulation.

Efficacy and safety of vonoprazan-based bismuth quadruple therapy for first-line Helicobacter pylori eradication: A large-scale, real-world study.

Vonoprazan (VPZ) has been shown to have superior acid-inhibitory effects compared to proton pump inhibitors (PPIs). However, there is a paucity of research examining the efficacy of vonoprazan-based bismuth quadruple therapy (VBQT) in the eradication of primary Helicobacter pylori infection. This study aimed to evaluate the effectiveness and safety of VBQT as a first-line treatment for H pylori eradication. This retrospective, real-world, single-arm study included consecutive treatment-naive patients who received VBQT (VPZ 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, bismuth potassium citrate 220 mg, all administered twice daily for 14 days) for H pylori eradication between March 1, 2021, and May 30, 2023. The study included both outpatients and inpatients. Eradication rates were assessed using 13C-urea breath tests or 14C-urea breath tests performed 4 to 6 weeks after treatment. The primary outcomes included eradication rates, adverse events, and treatment compliance. A total of 612 H pylori-infected patients were included in the study. The intention-to-treat (ITT), modified ITT (MITT), and per-protocol analyses showed H pylori eradication rates of 84.3% (95% CI: 812% to 87.1%), 95.9% (95% CI: 93.9% to 97.4%), and 96.4% (95% CI: 94.4% to 97.8%), respectively. In the ITT analysis, the adverse event rate was 12.7%, and the treatment compliance rate was 96.9%. In real-world practice, the VBQT regimen demonstrates excellent efficacy and favorable tolerability as a first-line therapy for H pylori eradication.

Study on the clinical efficacy of 14-day vonoprazan-based triple regimen in obese patients with Helicobacter pylori infection

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.

Efficacy and safety of Vonoprazan-based treatment of Helicobacter pylori infection: a systematic review and network meta-analysis

ObjectiveThe 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.DesignThrough 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.ResultsThe 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.ConclusionCompared 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.

Factorial design-aided derivatization-free fluorimetric ultrasensitive assay of vonoprazan with application in uniformity of dosage units and plasma samples analysis: Comprehensive and comparative greenness and whiteness assessment

This study presents a novel derivatization-free spectrofluorimetric method for the quantification of vonoprazan (VPZ) that is characterized by its high sensitivity, environmental friendliness, and cost-effectiveness. Notably, this method eliminates the requirement for pre-derivatization, extraction procedures, large amounts of organic solvents, and/or expensive instrumentation, which distinguishes it from previous approaches. The approach employed in this study relies on the formation of an association complex between VPZand the xanthene dye acid red 87 (AR87) under acidic conditions. The stability of the VPZ-AR87 complex was determined to be remarkably high, with a complex formation constant (Kf) value exceeding 2 x 106 M−1. The fluorimetric measurements rely on the quantitative and selective quenchingof the dye’s native fluorescence emission at 545 nm. The experimental parameters were optimized utilizing a quality-by-design 23 full factorial design. This strategy yielded a highly favorable linearity range of 10.0 to 400.0 ng/mL, with a correlation coefficient (r) of 0.9997. The presented methodology exhibited a high level of sensitivity, as evidenced by its ability to detect concentrations as low as 1.2 ng/mL. This sensitivity enabled its successful application for the estimation of VPZ in human plasma samples with high %recoveries (98.21–101.67) and low %RSD values (<1.52). Furthermore, content uniformity testing of low-dose VPZ tablets was performed according to United States Pharmacopeia guidelines. Greenness and whiteness metrics analysis showed a significant advantage of the proposed method over previously reported fluorimetric methods. Validation of the developed approach was carried out in accordance with ICHQ2 (R1) guidelines.

Comparison of vonoprazan bismuth-containing triple therapy with quadruple therapy in Helicobacter pylori-infected treatment-naive patients: a prospective multicenter randomized controlled trial.

Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4weeks after treatment completion. Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P<0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P<0.001). Triple therapy comprising vonoprazan (20mg), amoxicillin (750mg), and bismuth potassium citrate (220mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

Single-Arm, Prospective, Interventional Study of Helicobacter pylori Eradication Rescue Therapy with Rifabutin, Metronidazole, and Vonoprazan.

Background and Objective: Rescue Helicobacter pylori eradication can be challenging. Rifabutin (RBT) demonstrates high activity against Helicobacter pylori and is incorporated into various rescue eradication regimens. This exploratory study was performed to evaluate the efficacy and safety of a rescue regimen comprising RBT, metronidazole (MNZ), and vonoprazan (VPZ). Methods: This prospective, single-center, single-arm, interventional study was performed in Japan. Eligible patients were those who underwent failed primary eradication treatment (7-day treatment with three drugs: VPZ or a proton pump inhibitor [PPI], amoxicillin [AMPC], and clarithromycin) and secondary eradication treatment (7-day treatment with three drugs: VPZ or a PPI, AMPC, and MNZ) and those who were unable to receive first- and second-line therapy because of penicillin allergy. Twenty Helicobacter pylori-positive patients were treated with RBT (150 mg twice daily), MNZ (250 mg twice daily), and VPZ (20 mg twice daily) for 10 days (RBT-MNZ-VPZ therapy). Eradication success was evaluated using the urea breath test. Drug susceptibility test results were available in 16 patients. This study is registered in the Japan Registry of Clinical Trials (jRCT031220504). Results: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of RBT-MNZ-VPZ therapy were 70% (90% confidence interval [CI]: 49.2%-86.0%) and 72.2% (95% CI: 50.2%-88.4%), respectively. In the MNZ-susceptible subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were 100% (90% CI: 68.8%-100%) and 100% (90% CI: 65.2%-100%). In the MNZ-resistant subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were both 62.5% (90% CI: 28.9%-88.9%). All infections were RBT-susceptible. Conclusions: These findings suggest that RBT-MNZ-VPZ therapy may be a promising rescue regimen, especially in MNZ- and RBT-susceptible infections or patients with penicillin allergy.

Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

Advanced interpenetrating polymer networks for innovative gastroretentive formulations targeting Helicobacter pylori gastric colonization

The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.

Efficacy of Vonoprazan vs. Intravenous Proton Pump Inhibitor in Prevention of Re-Bleeding of High-Risk Peptic Ulcers: A Randomized Controlled Pilot Study.

Background: Proton pump inhibitor (PPI) therapy is well-established for its effectiveness in reducing re-bleeding in high-risk peptic ulcer patients following endoscopic hemostasis. Vonoprazan (VPZ) has demonstrated the capacity to achieve gastric pH levels exceeding 4, comparable to PPIs. This study aims to evaluate the comparative efficacy of intravenous PPI infusion versus VPZ in preventing re-bleeding after endoscopic hemostasis in patients with high-risk peptic ulcers. Methods: A randomized, double-blind, controlled, and double-dummy design was employed. Patients with peptic ulcer bleeding (Forrest class IA/IB or IIA/IIB) who underwent endoscopic hemostasis were randomly assigned to either the PPI group or the VPZ group. Re-bleeding rates at 3, 7, and 30 days, the number of blood transfusions required, length of hospitalization, and ulcer healing rate at 56 days were assessed. Results: A total of 44 eligible patients were enrolled, including 20 patients (PPI group, n = 11; VPZ group, n = 9) with high-risk peptic ulcers. The mean age was 66 years, with 70% being male. Re-bleeding within 72 h occurred in 9.1% of the PPI group versus 0% in the VPZ group (p = 1.000). There was no significant difference in re-bleeding rates within 7 days and 30 days (18.2% vs. 11.1%, p = 1.000). Additionally, the ulcer healing rate did not significantly differ between the groups (87.5% vs. 77.8%). Conclusions: This pilot study demonstrates comparable efficacy between oral vonoprazan and continuous PPI infusion in preventing recurrent bleeding events among high-risk peptic ulcer patients following successful endoscopic hemostasis.

Evaluating vonoprazan and tegoprazan for gastroesophageal reflux disease treatment in Chinese Healthcare: an EVIDEM framework analysis

BackgroundIn Chinese healthcare settings, drug selection decisions are predominantly influenced by the Pharmacy & Therapeutics Committee (PTC). This study evaluates two recently introduced potassium-competitive acid blockers, vonoprazan (VPZ) and tegoprazan (TPZ), utilizing the Evidence and Value: Impact on DEcisionMaking (EVIDEM) framework.MethodsThe study employed the 10th edition of EVIDEM, which includes a core model with five domains and 13 criteria. Two independent expert panels were involved: the PTC expert panel, tasked with assigning weights using a 5-point scale, defining scoring indicators, examining the evidence matrix, scoring, and decision-making; and the evidence matrix expert panel, responsible for conducting a systematic literature review, creating the evidence matrix, and evaluating the value contributions of VPZ and TPZ.ResultsThe analysis estimated the value contributions of VPZ and TPZ to be 0.59 and 0.54, respectively. The domain of ‘economic consequences of intervention’ showed the most significant variation in value contribution between the two drugs, followed by ‘comparative outcomes of intervention’ and ‘type of benefit of intervention’.ConclusionEmploying the EVIDEM framework, VPZ’s value contribution was found to be marginally superior to that of TPZ. The EVIDEM framework demonstrates potential for broader application in Chinese medical institutions.

An eco-friendly liquid chromatographic analysis of the triple therapy protocol of amoxicillin, metronidazole and vonoprazan for H. Pylori eradication: application to combined dosage forms and simulated gastric fluid

Helicobacter pylori has a big sway when peptic ulcers are concerned. For its eradication, different protocols have been approved. Among which, the tripartite therapy protocol which embraces vonoprazan as potassium competitive acid blocker in combination with amoxicillin and metronidazole as antibiotics. An environmentally benign HPLC method is addressed in order to simultaneously determine amoxicillin (AMX), metronidazole (MET) and vonoprazan (VPZ) in bulk powder and combined tablet mixture. Full separation of AMX, MET and VPZ is accomplished using C8 column, and a gradient mobile phase system, composed of methanol and phosphate buffer of a pH value of 5. Fine linearity in the concentration ranges 50–600 µg mL−1 amoxicillin, 50–400 µg mL−1 metronidazole and 10–100 µg mL−1 vonoprazan was denoted by the high correlation coefficient (0.9999). The method accuracy and precision are confirmed upon analyzing AMX, MET and VPZ triple therapy not only in their synthetic mixtures and combined tablet mixtures but also in their combined tablet mixtures in simulated gastric fluid. AMX, MET and VPZ triple therapy could be routinely analyzed in QC labs, in case of being co-formulated, using the presented method. Three different assessment tools were adopted revealing the benign environmental impact of presented method.

The presence of hiatal hernia is a significant predictor for symptomatic recurrence after cessation of vonoprazan therapy for gastroesophageal reflux disease: a long-term observational study

Background Gastroesophageal reflux disease (GERD) symptoms frequently recur after cessation of acid blockers. The presence of a hiatal hernia may worsen GERD symptoms and increase the risk of esophageal malignancy. The aim of this study is to clarify the timing and predictors for recurrence of GERD symptoms after cessation of vonoprazan (VPZ) therapy. Methods A retrospective observational study involved 86 patients who underwent cessation of VPZ therapy for symptomatic GERD. Collated data from medical record review included the endoscopic findings and Izumo scale score. Results The mean duration of continuous VPZ therapy before cessation was 7.9 months. GERD symptoms requiring the resumption of VPZ therapy recurred in 66 of 86 patients (77%). Kaplan-Meier analysis showed that overall recurrence-free rates at 6 months, one and two years after VPZ cessation were 44%, 32% and 23%, respectively. Alcohol use, the presence of a hiatal hernia and long-term therapy for more than six months were identified as significant positive predictors for symptomatic recurrence. Notably, hiatal hernia had the highest hazard ratio in both univariate and multivariate analyses. The recurrence-free rate in patients with a hiatal hernia was much lower at 6 months than in patients without a hiatal hernia (15% and 51%, respectively p = 0.002). After the symptomatic recurrence, GERD symptoms improved significantly after one-month VPZ therapy. Conclusion The rate of symptomatic recurrence after VPZ cessation in patients with GERD is considerable. Cessation of acid suppression therapy should be cautious in patients with both a hiatal hernia and GERD.

QUANTIFICATION AND QUALITY CONTROL OF TRIPLE-DRUG COMBINATION EMPLOYED FOR GASTRIC ULCER USING STABILITY-INDICATING SELECTIVE RP-HPLC TECHNIQUE

Objective: A seven-day regimen consisting of vonoprazan (VNP), amoxicillin (AXC) and clarithromycin (CRC), administered twice daily, has been permitted and reimbursed by health coverage as initial therapy. No technique has been implemented yet to determine the quantities of VNP, AXC, and CRC combination. This work effectively aimed at estimating these medications (VNP, AXC, and CRC) at the same time by developing an HPLC technique that saves money and time. Methods: The VNP, AXC, and CRC were separated in a “Waters” column (C18 nature; 250 mm sized length; 4.6 mm sized internal diameter; 5 µm sized particle; 25 °C temperature). Phosphoric acid (0.1% in water; pH 4.2) and absolute methanol (50:50, v/v) comprise the mobile phase. The drug product, Voqueznatripak, was subjected to hydrolysis, oxidation, photolysis, and thermal stressors with the intent to cause enforced degradation. The suggested "HPLC conditions" were verified in compliance with ICH guidance. Results: The measurements had a linear range of 10–20 µg/ml for VNP and 250–750 µg/ml for AXC and CRC. The AXC, CRC, and VNP had LOQ’s 5.302 µg/ml, 5.487 µg/ml and 0.523 µg/ml, respectively. Precision measurements were&lt;0.2% RSD and accuracy ranges were 99.40% to 101.46%. The newly devised “HPLC conditions” specificity attribute and stability-indicating quality were also validated by forced degradation tests. Conclusion: The newly devised “HPLC conditions” for analysing AXC, CRC, and VNP in formulation dosage form and stability samples might be adapted by quality control laboratories. The devised “HPLC conditions” is qualified and consistent to reveal and detect any probable change in the drug product assessments throughout stability experiments.

Comparison of vonoprazan dual therapy, quadruple therapy and standard quadruple therapy for Helicobacter pylori infection in Hainan: a single-center, open-label, non-inferiority, randomized controlled trial

ObjectiveTo compare the potential efficacy and safety of dual therapy and quadruple therapy with vonoprazan (VPZ) as well as the standard quadruple therapy of proton pump inhibitor (PPI) for the eradication of Helicobacter pylori (Hp) infection in Hainan province.MethodsA single-centre, non-blinded, non-inferiority randomized controlled trial was conducted at the outpatient department of gastroenterology at the Second Affiliated Hospital of Hainan Medical University from June 2022 to February 2023. 135 patients aged 18–75 years with Hp infection were enrolled and randomized into three different groups (group V1: VPZ 20 mg twice a day and amoxicillin 1.0 g three times a day for 14 days V2: vonoprazan 20 mg, amoxicillin capsules 1.0 g, furazolidone 0.1 g and bismuth potassiulm citrate 240 mg, twice daily for 14 days;; group V3: ilaprazole 5 mg, Amoxicillin 1.0 g, Furazolidone 100 mg, bismuth potassiulm citrate 240 mg, twice a day for 14 days). Four weeks after the end of treatment, Hp eradication was confirmed by rechecking 13C-urea breath test (UBT).ResultsThe eradication efficacy of V1 and V3 was non-inferior to that of V2, which is consistent with the results obtained from the Kruskal-Wallis H test. The eradication rate by intentional analysis was 84.4% (38/45, 95%CI 73.4%–95.5%, P>0.05) for all the three groups. If analyzed by per-protocol, the eradication rates were 88.4% (38/43, 95%CI 78.4%–98.4%), 92.7% (38/41, 95%CI 84.4%–101.0%),88.4% (38/43，95%CI 78.4%–98.4%) in groups V1, V2 and V3, respectively, which did not show a significant difference (P > 0.05). The incidence of adverse effects was significantly lower in VPZ dual therapy compared to the other two treatment regimens (P < 0.05). VPZ dual therapy or quadruple therapy was also relatively less costly than standard quadruple therapy.ConclusionVPZ dual therapy and quadruple therapy shows promise of not being worse than the standard quadruple therapy by a clinically relevant margin. More studies might be needed to definitively determine if the new therapy is equally effective or even superior.

Vonoprazan-amoxicillin dual therapy with different amoxicillin dosages for treatment-naive patients of Helicobacter pylori infection in China: a prospective, randomized controlled study.

The vonoprazan (VPZ)-amoxicillin (AMO) dual therapy (VA) demonstrates a satisfactory eradication rate for Helicobacter pylori (H. pylori ). However, the optimal dosage of AMO in this regimen remains uncertain. The objective of this study is to investigate the efficacy of different doses of AMO in the VA regimen for first-line treatment of H. pylori infection. A total of 192 treatment-naive H. pylori -infected patients were randomly assigned to one of three groups: low-dose VA (LD-VA: VPZ 20 mg b.i.d + AMO 750 mg t.i.d), moderate-dose VA (MD-VA:VPZ 20 mg b.i.d + AMO 1000 mg t.i.d), and high-dose VA (HD-VA: VPZ 20 mg b.i.d + AMO 1250 mg t.i.d). All groups received 14 days of treatment. The study evaluated and compared the eradication rates, adverse events (AEs), and patient compliance among the three groups. Eradication rates for LD-VA, MD-VA, and HD-VA were 76.6% (49/64), 79.7% (51/64), and 84.4% (54/64), respectively, as determined by intention-to-treat analysis; 90.6% (48/53), 94.3% (50/53), and 98.1% (53/54) according to per-protocol analysis; 89.1% (49/55), 94.4% (51/54), and 96.4% (54/56) with modified intention-to-treat analysis (all P > 0.05). Although not statistically significant, numerically higher eradication rates were observed with the higher dose AMO VA regimen. There were no statistically significant differences in the incidence of AEs and compliance among the three VA regimens. Fourteen-day VA regimens with AMO doses exceeding 2 g/day demonstrated satisfactory eradication rates. HD-VA therapy is potentially the most effective regimen. Large-sample clinical trials are required to further validate these findings.

Treatment of Helicobacter pylori with potassium competitive acid blockers: A systematic review and meta-analysis.

Helicobacter pylori (H. pylori) infects over half the global population, causing gastrointestinal diseases like dyspepsia, gastritis, duodenitis, peptic ulcers, G-MALT lymphoma, and gastric adenocarcinoma. Eradicating H. pylori is crucial for treating and preventing these conditions. While conventional proton pump inhibitor (PPI)-based triple therapy is effective, there's growing interest in longer acid suppression therapies. Potassium competitive acid blocker (P-CAB) triple and dual therapy are new regimens for H. pylori eradication. Initially used in Asian populations, vonoprazan (VPZ) has been recently Food and Drug Administration-approved for H. pylori eradication. To assess the efficacy of regimens containing P-CABs in eradicating H. pylori infection. This study, following PRISMA 2020 guidelines, conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials (RCTs) or observational studies with the following command: [("Helicobacter pylori" OR "H pylori") AND ("Treatment" OR "Therapy" OR "Eradication") AND ("Vonaprazan" OR "Potassium-Competitive Acid Blocker" OR "P-CAB" OR "PCAB" OR "Revaprazan" OR "Linaprazan" OR "Soraprazan" OR "Tegoprazan")]. Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H. pylori were included. Exclusion criteria included case reports, case series, unpublished trials, or conference abstracts. Data variables encompassed age, diagnosis method, sample sizes, study duration, intervention and control, and H. pylori eradication method were gathered by two independent reviewers. Meta-analysis was performed in R software, and forest plots were generated. A total of 256 references were initially retrieved through the search command. Ultimately, fifteen studies (7 RCTs, 7 retrospective observational studies, and 1 comparative unique study) were included, comparing P-CAB triple therapy to PPI triple therapy. The intention-to-treat analysis involved 8049 patients, with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies. The analysis revealed a significant difference in H. pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies [risk ratio (RR) = 1.17, 95% confidence interval (CI): 1.11-1.22, P < 0.0001] and (RR = 1.13, 95%CI: 1.09-1.17, P < 0.0001], respectively. However, no significant difference was found between tegoprazan (TPZ) triple therapy and PPI triple therapy in both RCTs and observational studies (RR = 1.04, 95%CI: 0.93-1.16, P = 0.5) and (RR = 1.03, 95%CI: 0.97-1.10, P = 0.3), respectively. VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H. pylori, positioning it as a highly effective first-line regimen. Additionally, TPZ-based triple therapy was non-inferior to classical PPI triple therapy.

Prevalence and risk factors for medication-refractory reflux esophagitis in patients with systemic sclerosis in Japan.

Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump inhibitor (PPI)-refractory reflux esophagitis (RE). The aims of this study were to clarify the current management of RE and prevalence and risk factors of medication-refractory RE in patients with SSc in Japan. A total of 188 consecutive patients with SSc who underwent both esophageal high-resolution manometry (HRM) and esophagogastroduodenoscopy (EGD) were reviewed. The presence of RE and grades of the gastroesophageal flap valve (GEFV) were assessed. Esophageal motility was assessed retrospectively according to the Chicago classification v3.0. When RE was seen on a standard dose of PPI or any dose of vonoprazan (VPZ), it was defined as medication-refractory RE. Approximately 80% of patients received maintenance therapy with acid secretion inhibitors regardless of esophageal motility abnormalities. Approximately 50% of patients received maintenance therapy with PPI, and approximately 30% of patients received VPZ. Medication-refractory RE was observed in 30 patients (16.0%). In multivariable analyses, the number of EGD and absent contractility were significant risk factors for medication-refractory RE. Furthermore, combined absent contractility and GEFV grade III or IV had higher odds ratios than did absent contractility alone. Patients with persistent reflux symptoms and those with absent contractility and GEFV grade III or IV should receive maintenance therapy with strong acid inhibition to prevent medication-refractory RE.

The development and validation of a stability indicating Rp-UPLC method for the simultaneous estimation of clarithromycin, amoxicillin, and vonoprazan in a physical mixture

A novel technique was developed for simultaneous quantification of clarithromycin (CLA) amoxicillin (AMO), and vonoprazan (VON) in a mixture using the reverse phase ultra-performance liquid chromatography (RP-UPLC) technique and validated as per International Council for Harmonization (ICH) guidelines as there was no literature published for its estimation by UPLC. The method was developed using an acquity UPLC system from waters corporation with Hibar Bis phosphonate C18 column (100 × 2.1 mm, 2 μm) at 35°C and tunable ultra-violet detector (TUV) with detection wavelength at 210 nm, has a run time of below 3 minutes. The mobile phase proportion of 60:40 of 0.1 N monobasic potassium phosphate buffer (pH 3.8) and acetonitrile at a flow velocity of 0.2 ml/ minute was utilized. Linearity was observed for CLA, AMO, and VON between the concentration ranges of 25–150, 25–150, and 1–6 μg/ml, respectively, and R2 was 0.999 for CLA, AMO, and VON. Accuracy and precision were within 2% of the coefficient of variation (RSD) for all drugs. The observed mean percentage recoveries for the CLA, AMO, and VON were determined to be 99.74%, 99.07%, and 99.8%, respectively. The stability of the approach was assessed using degradation studies by exposing it to acid, alkali, oxidizing agent, heat, Ultra Violet (UV) light, and water as per ICH guidelines.

Characteristics of proton pump inhibitor-resistant severe reflux esophagitis and efficacy of vonoprazan in elderly (older than 75 years) and non-elderly groups.

Previous studies on age differences in proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) have found that stenosis and bleeding complications were significantly more common in the elderly than in the non-elderly. We sought to examine differences between two groups of elderly (75 years or older) and non-elderly (<75 years) patients with (PPI)-resistant severe RE and also the efficacy of vonoprazan (VPZ) in these patients. There were 14 patients in the elderly group and 15 in the non-elderly group. Information was obtained on patient background (sex, body mass index [BMI], gastric mucosal atrophy, and the presence of hernia and collagen disease), and all patients underwent the saliva secretion test and esophagogastroduodenoscopy (EGD). The saliva secretion test (amount of saliva secreted, salivary pH, and the acid-buffering capacity) was performed by chewing sugar-free gum for 3 min before EGD. The efficacy of VPZ in both groups was also assessed. Saliva secretion, sex, BMI, and the presence of gastric mucosal atrophy did not significantly differ between the two groups. The number of hernias larger than 4 cm was significantly higher in the elderly PPI-resistant group, and significantly more patients had collagen disease in the non-elderly group. The efficacy of VPZ was not significantly different between the two groups; however, 10 patients in the non-elderly group had collagen disease, and 4 did not achieve esophageal mucosal healing even with VPZ 20 mg. The number of large hernias (>4 cm) was significantly higher in the elderly group, while significantly more non-elderly patients had collagen disease. In the non-elderly group with scleroderma, the efficacy of VPZ 20 mg may not be sufficient.