Therapeutic efficacy and drug safety comparison of one-week Vonoprazan triple therapy with two-weeks Esomeprazole triple therapy in Helicobacter pylori infection: Findings from a single-centre randomized clinical trial in population of Pakistan.

OBJECTIVE: To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection. METHODS: The randomised clinical trial was conducted from December 2022 to January 2023 at the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Gastroenterology Department of Pak Emirates Military Hospital, Rawalpindi, and comprised patients found positive for Helicobacter pylori by stool antigen test. They were randomly distributed into two groups. The EAL group received twoweek triple therapy with Esomeprazole 20mgand Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. The VAL group was prescribed one-week triple therapy with Vonoprazan 20mg and Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. Eradication success was evaluated by stool antigen test 4 weeks after starting the treatment. Safety of the therapy was assessed by noting adverse effects at days 3 and 14 of the treatment. Data was analysed using SPSS 27. RESULTS: Of the 122 patients, there were 61(50%) in each of the 2 groups; 30(49.2%) males and 31(50.8%) females with mean age 38.40±12.25 years in group EAL, and 35(57.4%) males and 26(42.6%) females with mean age 40.98±12.13 years in VAL group. In the EAL group, 57(93.4%) patients were found to be free of Helicobacter pylori infection compared to 58(95%) in the VAL group. Nausea 14(23%), bitter taste 41(67.2%), abdominal pain 16(26.2%) and headache 20(32.8%) were the adverse effects that were significantly more common in the EAL group compared to the VAL group B. CONCLUSIONS: Vonoprazan-based triple therapy was found to be more effective with less reported adverse effects and potential benefits of better patient compliance due to shorter therapy duration. Clinical Trial Number: Iranian Registry of Clinical Trials: IRCT20221207056738N1.

Antibiomania: A Case Report of a Manic Episode Potentially Induced by the Interaction of Clarithromycin and Amoxicillin during H. Pylori Eradication Therapy.

Antibiomanic episodes, or as the DSM-5 refers to them, drug-induced manic episodes, pose a clinical challenge that is still poorly understood. There is insufficient information on the most common clinical presentation, patient profile, or underlying aetiopathogenic mechanisms. We present the clinical case of a 67-year-old woman who, after starting treatment (clarithromycin and amoxicillin) for the eradication of Helicobacter pylori, bacteria presented with a brief manic episode, which resolved after withdrawal of both drugs and with antipsychotic treatment. The possible interaction of both drugs, as GABA antagonists, in the generation of such episodes is discussed, and the clinical importance of such episodes in psychiatric emergency departments and liaison and interconsultation psychiatry, is highlighted.

Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial.

BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Antibiomania: A Case Report of a Manic Episode Potentially Induced by the Interaction of Clarithromycin and Amoxicillin during H. Pylori Eradication Therapy

Antibiomanic episodes, or as the DSM-5 refers to them, drug-induced manic episodes, pose a clinical challenge that is still poorly understood. There is insufficient information on the most common clinical presentation, patient profile, or underlying aetiopathogenic mechanisms. We present the clinical case of a 67-year-old woman who, after starting treatment (clarithromycin and amoxicillin) for the eradication of Helicobacter pylori, bacteria presented with a brief manic episode, which resolved after withdrawal of both drugs and with antipsychotic treatment. The possible interaction of both drugs, as GABA antagonists, in the generation of such episodes is discussed, and the clinical importance of such episodes in psychiatric emergency departments and liaison and interconsultation psychiatry, is highlighted. (AU)

Cardiac events after using clarithromycin for anti-Helicobacter pylori therapy in patients with coronary artery disease.

Clarithromycin is an antibiotic commonly used to treat Helicobacter pylori infections. The US Food and Drug Administration (FDA) advises caution before prescribing clarithromycin to patients with cardiac diseases. This study aimed to evaluate cardiac events after anti-H pylori treatment in patients with coronary artery disease. A retrospective 5-year study was conducted on outpatients who received anti-H pylori therapy. Among the 7855 patients receiving therapy, 228 patients (2.9%) underwent angiography with coronary artery disease before therapy, and 193 patients received clarithromycin. Clarithromycin users seemed not to be at risk for cardiac events as compared with non-clarithromycin users at 3 months (4.7% vs 2.9%, P = .63) and 1 year (10.9% vs 5.7%, P = .35). Neither life-threatening dysrhythmia nor cardiac death was noted. The risk factors for cardiac events within 3 months after therapy were smoker (OR:5.38, 95% CI:1.39-20.78), and events within 1 year were smoker (OR:3.8, 95% CI:1.41-10.22), and diabetes mellitus (OR:5.68, 95% CI:1.9-16.98). Among patients with coronary artery disease who received anti-H pylori therapy, short-term cardiac events did not increase in clarithromycin users but should be considered in diabetic and smoking patients.

Efficacy and safety of a 14-day modified concomitant therapy for refractory Helicobacter pylori infection: a pilot study.

BACKGROUND AND AIM: After three treatment failures, Helicobacter pylori infection is deemed refractory as antibiotic treatment options become significantly limited. This study evaluated the efficacy and safety of a 14-day modified concomitant therapy for managing refractory H. pylori infection. METHODS: Patients who had failed to respond to three or more rounds of H. pylori therapies were recruited for this study. They received a 14-day modified concomitant therapy, including esomeprazole 40 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily and tetracycline 500 mg four times daily. Demographic data, adverse events, and patient compliance were recorded. The presence of H. pylori was reevaluated 6 weeks following treatment. Eradication rate was assessed as the primary outcome. RESULTS: Overall, 59 participants received the 14-day modified concomitant therapy. In the intention-to-treat and per-protocol analyses, the eradication rate was 84.7% (50/59) and 89.3% (50/56), respectively. H. pylori was successfully isolated from 75.0% (12/16) of patients. The resistance rate of H. pylori to metronidazole, levofloxacin, and clarithromycin was 91.7% (11/12), 58.3% (7/12), and 50.0% (6/12), respectively. Resistance to amoxicillin, furazolidone, or tetracycline was not observed. The frequency of adverse events was 35.6% (21/59), with no serious adverse events reported. CONCLUSION: The 14-day modified concomitant therapy appears to be appropriate for refractory H. pylori infection and is particularly promising for the Chinese population. A randomized controlled trial is warranted to verify its efficacy, especially in the current environment of increasing antibiotic resistance.

[Cushing's syndrome with inhaled corticosteroid: Drug interactions to avoid]. / Syndrome de Cushing sous fluticasone inhalée : interactions médicamenteuses à éviter.

Cushing's syndrome is an iatrogenic event occurring during co-administration of inhaled corticosteroids and potent inhibitors of P450 cytochromes. We report the clinical case of a 29-year-old woman with a past history of asthma treated with inhaled fluticasone propionate (FP), chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis (ABPA) treated with itraconazole (ITZ), and Mycobacterium xenopi infection treated with moxifloxacin (MXF), ethambutol (EMB) and clarithromycin (CLR). Four months after initiation of antibiotic and antifungal medication, the patient contracted Cushing's syndrome. Its etiology consisted in interaction between FP, ITZ and CLR, which led to pronouncedly increased corticosteroid concentrations in circulating plasma cells. Following on the one hand cessation of FP and ITZ and on the other hand hydrocortisone supplementation, evolution was favorable. Several cases of iatrogenic Cushing's syndrome induced by co-administration of FP and potent CYP3A4 inhibitors have been reported in the literature. If possible, FP should be avoided in patients being treated with CYP3A4 inhibitors. Due to its differing physicochemical properties, beclometasone may be considered as the safest therapeutic alternative.

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

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

Physiologically based pharmacokinetic modeling to assess the drug-drug interactions of anaprazole with clarithromycin and amoxicillin in patients undergoing eradication therapy of H. pylori infection.

OBJECTIVE: This study aimed to assess the pharmacokinetic (PK) interactions of anaprazole, clarithromycin, and amoxicillin using physiologically based pharmacokinetic (PBPK) models. METHODS: The PBPK models for anaprazole, clarithromycin, and amoxicillin were constructed using the GastroPlus™ software (Version 9.7) based on the physicochemical data and PK parameters obtained from literature, then were optimized and validated in healthy subjects to predict the plasma concentration-time profiles of these three drugs and assess the predictive performance of each model. According to the analysis of the properties of each drug, the developed and validated models were applied to evaluate potential drug-drug interactions (DDIs) of anaprazole, clarithromycin, and amoxicillin. RESULTS: The developed PBPK models properly described the pharmacokinetics of anaprazole, clarithromycin, and amoxicillin well, and all predicted PK parameters (Cmax,ss, AUC0-τ,ss) ratios were within 2.0-fold of the observed values. Furthermore, the application of these models to predict the anaprazole-clarithromycin and anaprazole-amoxicillin DDIs demonstrates their good performance, with the predicted DDI Cmax,ss ratios and DDI AUC0-τ,ss ratios within 1.25-fold of the observed values, and all predicted DDI Cmax,ss, and AUC0-τ,ss ratios within 2.0-fold. The simulated results show no need to adjust the dosage when co-administered with anaprazole in patients undergoing eradication therapy of H. pylori infection since the dose remained in the therapeutic range. CONCLUSION: The whole-body PBPK models of anaprazole, clarithromycin, and amoxicillin were built and qualified, which can predict DDIs that are mediated by gastric pH change and inhibition of metabolic enzymes, providing a mechanistic understanding of the DDIs observed in the clinic of clarithromycin, amoxicillin with anaprazole.

Diagnostic and Treatment Practices for Helicobacter Pylori Infection in an Academic Pediatric Hospital.

BACKGROUND: In 2016, ESPGHAN/NASPGHAN issued revised guidelines for the management of Helicobacter pylori (H. pylori) infection in children and adolescents. Recommendations include performing antibiotic susceptibility testing to tailor therapy. The aim of our study was to evaluate the H. pylori treatment landscape in pediatric patients at our institution. METHODS: We performed a retrospective study of patients diagnosed with H. pylori infection at a single academic children's hospital from 2015 to 2021. The frequency of each treatment regimen and their respective eradication rates were calculated. We compared trends in antibiotic prescriptions and eradication rates before and after 2016. RESULTS: One hundred and ninety-six patients were included. Triple therapy with amoxicillin, clarithromycin, and a proton pump inhibiter (PPI) was the most often prescribed regimen (46.5%), followed by amoxicillin, metronidazole, and PPI (33%). Eradication rates were 70% for amoxicillin, clarithromycin, and PPI and 64% for amoxicillin, metronidazole, and PPI. CONCLUSION: Our results show eradication rates for both regimens were comparable but suboptimal, highlighting the need to incorporate resistance testing into broader practice.

Ten-day tegoprazan-based concomitant therapy as a first-line treatment for Helicobacter pylori eradication.

BACKGROUND/AIMS: Tegoprazan, a novel potassium-competitive acid blocker, has shown rapid action and gastric acid inhibition. In this study, we evaluated the efficacy of a tegoprazan-based, nonbismuth-containing quadruple (concomitant) therapy for the primary eradication of Helicobacter pylori. METHODS: We conducted a prospective, single-arm, single-center, primitive study to verify the efficacy of a 10-day tegoprazan- based (50-mg dose) concomitant therapy, including amoxicillin (1,000-mg dose), clarithromycin (CLA; 500-mg dose), and metronidazole (MET; 500-mg dose) twice daily as a first-line treatment for H. pylori eradication. RESULTS: We tested consecutive cultures for antibiotic susceptibility and minimum inhibitory concentrations. We enrolled 84 participants; 79 (94.0%) completed first-line therapy. The overall intention-to-treat and per-protocol eradication rates were 90.5% (95% confidence interval [CI], 82.1-95.8) and 96.2% (95% CI, 83.4-97.6), respectively. Of the 73 participants evaluated for antibiotic resistance, 19 (26.0%), 32 (42.5%), and 8 (11.0%) exhibited CLA, MET, and CLA and MET dual resistance, respectively. Of these, 39 participants (66.1%) exhibited successful eradication after the therapeutic regimen despite antibiotic resistance. CONCLUSION: The 10-day tegoprazan-based concomitant therapy may be an effective first-line treatment for eradicating H. pylori.

Susceptibility-guided sequential strategy versus empirical therapy for Helicobacter pylori infection: study protocol for a randomised controlled trial.

BACKGROUND: New treatment strategies are required against infections caused by Helicobacter pylori, which grows increasingly resistant to antibiotics. Polymerase chain reaction-based methods for antibiotic susceptibility testing are available for detecting H. pylori-specific mutations that confer resistance to clarithromycin and levofloxacin. Several meta-analyses have compared eradication rates for susceptibility-guided versus empirical therapy for H. pylori treatment; however, all have significant limitations and high heterogeneity, and the results are contradictory. The main objective of this trial is to assess whether a sequential strategy based on molecular susceptibility testing-guided therapy for H. pylori has a better eradication rate than empirical therapy. METHODS: This trial is designed as a prospective, randomised, open-label, active-controlled and single-centre study. Men and women who are H. pylori-positive, naïve to treatment, and aged 18-65 years will be recruited. A total of 500 participants will be randomised to receive either empirical therapy or a susceptibility-guided sequential strategy. Bismuth quadruple therapy will be the empirical first-line therapy, and in case of failure, high-dose dual (proton-pump inhibitor + amoxicillin) treatment will be the rescue therapy. For the susceptibility-guided sequential strategy, regimen selection will be based on H. pylori susceptibility to clarithromycin (first-line) and levofloxacin (rescue). A first-line treatment of clarithromycin triple therapy will be selected for clarithromycin-sensitive strains. For clarithromycin resistance, a high-dose dual therapy will be selected. During the rescue treatment, a levofloxacin quadruple regimen will be selected for levofloxacin-sensitive strains, and a furazolidone quadruple regimen will be selected for others. The primary outcome is the first-line eradication rate in both groups, and the overall (including first and rescue therapies) H. pylori eradication rate in both groups is one of the secondary outcomes. The eradication rates of H. pylori will be analysed by intention-to-treat analysis, modified intention-to-treat analysis, and per-protocol analysis. DISCUSSION: This randomised controlled trial will provide objective and valid evidence about the value of polymerase chain reaction-based molecular methods for antibiotic susceptibility testing in guiding H. pylori eradication. TRIAL REGISTRATION: Clinicaltrials.gov NCT05549115. Released on 18 September 2022. First posted on 22 September 2022. Enrolment of the first participant on 20 September 2022. The study is retrospectively registered.

Combination of vonoprazan and amoxicillin as the first-line Helicobacter pylori eradication therapy: a multicenter, prospective, randomized, parallel-controlled study.

The eradication rate of Helicobacter pylori (H. pylori) decreased gradually. This study aimed to analyze the efficacy and safety of a 14-day combination of vonoprazan and amoxicillin as the first-line eradication therapy for H. pylori infection and compared them with those of the bismuth quadruple therapy. A prospective randomized clinical trial (RCT) was designed, involving patients with H. pylori infection in 6 institutions who did not receive any treatment yet. They were randomly assigned into the VA-dual group (vonoprazan 20 mg b.i.d + amoxicillin 750 mg q.i.d) or EACP-quadruple group (esomeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg + colloidal bismuth subcitrate 220 mg b.i.d) for 14 days in a ratio of 1:1. At least 28 days later, the eradication rate was detected by the 13C-urea breath test (UBT). A total of 562 patients from February 2022 to September 2022 were enrolled and 316 were random. In the ITT analysis, the eradication rates of H. pylori in the VA-dual group and EACP-quadruple group were 89.9% and 81.0%, respectively, p = 0.037. In the PP analysis were 97.9% and 90.8%, p = 0.009. The different eradication rate was 8.9% (95% CI 1.2-16.5%) and 7.2% (95% CI 1.8-12.4%) in ITT and PP analyses, both lower limit of the 95%CI was still higher than the prespecified margin. In addition, the incidence of adverse events in the VA-dual group was significantly lower than that in the EACP-quadruple group (19.0% vs. 43.0%, P < 0.001). The efficacy and safety of a 14-day combination therapy of vonoprazan and amoxicillin in eradicating H. pylori are superior to bismuth quadruple therapy, and this combination significantly reduces the use of antibiotics.

Vonoprazan With Amoxicillin or Amoxicillin and Clarithromycin for the Treatment of Helicobacter pylori Infection.

OBJECTIVES: 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. DATA SOURCES: 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. STUDY SELECTION AND DATA EXTRACTION: 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. DATA SYNTHESIS: 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. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: 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. CONCLUSION: 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.

Hyperkalemia by eplerenone or esaxerenone in the presence or absence of clarithromycin in hypertensive patients: a retrospective observational cohort study.

OBJECTIVE: Mineralocorticoid receptor antagonists (MRAs), eplerenone and esaxerenone, cause hyperkalemia dose-dependently. We investigated the cytochrome P450 3A4-mediated drug-drug interaction between the MRAs and clarithromycin. METHODS: This retrospective observational study included adult hypertensive patients with MRA plus clarithromycin or MRA alone with a propensity score matching (1:1). The difference in serum potassium level (ΔK, maximum level - baseline level) between groups was compared using the Mann-Whitney U -test. Linear regression analysis was used to detect variables that correlated with ΔK in patients with MRA plus clarithromycin. RESULTS: After propensity score matching (each nine patients), serum potassium level was elevated after treatment with MRA plus clarithromycin [4.3 (3.5 to 5.1) meq/l to 4.9 (4.0 to 5.5) meq/l, P  = 0.0234] and MRA alone [4.3 (4.0 to 4.7) meq/l to 4.6 (4.4 to 5.2) meq/l, P  = 0.0469]. Although there was no significant difference in ΔK between groups [MRA plus clarithromycin: 0.5 (0.1 to 1.1) meq/l vs. MRA alone: 0.3 (0.1 to 1.2) meq/l, P  = 0.7231], ΔK was significantly higher in esaxerenone plus clarithromycin than in esaxerenone alone [0.6 (0.5 to 1.1) meq/l vs. 0.1 (0.1 to 0.2) meq/l, P  = 0.0495]. Conversely, clarithromycin did not show a significant effect on ΔK in patients with eplerenone [0.4 (-0.2 to 1.2) meq/l vs. 0.8 (0.1 to 1.3) meq/l, P  = 0.5745]. A positive correlation was found between ΔK and age in patients with MRA plus clarithromycin ( y  = 0.03 ×  x - 1.38, r  = 0.71, P  = 0.0336). CONCLUSION: The drug-drug interaction between MRAs and clarithromycin was evident, particularly in esaxerenone. Serum potassium levels should be closely monitored in older patients.

Effectiveness and safety of vonoprazan-based regimens compared with those of proton pump inhibitor (PPI)-based regimens as first-line agents for Helicobacter pylori: a meta-analysis of randomized clinical trials.

PURPOSE: Vonoprazan (VPZ), a reversible H+-K+ ATPase inhibitor, has a relatively fast and sustained acid-suppression action that is unaffected by diet or gene polymorphisms. Several randomized controlled trials have evaluated the difference in the eradication rate of Helicobacter pylori (HP) between VPZ-based and proton pump inhibitor (PPI)-based regimens. The present review aimed to (1) evaluate the efficacy, safety, and compliance of VPZ-based regimens compared with those of PPI-based regimens as first-line treatments for HP infection and (2) perform a subgroup analysis to examine the influence of differences in clarithromycin-resistance status, treatment duration, treatment regimens, and research region on treatment outcomes. METHODS: We conducted a systematic literature search on PubMed, Embase, Cochrane Library, Web of Science, and ChiCTR Register. Systematic searches, study selection, data extraction, risk of bias assessment, and statistical analysis were performed according to pre-registered protocol on the PROSPERO (CRD42022336608). RESULTS: Eight studies and 2956 HP-infected patients were enrolled. Only first-line therapy and RCT study were considered. VPZ-based group had a superior eradication efficacy compared to PPI-based group by intention-to-treat (ITT) (pooled risk ratio (RR): 1.14, 95% CI: 1.08-1.21, p < 0.00001) and per-protocol analysis (pooled RR: 1.13, 95% CI: 1.07-1.20, p < 0.00001). This finding was further validated by subgroup analysis depending on treatment regimens, duration, region, and clarithromycin resistance. In addition, there was no significant difference in adverse events (p = 0.33) and compliances (p = 0.30) between the regimens. CONCLUSION: The VPZ-based regimens showed a superior eradication efficacy compared to the already frequently used PPI-based regimens. Furthermore, VPZ-based therapy showed comparable tolerability and incidence of adverse events.