Comparison of the Efficacy of 12-day Concomitant Quadruple Therapy versus 14-day High dose Dual Therapy as a First-line H. pylori Eradication Regimen.

Background/Aims: Helicobacter pylori (H. pylori) is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. Methods: In this RCT, we assigned 223 patients with H. pylori infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). H. pylori eradication was assessed eight weeks after the end of treatment. Results: H. pylori eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001). Conclusions: Twelve-day concomitant therapy seems to be an acceptable regimen for first-line H. pylori eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.

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.

Time interval of esomeprazole and dual antiplatelet therapy in patients with cardiocerebrovascular diseases.

Dual antiplatelet therapy (DAPT) with the combination of clopidogrel and aspirin is recommended for preventing secondary ischemic events in patients with acute coronary syndrome (ACS) or acute ischemic stroke (AIS). Proton pump inhibitors (PPIs) are suggested as preventive treatment for these patients. Due to clopidogrel-PPI interactions, separating their administration might be considered. However, a paucity of studies has been conducted to investigate the outcome differences between concurrent and interval-based use in ACS and AIS patients. Our study aimed to evaluate clinical outcomes based on administration timing. This study included patients with ACS or AIS onset or recurrence of within the last month. Patients who were expected to receive DAPT for at least 6 months and who were currently taking or planning to take esomeprazole were included. Patients were divided into Group 1 (interval administration group, IA group) and Group 2 (concurrent administration group, CA group) according to the interval between esomeprazole and DAPT administration. The time interval was based on 12 hours. The primary outcome was the occurrence of major adverse cardiocerebrovascular events (MACCEs), and safety outcomes were defined as major bleeding, minor bleeding and gastrointestinal bleeding and intracranial hemorrhage. A total of 3600 patients completed this study. The proportions of patients in the 2 groups were as follows: CA group, 99% (n = 3489) and IA group, 1% (n = 111). The primary outcome occurred in 0.9% of patients in the IA group and 1.8% of patients in the CA group (P = .51). There was no significant distinction in the overall bleeding risk of the CA group compared to that of the IA group (2.75% in the CA group and 2.70% in the IA group). Additionally, there was no significant difference observed between the 2 groups for safety outcomes. This multicenter, prospective, observational study that enrolled patients with ACS or AIS demonstrated that there was no significant difference in the occurrence of MACCEs and bleeding issues within 6 months according to the medication administration interval. The majority of patients with DAPT were taking PPIs simultaneously in real-world practice.

The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study.

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

Eradication rate and adherence with high-dose amoxicillin and proton pump inhibitor as first-line treatment for Helicobacter pylori infection: Experience from University Hospital in Chile.

INTRODUCTION: In Chile, more than 70% of adults are infected by Helicobacter pylori. Clarithromycin should not be used in any regimen if there is >15% resistance to this antibiotic, being greater than 26% in our population. In this scenario, the effectiveness of triple therapy (proton pump inhibitor [PPI], clarithromycin, amoxicillin) was only 63.8%. AIM: To evaluate the eradication rate and safety of dual therapy (esomeprazole and amoxicillin) in high doses, through a prospective, observational, and descriptive study. METHODS: Patients with a positive urease test obtained in an upper digestive endoscopy were included. Any other previous H. pylori eradication regimen were excluded. All patients were treated with esomeprazole 40 mg three times a day and amoxicillin 750 mg four times a day for 14 days. The eradication rate of the dual therapy was evaluated with the H. pylori stool antigen test (the Pylori-Strip® test used) 6 weeks after completing the eradication treatment and with at least 14 days without PPI, being a negative result, confirmation of the effectiveness of this regimen. RESULTS: Of 122 patients, 106 had a negative H. pylori antigen in stool; The intention-to-treat and per protocol analysis, the eradication rates were 91.8% [95% CI: 87%-97%] and 94% [95% CI: 90%-98%], respectively. Four patients discontinued treatment due to adverse effects. Smoking and adherence to treatment were associated with eradication rate. CONCLUSIONS: In this cohort of patients with H. pylori infection, high-dose dual therapy has a high eradication rate and good adherence, raising the possibility that it could be used as first-line therapy in our country. Studies with a larger number of patients should confirm these results.

Gastroprotective effect of rhodanine and 2,4-thiazolidinediones scaffolds in rat stomachs by contribution of anti-apoptotic (BCL-2) and tumor suppressor (P53) proteins.

In recent times, the methods used to evaluate gastric ulcer healing worldwide have been based on visual examinations and estimating ulcer dimensions in experimental animals. In this study, the protective effect of rhodanine and 2,4-thiazolidinediones scaffolds compared to esomeprazole was investigated in an ethanol model of stomach ulcers in rats. Pretreatment with experimental treatments or esomeprazole prevented the development of ethanol-induced gastric ulcers. The severity of the lesions and injuries was significantly lower than that of vehicle (10% Tween 80) treated rats. Significant and excellent results were obtained with the compound 6 group, with inhibition percentage and ulcer area values of 97.8% and 12.8 ± 1.1 mm2, respectively. Synthesized compounds 2, 7 and 8 exhibited inhibition percentages and ulcer areas of 94.3% and 31.2 ± 1.1 mm2, 91. 3% and 48.1 ± 0. 8 mm2, 89. 5% and 57. 6 ± 1. 2 mm2, and 89. 1% and 60.3 ± 0. 8 mm2, respectively. These biological outcomes are consistent with the docking studies in which Compounds 7 and 8 showed remarkable binding site affinities toward human H+/K+-ATPase α protein (ID: P20648), rat H+/K+-ATPase α protein (ID: P09626), and Na+/K+-ATPase crystal structure (PDB ID:2ZXE) with binding site energies of - 10.7, - 9.0, and - 10.4 (kcal/mol) and - 8.7, - 8.5, and - 8.0 (kcal/mol), respectively. These results indicate that these test samples were as effective as esomeprazole. Likewise, immunohistochemical staining of antiapoptotic (BCL2) and tumor suppressor (P53) proteins showed strong positive marks in the10% Tween 80- treated group, opposing the mild staining results for the esomeprazole-treated group. Similarly, the staining intensity of the group treated with Compounds 2-8 was variable for both proteins.

Co prescription of anti-acid therapy reduces the bioavailability of mycophenolate mofetil in systemic sclerosis patients: A crossover trial.

OBJECTIVE: Mycophenolate mofetil (MMF) is an effective treatment option for interstitial lung disease (ILD) in systemic sclerosis (SSc). Many patients require co-administration of proton pump inhibitors (PPI) or H2 receptor blockers (HRB) because of various gastrointestinal (GI) manifestations in SSc. Co-treatment with PPI or HRB have shown to reduce serum drug levels in post-transplant patients. We wanted to see if there is a similar phenomenon for Mycophenolate in SSc. METHODS: Twenty SSc patients, who were on a stable dose of MMF (1.5-3 g) underwent a sequential cross over study with MMF alone in the first month, followed by co-treatment with Ranitidine and then Esomeprazole in the second and third month respectively. Estimation of 12-hour area under curve (AUC) of Mycophenolic Acid (MPA) levels and total GI score were calculated at the end of each month and compared between the treatment arms. [Trial registration: CTRI/2020/06/025,939] RESULTS: Co-administration of esomeprazole was associated with 32.7% (mean difference = 22.28 µg h ml-1) reduction in mean AUC MPA, whereas ranitidine caused a reduction of 21.97% (mean difference = 14.93 µg h ml-1) in MPA AUC when compared to MMF without anti-acid therapies. The addition of ranitidine or esomeprazole resulted in significant reduction in the total GI score. CONCLUSION: Co-administration of PPI or HRB can significantly reduce the bioavailability of MMF in patients with SSc. To avoid therapeutic failure of MMF drug level monitoring is essential when these agents are co-prescribed with MMF.

Effect of esomeprazole with and without a probiotic on fecal dysbiosis, intestinal inflammation, and fecal short-chain fatty acid concentrations in healthy dogs.

BACKGROUND: Proton pump inhibitors can cause diarrhea and a transient increase in fecal dysbiosis index in dogs. It is unknown if concurrent probiotic administration mitigates these effects. OBJECTIVE/HYPOTHESIS: To assess the fecal Canine Microbial Dysbiosis Index (CMDI), fecal short chain fatty acid (SCFA), and fecal calprotectin concentrations in dogs administered esomeprazole with and without a probiotic. ANIMALS: Eleven healthy dogs. METHODS: Prospective, within-subjects before and after study. All dogs received 7-day courses of esomeprazole (1 mg/kg PO q 24h) alone followed by esomeprazole with a probiotic (15 billion CFU/kg), separated by a 4-week washout period. Data were compared between phases using mixed effects ANOVA or generalized estimating equations with post-hoc Holm adjustment for 2-way comparisons. RESULTS: Compared to baseline (mean CMDI -2.66, SD 3.04), fecal CMDI was not different with esomeprazole administration alone (mean CMDI -1.48, SD 3.32, P = .08), but there was a significant increase (Diff 3.05, 95% CI [1.37, 4.74], P < .001, Effect size 2.02) when esomeprazole and a probiotic were administered concurrently (mean CMDI 0.39, SD 2.83). CMDI was significantly higher when esomeprazole was administered with a probiotic than alone (Diff 1.87, 95% CI [0.19, 1.87], P = .02, Effect size 1.24). Fecal calprotectin and SCFA concentrations did not differ between phases. The occurrence of vomiting and diarrhea was not different from baseline when esomeprazole was administered alone (36%/27%) or with a probiotic (46%/9%). CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy dogs, concurrent administration of a probiotic is unlikely to lessen adverse effects associated with esomeprazole administration.

Efficacy and safety of vonoprazan-based dual therapy and esomeprazole-based dual therapy in eradicating primary Helicobacter pylori infection: A propensity score matching analysis.

BACKGROUND: According to the Maastricht VI/Florence consensus report, potassium-competitive acid blockers (P-CAB) may improve Helicobacter pylori eradication treatment. MATERIALS AND METHODS: A total of 213 H. pylori treatment-naive patients aged between 18 and 70 years were treated with two regimens. The two regimens are VDT: 20 mg vonoprazan twice a day and 1 g amoxicillin three times daily and EDT: 20 mg esomeprazole four times a day and 750 mg amoxicillin four times daily. 13 C-urea breath tests were used to evaluate eradication rate 4-6 weeks after treatment. Based on propensity score matching (PSM), this retrospective study analyzed the eradication rates, adverse events (AEs), compliance, and antibiotic resistance rates in VDT and EDT groups. RESULTS: On intention-to-treat (ITT) analysis, the eradication rate in VDT group (89.0%; 95% CI 81.7-96.3) was non-inferior to that in EDT group (87.7%; 95% CI 80.1-95.3; p = 0.796). The corresponding per-protocol (PP) eradication rates were 94.1% (95% CI 88.4-99.8) and 92.8% (95% CI 86.7-98.9; p = 1.000), respectively. There were no significant between-group differences with respect to compliance or incidence of AEs. CONCLUSIONS: The efficacy and safety of 14-day VDT and EDT were comparable. Therefore, 14-day VDT or EDT may be recommended for the first-line treatment of H. pylori infection.

Pharmacokinetics, Bioequivalence, and Safety of Esomeprazole Magnesium Enteric-Coated Capsules in Healthy Chinese Subjects.

This bioequivalence study is critically important for drug production. Recently, a local pharmaceutical company produced esomeprazole magnesium enteric-coated capsules, a major drug to help to eradicate Helicobacter pylori, but the bioequivalence is not well known. The present study aimed to evaluate the bioequivalence of the 2 esomeprazole magnesium enteric-coated capsules and their pharmacokinetics and safety in 3 biological equivalence trials: fasting, feeding, and mixing. The fasting and mixing trials used single-centered randomized, open-label, single-dose, 2-treatment, 2-period, and 2-sequence crossover design, while the fed trials used single-centered, randomized, open-label, single-dose, 2-treatment, 3-period, 3-sequence partial crossover design. For the fasting and mixing trials, each of the 32 subjects was fasted overnight prior to taking the test preparations or reference preparations. In the fed trial, 54 subjects were given a high-fat meal 1 hour before the drugs were administered. Blood specimens from all subjects were collected against the light within 14 hours, with the plasma drug concentration being detected by the validated ultra-performance liquid chromatography-tandem mass spectrometry analysis method. Geometric mean ratio of maximum concentration, the area under the concentration-time curve from time zero to the last measurable concentration, and area under the concentration-time curve from time zero to infinity with 90% confidence interval were calculated. The data from fasting, mixing, and fed trials met the bioequivalence criteria. No serious adverse reactions were found, suggesting that the test and reference preparations of esomeprazole magnesium enteric capsules have similar safety profile.

Rifabutin-Containing Triple Therapy Versus Bismuth Quadruple Therapy for Helicobacter pylori Rescue Treatment: A Multicenter, Randomized Controlled Trial.

BACKGROUND: We compared the efficacy and safety of rifabutin-containing triple therapy with bismuth quadruple therapy for rescue treatment of Helicobacter pylori. METHODS: This was a noninferiority study trial of H. pylori treatment for subjects who had failed at least 2 prior treatments. Subjects were randomly assigned to receive rifabutin triple therapy with 14-day esomeprazole (20 mg), amoxicillin (1.0 g), and rifabutin (150 mg) twice a day; or bismuth quadruple therapy with esomeprazole (20 mg) and bismuth (220 mg) twice a day, plus metronidazole (400 mg) and tetracycline (500 mg) 4 times a day. Antimicrobial susceptibility was assessed by agar dilution and E-test. RESULTS: From May 2021 to October 2022, a total of 364 subjects were randomized. The eradication rates by intention-to-treat, per-protocol, and modified intention-to-treat were 89.0% (162/182; 95% confidence interval [CI], 83.6%-92.8%), 94.0% (157/167; 95% CI, 89.3%-96.7%), and 93.6% (162/173; 95% CI, 89.0%-96.4%) for rifabutin triple group. For bismuth quadruple group, they were 89.6% (163/182; 95% CI, 84.3%-93.2%), 95.3% (143/150; 95% CI, 90.7%-97.7%), and 93.7% (163/174; 95% CI, 89.0%-96.4%). CONCLUSIONS: The rifabutin triple therapy is an alternative to classical bismuth quadruple therapy for the rescue treatment of H. pylori with fewer side effects and higher compliance. CLINICAL TRIALS REGISTRATION: NCT04879992.

Bismuth, esomeprazole, metronidazole, and minocycline or tetracycline as a first-line regimen for Helicobacter pylori eradication: A randomized controlled trial.

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

NLRP3 inhibition improves maternal hypertension, inflammation, and vascular dysfunction in response to placental ischemia.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder with end-organ damage that presents after 20 wk of gestation. PE pathophysiology often includes vascular dysfunction and increased inflammation that continues to damage patient health even after PE resolves. Currently, there is no cure for PE beyond delivery of the fetal-placental unit. Previous clinical studies have identified elevated placental NLRP3 expression in patients with PE and suggest NLRP3 as a potential therapeutic target. In this study, we examined the effect of NLRP3 inhibition on PE pathophysiology in the reduced uterine perfusion pressure (RUPP) model rat using MCC950 (20 mg/kg/day) or esomeprazole (3.5 mg/kg/day). We hypothesized that increased NLRP3 in response to placental ischemia impairs anti-inflammatory IL-33 signaling to induce T-helper 17 cell (TH17) and cytolytic NK cell (cNK) activation, which is known to mediate oxidative stress and vascular dysfunction leading to maternal HTN and intrauterine growth restriction. RUPP rats had significantly higher placental NLRP3 expression, maternal blood pressure, fetal reabsorption rate, vascular resistance, oxidative stress, cNKs and TH17s, and decreased IL-33 compared with normal pregnant (NP) rats. NLRP3 inhibition, with either treatment, significantly reduced placental NLRP3 expression, maternal blood pressure, fetal reabsorption rates, vascular resistance, oxidative stress, cNK, and TH17 populations in RUPP rats. Based on our findings, NLRP3 inhibition reduces PE pathophysiology and esomeprazole may be a potential therapeutic for PE treatment.

Helicobacter pylori eradication rates using clarithromycin and levofloxacin-based regimens in patients with previous COVID-19 treatment: a randomized clinical trial.

BACKGROUND: Helicobacter pylori (H. pylori) is affecting half of the globe. It is considered a main causative organism of chronic gastritis, peptic ulcer disease, and different gastric maliganacies. It has been also correlated to extraintestinal diseases, including refractory iron deficiency anaemia, vitamin B12 deficiency, and immune thrombocytopenic purpura. The misuse of antibiotics during the coronavirus diseases 2019 (COVID-19) pandemic time can affect H. pylori eradication rates. Our aim was to compare the efficacy of clarithromycin versus levofloxacin-based regimens for H. pylori treatment in naïve patients after the COVID-19 pandemic misuse of antibiotics. METHODS: A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were recruited. Patients were randomized to receive either clarithromycin, esomeprazole, and amoxicillin, or levofloxacin, esomeprazole, and amoxicillin. RESULTS: A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were included, 135 in each arm. In total, 19 patients in the clarithromycin group and 18 patients in the levofloxacin group stopped treatment after 2-4 days because of side effects or were lost for follow-up. Finally, 116 subjects in the clarithromycin group and 117 in the levofloxacin group were assessed. The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: group I, 55.56% and 64.66%; and Group II, 64.44% and 74.36% respectively (p = 0.11). CONCLUSION: As COVID-19 pandemic has moved forward fast, high resistance rates of H. pylori to both clarithromycin and levofloxacin were developed after less than two years from the start of the pandemic. Molecular & genetic testing is highly recommended to identify antimicrobial resistance patterns. Strategies to prevent antibiotic misuse in the treatment of COVID-19 are needed to prevent more antibiotic resistance. TRIAL REGISTRATION: The trial was registered on Clinicaltrials.gov NCT05035186. Date of registration is 2-09-2021.

Network meta-analysis of different dosages of esomeprazole and rabeprazole for the treatment of Helicobacter pylori.

BACKGROUND: The optimal dosage of new generation proton pump inhibitors (PPIs) in increasing cure rate of Helicobacter pylori (H. pylori) infection remains unclear. This network meta-analysis aimed to comprehensively evaluate the comparative efficacy and safety of different dosages of esomeprazole and rabeprazole in treating H. pylori infection. MATERIALS AND METHODS: We searched PubMed, Cochrane Central Registry for Controlled Trials (CENTRAL), and EMBASE for randomized controlled trials (RCTs) involving esomeprazole and rabeprazole with different dosages from their inception through 31 March, 2022. After data extraction and risk of bias assessment, network meta-analyses were conducted using STATA 14.0. We calculated the surface under the cumulative ranking (SUCRA) to rank all regimens. RESULTS: Thirteen studies including 14 reports were included. Six dosages including rabeprazole 10 mg (R10bid), 20 mg (R20bid), and 40 mg (R40bid) twice daily and esomeprazole 20 mg (E20bid) and 40 mg (E40bid) twice daily as well as 40 mg once daily (E40qd) were identified. Network meta-analysis suggested that R40bid ranked highest in the cure rate (83.8%), followed by E40bid (82.6%), E20bid (54.5%), R20bid (34.2%), R10bid (22.8%), and E40qd (22.0%); however, E40qd ranked highest in adverse events (91.1%), followed by R20bid (57.8), R10bid (57.6%), E20bid (38.9%), E40bid (34.2%), and R40bid (20.4%). Sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: Based on the available evidence, R40bid and E40bid might be the optimum dosage to increase the cure rate; however, E40qd was superior for adverse events. Nevertheless, future studies should validate the results from this network meta-analysis.

Intravenous metronidazole-, levofloxacin-containing triple therapy for treating patients with Helicobacter pylori-related active peptic ulcer complications: A pilot study.

OBJECTIVE: The aim of this pilot study was to evaluate the efficacy and safety of intravenous use esomeprazole, metronidazole, and/or levofloxacin in the treatment of Helicobacter pylori (H. pylori)-associated peptic ulcer complications. METHODS: Inpatients with peptic ulcer complications who were not able to take oral medicine were randomly assigned to three groups: triple therapy (esomeprazole, levofloxacin, metronidazole) and dual therapy (esomeprazole, levofloxacin/metronidazole) for 7 days. After intravenous treatment, all patients received open-label oral esomeprazole 20 mg bid for another 1 month. All subjects were followed up for gastroscopy at the seventh day of intravenous treatment to confirm the ulcer healing and 13 C-urea breath test to confirm successful H. pylori eradication 4-6 weeks after completion of oral esomeprazole therapy. RESULTS: The H. pylori eradication rate of both LEV-dual therapy (33.3%, 95% CI: 9.7%-70.0%) and MTZ-dual therapy (50%, 95% CI: 21.5%-78.5%) was significantly lower than that of triple therapy (95%, 95% CI: 71.1%-97.4%) (p = .003, .016). There were no significant differences in the adverse effects among all treatment groups, and the adverse effects were rare. CONCLUSIONS: The intravenous triple regimen, consisting of proton-pump inhibitor, metronidazole, and levofloxacin, could be considered in patients of H. pylori-associated peptic ulcer complications if oral medicine cannot be provided.

Health Care Cost Analysis of PPI or P-CAB-First Treatment in Patients With Gastroesophageal Reflux Disease.

GOALS: The aim was to examine actual health care cost in patients with gastroesophageal reflux disease (GERD) who were initiated on proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) as first-line therapy in Japanese real-world clinical settings. BACKGROUND: To date, cost-utility evaluation of acid-suppressants treatment in Japan has only been conducted by model analysis. STUDY: A cost utilization analysis was performed using a Japanese nationwide hospital-based claim database by extracting patients with GERD initiated on either PPI or P-CAB (242,102 pairs) and esomeprazole (EPZ) or P-CAB (241,825 pairs). Health care costs were compared in each comparison cohort with propensity-score matched pairs. The switching rates of initial acid-suppressants were also examined. RESULTS: Baseline characteristics were well-balanced after matching. The 3-year mean cumulative GERD-related and hospitalization costs per patient were ¥142,620 and ¥122,444 in PPI-first and P-CAB-first treatment groups, and ¥105,263 and ¥121,958 in EPZ-first and P-CAB-first treatment groups, respectively. Most hospitalization costs were non-GERD related in all the groups. The switching rates of PPI to P-CAB and P-CAB to PPI in 12 months were 7.5% and 20.2%, respectively. CONCLUSIONS: In this propensity-score matched analysis, health care cost was higher in patients with GERD initiated on PPI than in those initiated on P-CAB mainly owing to non-GERD-related hospitalization cost, whereas it was lower in those initiated on EPZ than in those initiated on P-CAB. When considering health care costs except hospitalization costs, PPI-first treatment was less expensive than P-CAB-first treatment. Low switching rate from PPI to P-CAB in the real-world practice may partially explain the discrepancy.

Cost-Effectiveness of Vonoprazan Compared With Proton Pump Inhibitors in Patients Taking Low-Dose Aspirin for Secondary Prevention of Cardiovascular Events in Japan.

BACKGROUND: Low-dose aspirin (LDA) is used to prevent recurrent cardiovascular (CV) events, but is associated with upper gastrointestinal (GI) bleeding; concomitant use of a proton pump inhibitor (PPI) reduces this risk. This study aimed to assess the cost-effectiveness of vonoprazan compared with PPIs (lansoprazole and esomeprazole) in patients taking LDA for secondary prevention of CV events.Methods and Results: A Markov simulation model was developed to predict the number of GI bleeding and acute CV events using 3 strategies (vonoprazan+LDA, esomeprazole+LDA, and lansoprazole+LDA), which were translated into quality-adjusted life-years (QALYs) and costs. Transition probabilities and utilities were derived from the results of published literature, and medical costs were based on the Japanese National Health Insurance fee table and claims databases in 2020. Outcomes were projected over 30 years starting at age 65 years and discounted at 2% annually. Expected costs with esomeprazole 20 mg, lansoprazole 15 mg and vonoprazan 10 mg were JPY 1,225,657, JPY 943,930, and JPY 1,059,510, respectively. The QALY gain for vonoprazan vs. esomeprazole was 0.35, thus vonoprazan was dominant against esomeprazole. The QALY gain for vonoprazan vs. lansoprazole was 0.29 and the incremental cost-effectiveness ratio (ICER) was JPY 398,551, thus, vonoprazan was more cost-effective than lansoprazole. CONCLUSIONS: Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

Randomized clinical trial: A double-blind, proof-of-concept, phase 2 study evaluating the efficacy and safety of vonoprazan 20 or 40 mg versus esomeprazole 40 mg in patients with symptomatic gastro-esophageal reflux disease and partial response to a healing dose of a proton-pump inhibitor.

BACKGROUND: Proton-pump inhibitors (PPIs) are cornerstone treatments for gastro-esophageal reflux disease (GERD); however, evidence suggests that most patients exhibit partial response to PPIs, suggesting the need for novel therapies that can provide an improved and sustained increase in gastric pH. AIMS: This study aimed to determine the effect of vonoprazan, a novel, orally active small-molecule potassium-competitive acid blocker, versus esomeprazole, a PPI, in preventing heartburn symptoms over a 4-week treatment period in patients with GERD and a partial response to esomeprazole treatment. METHODS: This randomized, double-blind, proof-of-concept, phase 2 clinical trial was conducted between 2016 and 2018 at 39 sites across Europe and designed to evaluate the efficacy and safety of vonoprazan 20 mg once daily (q.d.) and 40 mg q.d. versus esomeprazole 40 mg q.d. after 1:1:1 randomization of symptomatic patients with GERD and a partial response to a healing dose of esomeprazole. RESULTS: Overall, 256 eligible patients (female, 59.4%; mean age, 52.6 years) received vonoprazan 20 mg (n = 85), vonoprazan 40 mg (n = 85), or esomeprazole 40 mg (n = 86); mean (SD) percentages of heartburn-free 24-h periods during double-blind treatment were 36.7% (33.4%), 36.5% (35.6%), and 38.4% (34.8%), respectively, with no intergroup statistical significance. Vonoprazan exposure increased proportionally from the 20-mg to 40-mg dose (mean Cmax : 23.3 ng/ml to 47.1 ng/ml, respectively). Most treatment-emergent adverse events were mild, with no deaths reported. CONCLUSIONS: No statistically significant difference in efficacy and safety was observed among treatment groups, and vonoprazan was well tolerated. The trial is registered with the National Board of Health (EudraCT: 2015-001154-14) database.