Vonoprazan is superior to lansoprazole for healing of severe but not mild erosive esophagitis: A systematic review with meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Healing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60-70%). Vonoprazan, a potassium-competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta-analysis compares the efficacy and safety of vonoprazan 20 mg versus lansoprazole 30 mg daily in healing EE, specifically in those with LA Grade C/D. METHODS: We searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20 mg daily or lansoprazole 30 mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed-effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location. RESULTS: Four randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20 mg was superior to lansoprazole 30 mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169-1.433], Week 4 1.160 [1.059-1.270], and Week 8 1.175 [95% CI 1.107-1.247]), but was similar for mild EE at all weeks (P-interaction < 0.01). Vonoprazan 20 mg was more efficacious than lansoprazole 30 mg at Week 8 in Western versus Asian studies (P-interaction < 0.01). Any, serious, and drug-related treatment-emergent adverse events were comparable between groups. CONCLUSION: Vonoprazan 20 mg is superior to lansoprazole 30 mg for healing severe EE but not mild EE. Vonoprazan 20 mg daily has a similar safety profile to lansoprazole 30 mg daily.

Controlled release floating drug delivery system for proton pump inhibitors lansoprazole: In-vitro, In-vivo floating and pharmacokinetic evaluation.

Lansoprazole (LPZ) show poor bioavailability because of first pass effect and absorption factors. The floating delivery systems could reduce fluctuations in plasma drug concentration through maintaining desirable plasma drug concentration. The objective of present study was to enhance bioavailability despite first pass effect through continuous availability of drug from floating system. Gum tragacanth (GT) and itaconic acid (IA) based floating hydrogels (FH) were synthesized. Parameters optimized were; microwave radiation exposure time, pH, GT:IA ratio and concentration of the glutaraldehyde. Optimized FH were evaluated for entrapment efficiency (% EE), in-vitro release, FTIR, SEM, and in- vitro and in-vivo floating study. Finally, pharmacokinetic was evaluated in ulcer-induced SD rats. Grafting percentage, swelling ratio and %EE of LPZ was 115%, Ì´250% and 90%, respectively. Microwave radiation exposure time, pH of reaction medium, GT:IA ratios and cross linker concentration were 2 min, pH 5, ratios 2:1 and 0.02%, respectively. The optimized FH showed acceptable floating behavior. The X-ray images revealed that hydrogels remained floated over gastric contents up to 24 hours. The in-vitro release and pharmacokinetics revealed availability of LPZ upto to 24h in-vitro and in ulcer-induced SD rats, respectively. The present hydrogels based floating system of lansoprazole is capable to extend the gastric residence time upto 24 hours.

Acute kidney injury following the use of different proton pump inhibitor regimens: A real-world analysis of post-marketing surveillance data.

BACKGROUND AND AIM: Recent evidence has concerned acute kidney injury (AKI) after the proton pump inhibitor (PPI) application. There are few real-world studies to compare the occurrences, clinical features, and prognosis of AKI related to various PPI regimens. We aimed to evaluate and compare the links between different PPIs and AKI in a large population by investigating the Food and Drug Administration Adverse Event Reporting System (FAERS) until recently. METHODS: Disproportionality analysis and Bayesian analysis were used in data mining to screen the suspected AKI after different PPIs based on the FAERS from January 2004 to December 2019. The times to onset, fatality, and hospitalization rates of PPI-associated AKI were also investigated. RESULTS: We identified 19 522 PPI-associated AKIs, which appeared to influence more middle-aged patients than elderly ones (53.04% vs 33.94%). Women were more affected than men (55.42% vs 44.58%). Lansoprazole appeared a stronger AKI association than other PPIs, based on the highest reporting odds ratio (reporting odds ratio = 20.8, 95% confidence interval = 20.16, 21.46), proportional reporting ratio (proportional reporting ratio = 15.55, χ2  = 73 899.68), and empirical Bayes geometric mean (empirical Bayes geometric mean = 15.15, 95% confidence interval = 14.76). The median time to AKI onset was 446 (interquartile range [IQR] 16-2176) days after PPI administration. PPIs showed a significant difference in average time to AKI onset (P < 0.001), with the shortest of 9 (IQR 3-25) days for rabeprazole and the longest of 1221 (IQR 96.5-2620) days for esomeprazole. PPI-associated AKI generally led to a 5.69% fatality rate and an 8.94% hospitalization rate. The highest death rate occurred in rabeprazole (15.35%). CONCLUSIONS: Based on the FAERS database, we profiled AKI related to various PPIs with more details in occurrences, clinical characteristics, and prognosis. Concern should be paid for PPIs when applied to patients with a tendency for AKI.

Gastric mucosal changes, and sex differences therein, after Helicobacter pylori eradication: A long-term prospective follow-up study.

BACKGROUND AND AIM: Improvement of atrophic gastritis and intestinal metaplasia (IM) is considered to reduce the gastric cancer risk, but whether it can be achieved by H. pylori eradication (HPE) remains controversial. To evaluate the effect of HPE, we observed the gastric mucosa for up to17 years after HPE and sex differences in gastric mucosa. METHODS: In total, 172 patients (94 males, 78 females) with HPE were enrolled. Annual histological evaluations were performed for up to 17 years. The grades of mononuclear cells, neutrophils, atrophy, IM in the antrum and corpus were evaluated using the updated Sydney system. RESULTS: Relative to the pre-HPE period, atrophy had improved significantly 1 year after HPE in the antrum (1.50 ± 0.75 vs. 1.21 ± 1.25, P < 0.01) and corpus (0.59 ± 0.75 vs. 0.18 ± 0.52, P < 0.05). IM showed no significant change during 17 years after HPE at either biopsy site. Atrophy scores did not differ significantly between males and females. IM scores were significantly higher in males than in females before eradication (antrum, 0.67 ± 0.94 vs. 0.44 ± 0.77, P = 0.003, corpus, 0.20 ± 0.62 vs. 0.047 ± 0.21, P = 0.0027) and at most observation timepoints. CONCLUSIONS: During 17 years after HPE, atrophy, but not IM, improved significantly at the greater curvatures of the antrum and corpus. IM was significantly more severe in males than in females. Careful follow-up after HPE based on sex differences in gastric mucosal characteristics is important.

In vitro evaluation of enteral tube administration of lansoprazole orally disintegrating tablets.

Lansoprazole orally disintegrating tablets (ODTs) can be administered orally or through a nasogastric (NG) tube for patients who are unable to swallow. In addition, off-label administration through gastrostomy (G) or jejunal (J) tubes has been reported. The purpose of this study was to develop in vitro methods to assess the risk of clogging during administration of two lansoprazole ODTs through enteral feeding tubes. Feeding tubes of various compositions and geometries were selected for testing. Disintegration, sedimentation, percent recovery, acid phase dissolution testing, and particle size distribution measurements were performed. The results indicated that G tubes had the greatest risk of clogging compared to NG and J tubes. In addition, larger particles and an increased amount of insoluble excipients observed in Product B resulted in more irreversible enteral tube clogging than compared to Product A. The geometry and design of the tube also had an impact on the amount of lansoprazole recovered after enteral tube administration. Lansoprazole ODTs demonstrated acid resistance stability regardless of the water used for suspension. The in vitro methods discussed in this work could be used to evaluate in vitro equivalence and to assess the risk of delivering a drug product through an enteral feeding tube.

Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis.

OBJECTIVE: To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO). DESIGN: In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively. CONCLUSION: Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms. TRIAL REGISTRATION NUMBER: NCT02388724.

Comparison of the efficiency of two different proton pump inhibitor formula in treatment of patients with atypical gastroesophageal reflux disease: a prospective randomized study.

BACKGROUND AND AIM: The prospective, open-label, randomized study aims to compare the efficacy of lansoprazole, a fast orally disintegrating proton pump inhibitor (PPI), and dexlansoprazole, a dual delayed release PPI, in patients with atypical symptoms of gastroesophageal reflux disease (GERD). METHODS: Patients with atypical GERD symptoms with a total reflux symptom index score > 10 were eligible for enrollment. From February 2018 to December 2019, 232 subjects were randomly assigned (1:1 ratio) to receive oral lansoprazole, Takepron OD 30 mg, once daily before breakfast or oral dexlansoprazole, Dexilant 60 mg, once daily before breakfast for 8 weeks. The primary end-point is to compare the symptoms response rate after an 8-week PPI therapy between the two groups. RESULTS: There were 232 study subjects enrolling in this study. After the 8-week PPI therapy, dexlansoprazole-treated group had a significantly higher response rate than lansoprazole-treated group in cough (76.5% vs 38.0%) and globus (69.7% vs 30.8%) (P all < 0.05 by intention-to-treat). Multivariate logistic regression analysis showed that the use of dexlansoprazole, presence of dyslipidemia, and typical GERD symptoms (acid reflux and heartburn) were predictors for symptom response for cough; the use of dexlansoprazole and presence of erosive esophagitis were predictors for symptom response for globus (P all < 0.05). No predictor for therapy response to hoarseness was noted. CONCLUSIONS: There is a higher response rate for cough and globus symptoms in patients with atypical GERD after the 8-week PPI therapy with dexlansoprazole rather than lansoprazole.

Helicobacter pylori Eradication Regressed Gastric Hyperplastic Polyp: A Randomized Controlled Trial.

BACKGROUND: Helicobacter pylori infection and hyperplastic polyp are known to have strong connections, but there are not enough randomized controlled trial data. AIMS: To evaluate the effect of H. pylori eradication on gastric hyperplastic polyp. METHOD: This is an open-labeled, single-center, randomized controlled trial. Patients with hyperplastic polyp and current infection of H. pylori were randomly assigned to eradication or non-eradication groups. All participants underwent follow-up endoscopy to investigate the regression of gastric polyps. Gastric polyp regression was defined as the disappearance of polyps or a reduction of more than 50% in size. RESULTS: Thirty-two patients were randomized to eradication (n = 17) and non-eradication groups (n = 15). Final included patients were 14 in eradication group and 13 in non-eradication group. All patients showed polyp regression in eradication group, whereas no regression was observed in non-eradication group (P < 0.001). Disappearance of polyp (n = 7) and decrease in size (n = 7) were observed in eradication group. In non-eradication group, no change (n = 5), increase of size (n = 5), and increase of number (n = 3) were observed. Mean regression time was 6.8 months, and disappearance time was 9.8 months. In non-eradication group, hyperglycemia was noted in 50% of progression group but not noted in no change group (P = 0.057). CONCLUSIONS: H. pylori eradication induced regression of hyperplastic polyp, and persistent H. pylori infection was related to progression of gastric polyp. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03065868.

The proton pump inhibitor, lansoprazole, prevents the development of non-traumatic osteonecrosis of the femoral head: an experimental and prospective clinical trial.

BACKGROUND: An effective prevention strategy for osteonecrosis of the femoral head (ONFH) has yet to be established. We previously reported that the innate immune system via the toll-like receptor (TLR) response induced by corticosteroids leads to the development of ONFH and that repression of IRF7 activity by an inhibitor could interfere with the development of ONFH while maintaining the therapeutic effect of the corticosteroids. OBJECTIVE: In the present study, we hypothesize that lansoprazole has the potential to suppress IRF7 activity and prevent corticosteroid-induced ONFH in rats. Furthermore, we conducted a preliminary clinical trial to prevent corticosteroid-induced ONFH in autoimmune disease patients. METHODS: Male Wistar rats were randomly divided into four groups. On Day 1, each rat was injected with TLR4 ligand (LPS) or TLR7 ligand (imiquimod), followed by methylprednisolone with or without lansoprazole on Day 2. They were killed at 1 or 14 days after the last injection.We prospectively recruited 30 patients requiring primary high-dose corticosteroid treatment for immune diseases. All patients were administered lansoprazole, starting the night before corticosteroid treatment began. MRI was performed before corticosteroid treatment, and at 4, 12 and 24 weeks afterward. RESULTS: In rats, co-treatment of lansoprazole with corticosteroids significantly repressed both IRF7 activity and the development of ONFH. Moreover, in the human patients, the incidence of ONFH was significantly decreased from 53.4 to 13.3%. CONCLUSIONS: Although the present study is preliminary, the results show that co-treatment of lansoprazole with corticosteroids prevents ONFH development. Lansoprazole may be both safe and effective in preventing osteonecrosis of the femoral head in patients needing corticosteroid treatment.

PRIMMO study protocol: a phase II study combining PD-1 blockade, radiation and immunomodulation to tackle cervical and uterine cancer.

BACKGROUND: Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade in gynecological cancers showed objective responses in 13-17% of patients. This could be due to immunosuppressive effects exerted by gynecological tumors on the microenvironment and an altered tumor vasculature. In other malignancies, combining checkpoint blockade with radiation delivers benefit that is believed to be due to the abscopal effect. Addition of immune modulation agents has also shown to enhance immune checkpoint blockade efficacy. Therefore we designed a regimen consisting of PD-1 blockade combined with radiation, and different immune/environmental-targeting compounds: repurposed drugs, metronomic chemotherapy and a food supplement. We hypothesize that these will synergistically modulate the tumor microenvironment and induce and sustain an anti-tumor immune response, resulting in tumor regression. METHODS: PRIMMO is a multi-center, open-label, non-randomized, 3-cohort phase 2 study with safety run-in in patients with recurrent/refractory cervical carcinoma, endometrial carcinoma or uterine sarcoma. Treatment consists of daily intake of vitamin D, lansoprazole, aspirin, cyclophosphamide and curcumin, starting 2 weeks before the first pembrolizumab dose. Pembrolizumab is administered 3-weekly for a total of 6 cycles. Radiation (3 × 8 Gy) is given on days 1, 3 and 5 of the first pembrolizumab dose. The safety run-in consists of 6 patients. In total, 18 and 25 evaluable patients for cervical and endometrial carcinoma respectively are foreseen to enroll. No sample size is determined for uterine sarcoma due to its rarity. The primary objective is objective response rate at week 26 according to immune-related response criteria. Secondary objectives include safety, objective response rate at week 26 according to RECIST v1.1, best overall response, progression-free survival, overall survival and quality of life. Exploratory, translational research aims to evaluate immune biomarkers, extracellular vesicles, cell death biomarkers and the gut microbiome. DISCUSSION: In this study, a combination of PD-1 blockade, radiation and immune/environmental-targeting compounds is tested, aiming to tackle the tumor microenvironment and induce anti-tumor immunity. Translational research is performed to discover biomarkers related to the mode of action of the combination. TRIAL REGISTRATION: EU Clinical Trials Register: EudraCT 2016-001569-97 , registered on 19-6-2017. Clinicaltrials.gov: NCT03192059 , registered on 19-6-2017.

Twice daily short-message-based re-education could improve Helicobacter pylori eradication rate in young population: A prospective randomized controlled study.

BACKGROUND: To investigate the effects of twice daily short-message-based re-education (SMRE) before taking medicine for Helicobacter pylori (H pylori) eradication. MATERIALS AND METHODS: Treatment-naive patients with H pylori infection were prescribed 14-day quadruple regimen consisting of lansoprazole 30 mg, colloidal bismuth pectin 200 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily. Patients were randomly allocated to SMRE group or control group. Patients in control group received oral and written instructions at outpatient clinic. In contrast, patients in the SMRE group received extra short messages including dosage and time of administration twice daily. Successful H pylori eradication was assessed using the 13 C-urea breath test 6 weeks after treatment. The compliance, adverse events, and patient satisfaction were also analyzed. RESULTS: A total of 310 patients were enrolled in the intention-to-treat (ITT) and 283 in the per-protocol (PP) analysis. For young patients, the eradication rates were significantly higher in SMRE group than those in control group in PP analysis (88.6% vs 71.2%, P = 0.036), while for patients of all age groups, the eradication rate improvements were not statistically significant. The eradication rates in SMRE group and control group were 74.2% and 67.7% (P = 0.211) in ITT analysis and 82.1% and 73.4% (P = 0.078) in PP analysis, respectively. The compliance in SMRE group was significantly better than that in control group (84.8% vs 72.8%, P = 0.011). CONCLUSIONS: Twice daily SMRE could improve the eradication rate in young population, as well as the compliance with treatment during H pylori eradication.

Randomized trial of vonoprazan-based versus proton-pump inhibitor-based third-line triple therapy with sitafloxacin for Helicobacter pylori.

BACKGROUND AND AIM: This was a prospective, randomized trial of the efficacy of vonoprazan-based and proton-pump inhibitor-based 7-day triple regimens with amoxicillin and sitafloxacin as a third-line therapy for eradicating Helicobacter pylori after failure of clarithromycin-based and metronidazole-based first-line and second-line therapy. METHODS: We enrolled 63 patients positive for H. pylori in whom first-line and second-line regimens for eradicating failed. Patients were randomized to the V-AS group (vonoprazan 20-mg bid, amoxicillin 750-mg bid, and sitafloxacin 100-mg bid for 7 days) or PPI-AS group (esomeprazole 20-mg bid, rabeprazole 10-mg bid, or lansoprazole 30-mg bid; amoxicillin 750-mg bid; and sitafloxacin 100-mg bid for 7 days). We assessed the outcome of eradication therapy using the 13 C-urea breath test. We evaluated safety using patient questionnaires. This study was registered in the UMIN Clinical Trials Registry (UMIN000016336). RESULTS: The intention-to-treat and per-protocol eradication rates of V-AS were 75.8% (95% confidence interval [CI]: 57.7-88.9%) and 83.3% (95% CI: 65.3-94.4%), respectively. The respective eradication rates of PPI-AS were 53.3% (95% CI: 34.3-71.7%) and 57.1% (95% CI: 37.2-75.5%). In per-protocol analyses, the eradication rate of the V-AS group was significantly higher than that of the PPI-AS group (P = 0.043); however, no significant differences were observed in intention-to-treat analyses (P = 0.071). Questionnaire scores did not differ significantly between the groups. CONCLUSIONS: The findings suggest that 7-day triple therapy with vonoprazan, amoxicillin, and sitafloxacin is more effective than proton-pump inhibitor, amoxicillin, and sitafloxacin as a third-line regimen for eradicating H. pylori.

Intraluminal therapy for Helicobacter pylori infection.

BACKGROUND AND AIM: Several strategies have been proposed to increase the eradication rate of Helicobacter pylori. However, the widespread increasing resistance rates to current multiple-dose oral antibiotic therapies call for alternative therapeutic approaches. We aim to develop a novel intraluminal therapy for H. pylori infection (ILTHPI). METHODS: From April 2017 to December 2017, 100 H. pylori-infected treatment-naïve patients with upper abdominal pain or discomfort underwent endoscopic examinations and concomitant ILTHPI, which comprised the control of intragastric pH, the irrigation of gastric mucosal surface with a mucolytic agent, and the application of single-dose medicaments containing antibiotic powders. The safety profiles while conducting ILTHPI and adverse events after ILTHPI were evaluated. The success of eradication was assessed based on the result of the 13 C-urea breath test 6 weeks after ILTHPI. In addition, a patient with successful ILTHPI was reconfirmed by a negative H. pylori stool antigen test four to 6 months after ILTHPI to exclude short-term recurrence. RESULTS: All the 100 enrolled patients completed the ILTHPI with good safety profiles and mild adverse events (6%). Five patients dropped out, and 51 of 95 patients (53.7%) achieved successful eradication immediately after endoscopic examinations. All 51 patients revealed negative stool H. pylori antigen tests four to 6 months after successful ILTHPI. No short-term recurrence was observed. CONCLUSIONS: We have developed a novel therapeutic approach. With the ILTHPI, H. pylori can be eradicated immediately by administrating a single-dose regimen while conducting an endoscopic examination. CLINICAL TRIALS NUMBER: NCT03124420.

The status of proton pump inhibitor use: a prescription survey of 45 hospitals in China.

BACKGROUND: proton pump inhibitors (PPI) have been widely used in the clinic but inappropriate prescribing has also increased dramatically. OBJECTIVE: to describe the prescribing patterns and assess the appropriateness of the prescribed PPI use in 45 hospitals in China. MATERIALS AND METHODS: PPI prescriptions for non-hospitalized patients were collected from hospitals in Beijing, Chengdu, Guangzhou and Hangzhou of China over a 40-day period in 2016. These data were analyzed using the prescription number, proportion and economic indicators (defined daily dose system [DDD], defined daily cost [DDC] and drug utilization index [DUI]). The evaluation criteria of PPI use was based on Martindale: The Complete Drug Reference, New Materia Medica and drug instructions. RESULTS: in total, 357,687 prescriptions using oral PPI and 38,216 prescriptions using injectable PPI were assessed. The average age of PPI users was 53 years. The most commonly used oral PPI was rabeprazole, while the most common injectable PPI was pantoprazole. The DDD of oral rabeprazole and DDC of injectable rabeprazole were the highest. Meanwhile, only the DUI values of oral rabeprazole, lansoprazole and ilaprazole were less than 1.0. The clinical diagnosis of some users included well identified risky comorbidities such as kidney disease (2.9%). Furthermore, between 32.6% and 56.8% of the PPI prescriptions were used for inappropriate indications. CONCLUSION: this survey demonstrated that PPI use was accompanied by unapproved indications and excessive dosages. Comprehensive measures are urgently needed to improve PPI use and reduce unnecessary drug costs.

Proton Pump Inhibitors Increase Risk for Hepatic Encephalopathy in Patients With Cirrhosis in A Population Study.

BACKGROUND & AIMS: Hepatic encephalopathy (HE) is a serious complication of cirrhosis and is associated with gut dysbiosis. Proton pump inhibitors (PPIs), frequently prescribed to patients with cirrhosis, can contribute to small-bowel bacterial overgrowth. We investigated whether PPI predisposes patients with cirrhosis to HE using a large database of patients. METHODS: We performed a case-control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000), followed up longitudinally from 1998 through 2011. Patients with cirrhosis and an occurrence of HE (n = 1166) were selected as the case cohort and matched to patients without HE (1:1, controls) for sex, enrollment time, end point time, follow-up period, and advanced cirrhosis. Information on prescribed drugs, drug dosage, supply days, and numbers of dispensed pills was extracted from the Taiwan National Health Insurance database. PPI use was defined as more than 30 cumulative defined daily doses (cDDDs); PPI nonuse was defined as 30 cDDDs or fewer. We performed logistic regression analyses to estimate the association between PPI use and the occurrence of HE. RESULTS: Among patients with cirrhosis and an occurrence of HE, 38% (n = 445) had a history of PPI use before HE occurrence. We observed a relationship between dose of PPI taken and HE risk. The confounder-adjusted odd ratios were 1.41 (95% confidence interval [CI], 1.09-1.84), 1.51 (95% CI, 1.11-2.06), and 3.01 (95% CI, 1.78-5.10) for patients with 30-120 cDDDs, 120-365 cDDDs, and more than 365 cDDDs, respectively, compared with PPI nonusers. All categories of PPIs, except rabeprazole, were associated with an increased risk of HE. CONCLUSIONS: Based on an analysis of data from Taiwan National Health Insurance beneficiaries, we found that use of PPIs in patients with cirrhosis increases the risk for HE; risk increases with dose. It therefore is important for health care providers to carefully consider prolonged PPI use by patients with cirrhosis.

Short-term efficacy of potassium-competitive acid blocker following gastric endoscopic submucosal dissection: a propensity score analysis.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a promising method for the resection of superficial gastric neoplasms. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that is currently considered as a potential alternative to proton pump inhibitors (PPIs) for the treatment of acid-related diseases. However, the utility of vonoprazan in ESD-related ulcers is unclear. Therefore, we compared the short-term efficacies of vonoprazan and the PPI lansoprazole in ESD-related ulcer healing during the first two weeks following intervention. METHODS: This study included 115 superficial gastric neoplasms that were treated by ESD at Hiraka General Hospital between April 2015 and January 2017. Patients treated with P-CAB (20 mg vonoprazan, n = 62) or PPI (30 mg lansoprazole, n = 53) were compared using propensity-score matching analysis. Primary outcome was rate of ulcer reduction at two weeks after ESD. Secondary outcomes were coverage ratio of ulcer base by granulation tissue and incidence of postoperative bleeding. RESULTS: The rate of ulcer reduction was significantly higher (median [range], 80.6% [67.6%-94.5%] vs. 62.7% [33.4%-85.2%]; p < .0001) and coverage ratio of the ulcer base by granulation tissue was significantly accelerated (median [range], 84.1% [67.7%-95.3%] vs. 61.9% [12.1%-90.1%]; P < 0.0001) in the P-CAB group compared with the PPI group. Postoperative bleeding was not observed in either group. CONCLUSIONS: P-CAB achieved rapid artificial ulcer healing with promotion of granulation tissue formation. However, conventional PPI with initial intravenous infusion might be sufficient for prevention of postoperative bleeding following gastric ESD.

Empirical treatment of outpatients with gastroesophageal reflux disease with proton pump inhibitors: A survey of Chinese patients (the ENLIGHT Study).

BACKGROUND AND AIM: Empirical proton pump inhibitor (PPI) treatment is recommended as a diagnostic indicator for gastroesophageal reflux disease (GERD) and as a therapy for symptomatic control, with responses generally seen within 4 weeks. However, there are no real-world data assessing the effectiveness of short-term empirical treatment with PPIs in patients with GERD in China. METHODS: The ENLIGHT study was a multicenter, prospective, observational study conducted in China. The primary outcome was the overall response rate after 4 weeks' empirical treatment with PPIs. Adult patients aged between 18 and 65 years of age, with a gastroesophageal reflux disease questionnaire score of ≥ 8, prescribed empirical PPI treatment by their physicians and with no planned endoscopy were eligible to participate. Statistical analyses were primarily descriptive. RESULTS: Overall, 987 patients were eligible to participate and were included in the full analysis set (FAS); 707 patients were included in the per protocol set. In the FAS, esomeprazole was received by 57.1% of patients and was the most commonly used PPI. After 4-week treatment, 71.1% (95% confidence interval [CI], 67.9% to 74.2%) of patients were considered responders to PPI. The response rate at the end of 2-week PPI treatment reached 57.0% (95% CI, 52.5% to 61.7%). The median time to response was 13 days (95% CI, 12 to 15). Response rates at 2 and 4 weeks of the per protocol set were similar to those of the FAS. CONCLUSIONS: Short-term empirical PPI treatment can provide an effective relief of GERD symptoms in most Chinese patients in real-world practice.

Ten-day high-dose proton pump inhibitor triple therapy versus sequential therapy for Helicobacter pylori eradication.

BACKGROUND AND AIM: Eradication rates of Helicobacter pylori following standard triple therapy are declining worldwide, but high-dose proton pump inhibitor-based triple therapy (HD-PPI-TT) and sequential therapy (ST) have demonstrated higher cure rates. We aimed to compare the efficacy and tolerability of HD-PPI-TT and ST in H. pylori-associated functional dyspepsia (FD). METHODS: One hundred and twenty H. pylori-associated functional dyspepsia patients were randomized to receive 10-day HD-PPI-TT (60 mg lansoprazole/500 mg clarithromycin/1 g amoxicillin, each administered twice daily for 10 days) or 10-day ST (30 mg lansoprazole/1 g amoxicillin, each administered twice daily for 5 days followed by 30 mg lansoprazole/500 mg clarithromycin/400 mg metronidazole, each administered twice daily for 5 days). H. pylori status was determined in post-treatment week 4 by 14 C-urea breath test. Eradication and antibiotic resistance rates, dyspeptic symptoms, drug compliance, and adverse effects were compared. RESULTS: Intention-to-treat eradication rates were similar in the ST and HD-PPI-TT groups (85% vs. 80%; P = 0.47). However, the eradication rate was significantly higher following ST compared with HD-PPI-TT in per protocol analysis (94.4% vs. 81.4%; P = 0.035). ST achieved higher cure rates than HD-PPI-TT in clarithromycin-resistant H. pylori strains (100% vs. 33.3%; P = 0.02). Treatment compliance was similar in the HD-PPI-TT and ST groups, although nausea and dizziness were more common in the ST group. CONCLUSIONS: Sequential therapy achieved better H. pylori eradication than HD-PPI-TT in patients with FD. However, the eradication rate for ST fell from 94.4% in per protocol to 85% in intention-to-treat analysis. Adverse effects might result in poorer compliance and compromise actual ST efficacy (ClinicalTrials.gov: NCT01888237).

Proton Pump Inhibitors Increase the Susceptibility of Mice to Oral Infection with Enteropathogenic Bacteria.

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the most frequently prescribed medications. Side effects including an increased risk of intestinal infections have been reported. It is assumed that PPIs can increase susceptibility to enteropathogens; however, the underlying mechanisms are unknown. Here in this study, we explored whether Lansoprazole (Laz), one of the PPIs, increases the susceptibility to enteropathogens, and further investigated the mechanism of it. METHODS: Mice were administered Laz intraperitoneally once daily and orally infected with Citrobacter rodentium (C. rodentium). The establishment of intestinal infection was assessed by histology and inflammatory cytokine expression levels measured by quantitative PCR. To test whether Laz changes the intestinal environment to influence the susceptibility, intestinal pH, microbiota, metabolites and immune cell distributions were evaluated via pH measurement, 16S rRNA gene sequencing, metabolome, and flow cytometry analyses after Laz administration. RESULTS: Colitis was induced with less C. rodentium in Laz-treated mice as compared with the controls. We found that increased numbers of C. rodentium could reach the cecum following Laz administration. Laz increased pH in the stomach but not in the intestines. It induced dysbiosis and changed the metabolite content of the small intestine. However, these changes did not lead to alterations of immune cell distribution. CONCLUSIONS: Laz raised susceptibility to C. rodentium as increased numbers of the pathogen reach the site of infection. Our results suggest that it was due to increased stomach pH which allowed more peroral enteropathogens to pass the stomach, but not because of changes of intestinal environment.

Comparison of oral and intravenous lansoprazole for the prevention of bleeding from artificial ulcers after endoscopic submucosal dissection for gastric tumors: a prospective randomized phase II study (KDOG 0802).

BACKGROUND: Very few studies have evaluated the effectiveness of oral proton-pump inhibitors for the prevention of bleeding after endoscopic submucosal dissection (ESD) for gastric tumors. The aim of our study was to establish the non-inferiority of lansoprazole orally disintegrating (OD) tablets to intravenous lansoprazole for the prevention of bleeding from artificial ulcers after ESD. PATIENTS AND METHODS: Consecutive patients who underwent ESD for gastric tumors were randomly assigned to receive lansoprazole OD tablets (OD group) or intravenous lansoprazole (IV group). In the OD group, lansoprazole OD tablets (30 mg) were given orally once daily for 8 weeks (56 days), starting on the day before ESD. In the IV group, lansoprazole (30 mg) was given as a continuous intravenous infusion twice daily for 3 days, starting on the day before ESD, and lansoprazole OD tablets (30 mg) were given orally once daily on days 4-56. The primary endpoint was the incidence of bleeding events within 8 weeks after ESD. RESULTS: Among 310 enrolled patients, 304 patients (152 in the OD group and 152 in the IV group) were included in the analysis. Endoscopic hemostasis was performed in 38 patients (19 in the OD group and 19 in the IV group). The incidence of bleeding events within 8 weeks after ESD did not differ significantly between the groups (p = 0.487). Endoscopic hemostasis was performed at second-look endoscopy in 17 patients (11.2%) in the OD group and 19 patients (12.5%) in the IV group (difference, 1.3 percentage points; 90% confidence interval, - 4.8-7.4%; non-inferiority, p < 0.001). CONCLUSIONS: The effectiveness of lansoprazole OD tablets for the prevention of bleeding from artificial ulcers after ESD was similar to that of intravenous lansoprazole. Lansoprazole OD tablets are thus considered a treatment option in patients who undergo ESD.