Comparison of Helicobacter pylori eradication rates between 7 and 14 days of tailored therapy according to clarithromycin resistance test: A randomized, multicenter, non-inferiority study.

BACKGROUND: Recently, a simple tailored therapy based on clarithromycin resistance has been implemented as Helicobacter pylori (H. pylori) eradication therapy. Nonetheless, despite the tailored therapy and frequent adverse events, studies on treatment period are lacking. This study aimed to compare the H. pylori eradication rates of 7-day and 14-day tailored therapy regimens according to clarithromycin resistance. MATERIALS AND METHODS: This multicenter, prospective, randomized, noninferiority trial enrolled H. pylori-positive patients who were randomly assigned to 7-day and 14-day regimen groups, depending on the presence or absence of clarithromycin resistance by 23S rRNA gene point mutations. Standard triple therapy (STT) (20 mg rabeprazole, 1 g amoxicillin, and 500 mg clarithromycin twice daily) or bismuth quadruple therapy (BQT) (20 mg rabeprazole twice daily, 500 mg metronidazole thrice daily, 120 mg bismuth four times daily, and 500 mg tetracycline four times daily) was assigned by clarithromycin resistance. Eradication rates and adverse events were evaluated. RESULTS: A total of 314 and 278 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively; however, 31 patients were lost to follow-up, whereas five patients violated the protocol. Both the 7-day and 14-day regimens showed similar eradication rates in the ITT (7-day vs. 14-day: 78.3% vs. 78.3%, p > 0.99) and PP (87.9% vs. 89.1%, p = 0.851) analyses. Non-inferiority was confirmed (p < 0.025). A subgroup analysis according to clarithromycin resistance (clarithromycin resistance rate: 28.7%) revealed no significant difference in eradication rates between the 7-day and 14-day STT (90.0% vs. 90.1%, p > 0.99) and BQT (82.5% vs. 86.5%, p = 0.757). Furthermore, adverse events did not significantly differ between the two groups. CONCLUSIONS: The 7-day triple and quadruple therapy according to clarithromycin resistance showed similar eradication rates, as compared to the 14-day therapy.

Amoxicillin, gemifloxacin and rabeprazole, as first-line Helicobacter pylori therapy in clinical practice: A pilot study.

Success in eradication of H. pylori is decreasing due to increasing resistant strains. In particular, side-effects due to 4-agent treatment multiple drug use are observed and treatment compliance decreases. The aim of this study was to evaluate the efficacy, reliability, and side-effect profile of the combination of amoxicillin and rabeprazole with gemifloxacin, which is a new generation quinolone, in the treatment of H. pylori infection. This study was conducted on 71 naive patients who received H. pylori eradication. All the patients were administered treatment of Amoxicillin (1000 mg twice a day) + Gemifloxacin (320 mg once a day) + rabeprazole (20 mg twice a day) for 7 days. Drug compliance and treatment tolerance were evaluated after finishing the treatment. At 1 month after the end of the treatment, H. pylori eradication was evaluated in all the patients by examining H. pylori antigen in the feces. In the evaluation after treatment, H. pylori eradication was obtained in 63 (88.7%) patients and eradication was not obtained in 8 (11.3%) patients. The treatment was not completed by 2 patients because of side-effects and noncompliance, so after exclusion of these 2 patients, successful H. pylori eradication was obtained in 63 (91.3%) of 69 patients who completed the treatment. Side-effects were seen in a total of 9 (12.7%) patients. Diarrhea, bloating, abdominal pain, and nausea-vomiting were seen in some patients, but no reflux, constipation, skin rash, listlessness-fatigue, headache, dizziness, palpitations, dry mouth, or weight loss was seen in any patient. In regions with high resistance to clarithromycin and metronidazole in particular, the combination of gemifloxacin with amoxicillin and rabeprazole can be considered for use in first-stage treatment as both the efficacy and tolerability are high.

Clinical efficacy of Yukgunja-tang combined with a proton pump inhibitor for refractory gastroesophageal reflux disease: study protocol for randomized, double-blind, double-dummy clinical trial.

BACKGROUND: Yukgunja-tang (YGJ) is an herbal prescription used to treat the symptoms of gastroesophageal reflux disease (GERD). Although many preclinical and clinical studies on YGJ have been conducted on GERD, there is a lack of evidence from blinded studies to exclude placebo effects. Therefore, this protocol proposes a clinical trial that is single-centered, randomized, double-blinded, double-dummy to objectively evaluate the efficacy and safety of co-administered YGJ and rabeprazole (RPZ) in patients with GERD previously treated with proton pump inhibitors (PPIs) and still experiencing symptoms. METHODS: A total of 86 participants with refractory GERD (rGERD) will be randomized in a 1:1 ratio to the treatment [YGJ and RPZ (10 mg/d)] and control groups [double-dose RPZ (20 mg/d)] for 4 weeks of treatment (weeks 0-4) followed by 4 weeks of follow-up (weeks 4-8). The Frequency Scale for the Symptoms of GERD will be analyzed for the primary endpoint. Reflux Disease Questionnaire, Reflux Symptom Score, GERD-Health Related Quality of Life, Overall Treatment Evaluation, Spleen Qi Deficiency Questionnaire, Damum Questionnaire, and dyspepsia Visual Analogue Scale will be used to evaluate treatment effects on GERD related symptoms and quality of life and to compare treatment effects by subgroups. Safety tests will be analyzed by investigating adverse events. DISCUSSION: This clinical trial will be the first rigorous double-blind, double-dummy, placebo-controlled study to precisely evaluate the efficacy and safety of the combination of YGJ and PPIs in the treatment of rGERD. The results of this study will provide a reliable clinical basis for selecting botanical drug treatments for patients with rGERD. TRIAL REGISTRATION: Clinical Research Information Service (registration number: KCT0008600, July 13, 2023, https://cris.nih.go.kr ).

[Comparison of the effectiveness of rabeprazole original and generic products in the monotherapy of gastroesophageal reflux disease].

AIM: To compare the effectiveness of rabeprazole original and generic products in the treatment of gastroesophageal reflux disease (GERD) using impedance-pH monitoring. MATERIALS AND METHODS: Patients (n=35) diagnosed with GERD were divided into two groups. Group 1 patients (n=17, 45.2±1.7 years) received the rabeprazole original product (Pariet) 20 mg/day; Group 2 patients (n=18, 48.1±1.9 years) received 20 mg/day of a generic product. On Day 10 of therapy, all patients underwent 24-hour esophagus impedance-pH monitoring (Ohmega, Medical Measurement Systems, the Netherlands). The percentage of time with pH<4 in the esophagus, the total number and number of acidic, slightly acidic and slightly alkaline gastroesophageal refluxes (GERs), the latency period, and the duration of rabeprazole action were analyzed. The clinical efficacy of the drug was assessed using the GerdQ questionnaire. Statistical data were processed using Microsoft Office 2010 (Excel) and Biostat 2000 software packages. RESULTS: No significant differences were noted between the two groups of patients by gender, age, body mass index, smoking frequency, and GERD type (p>0.05). The average duration of action of the rabeprazole original product was significantly higher than that of the generics (13.2±0.6 and 8.8±0.7 h, respectively, p<0.05). In the rabeprazole original product group, compared to the generics group, the following values were lower: total GERs - 47.0 [43.3; 60.0] and 71.8 [54.3; 95.0], respectively, p<0.05; percentage of time with intraesophageal pH<4 - 1.8 [0.5; 2.3] and 2.1 [0.3; 6.8], respectively, p<0.05; the number of acidic GERs - 4.7 [2.2; 12.0] and 23.3 [12.6; 32.0], respectively, p<0.05. The total GerdQ questionnaire score in Group 1 was significantly lower than in Group 2 (5.4±0.1 vs 6.9±0.4, respectively; p>0.05). CONCLUSION: In treating GERD with the rabeprazole original product compared to generics, a significantly longer duration of acid production suppression, a more pronounced decrease in esophageal acidification, and a more statistically significant clinical improvement were observed.

Repurposing of rabeprazole as an anti-Trypanosoma cruzi drug that targets cellular triosephosphate isomerase.

Trypanosoma cruzi is the causative agent of American trypanosomiasis, which mainly affects populations in Latin America. Benznidazole is used to control the disease, with severe effects in patients receiving this chemotherapy. Previous studies have demonstrated the inhibition of triosephosphate isomerase from T. cruzi, but cellular enzyme inhibition has yet to be established. This study demonstrates that rabeprazole inhibits both cell viability and triosephosphate isomerase activity in T. cruzi epimastigotes. Our results show that rabeprazole has an IC50 of 0.4 µM, which is 14.5 times more effective than benznidazole. Additionally, we observed increased levels of methyl-glyoxal and advanced glycation end products after the inhibition of cellular triosephosphate isomerase by rabeprazole. Finally, we demonstrate that the inactivation mechanisms of rabeprazole on triosephosphate isomerase of T. cruzi can be achieved through the derivatization of three of its four cysteine residues. These results indicate that rabeprazole is a promising candidate against American trypanosomiasis.

Efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for Helicobacter pylori initial treatment: A randomized controlled trial.

BACKGROUND: With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori. METHODS: This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed. RESULTS: A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05). CONCLUSIONS: The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.

The Efficacy of Morodan in Combination with Rabeprazole for the Treatment of Chronic Gastritis and its Impact on Gastric Mucosal Repair.

Objective: This study aimed to investigate the application and effectiveness of Morodan combined with rabeprazole in patients with chronic gastritis, focusing on its impact on gastric mucosa repair. Methods: A cohort of 109 patients diagnosed with chronic gastritis, who received treatment at our hospital between January 2020 and January 2021, were included in this study. Among them, 56 patients were assigned to the control group and received treatment with rabeprazole alone, while 53 were assigned to the research group and received a combination therapy of Morodan and rabeprazole. A comparative analysis was conducted between the two groups, assessing clinical efficacy, gastric mucosa repair effects, serum-related factors, and the incidence of adverse reactions. Results: The research group exhibited a higher total effective rate of treatment (94.64%) compared to the control group (79.25%) (P < .05). Following treatment, the research group showed lower levels of pepsinogen II, serum transforming growth factor α, serum epidermal growth factor, tumor necrosis factor-α, interleukin 6, and C-reactive protein compared to the control group (P < .05). Additionally, the research group displayed higher levels of pepsinogen I compared to the control group (P < .05). There was no significant difference in the incidence of adverse reactions between the research group and the control group (P > .05). Conclusions: The combination therapy of Morodan and rabeprazole demonstrates efficacy in the treatment of chronic gastritis. It promotes gastric mucosa repair, reduces inflammatory damage, and exhibits a higher safety profile with no significant increase in adverse reactions. This treatment approach holds a higher clinical application value.

Dyspepsia - The Indian perspective: A cross sectional study on demographics and treatment patterns of Dyspepsia from across India (Power 1.0 study).

BACKGROUND: Dyspepsia includes a spectrum of symptoms ranging from epigastric pain and early satiety to postprandial fullness. The worldwide prevalence of dyspepsia is 20-30%. It is slightly higher in the Western population and occurs more frequently among women. While the precise prevalence of dyspepsia in India is not available, different studies estimate that it affects 7.6-49% of the Indian population. Through our current study, we wanted to understand the demographics, clinical profile, patient presentation, and management in India. We also wanted to document the pattern of use of proton pump inhibitors (PPI) and patient satisfaction with PPIs in Indian patients with dyspepsia. MATERIALS AND METHODS: This pan-India, multi-centric, cross-sectional, questionnaire-based, noninterventional, observational study was conducted between February and October 2021 in patients >18 years of age with a clinical diagnosis of any form of dyspepsia. Descriptive statistics were used for categorical variables, and between-group comparisons were made using Fischer's exact test, with p < 0.05 denoting statistical significance. RESULTS: A total of 3,739 patients from across 29 states of India participated in the study. Most of the patients were male (70.8%) and were from urban areas (56.8%). The highest percentage of patients were aged 31-40 (33.8%), and most patients (60.2%) had dyspepsia for a duration of 6-12 months. Patients with functional dyspepsia (FD) (78.5%) were significantly higher compared to organic dyspepsia (OD) (21.5%) (p < 0.001). The most frequent presenting symptoms were epigastric pain, nausea, vomiting, and heartburn. A quarter (25.6%) of the dyspepsia patients were associated with various comorbid conditions, of which diabetes mellitus, hypertension, and irritable bowel syndrome are the most common ones. A total of 619 patients in the study were on concomitant medications, of which the most common were antidiabetic drugs (271/619, 43.8%). Rabeprazole was the most frequently used PPI (2467/3739, 66.0%) among the study participants. The patient satisfaction analysis showed that, overall, patients were satisfied with PPIs, as most patients (~80%) agreed to almost all questions. The analysis for individual PPIs showed the highest "agree" responses in the rabeprazole group for almost all questions (12 of 13). Around 86.4% of patients on rabeprazole agreed with "immediate relief from acidity," 84.9% for "gives me complete relief," and 85.9% for "relief from nighttime acidity symptoms." CONCLUSION: Our study involving over 3,700 Indian patients with Dyspepsia adds to the growing knowledge of dyspepsia in India. Dyspepsia is more prevalent in males and in the 31-50 age group. FD is the most common form. Overall, patients were satisfied with PPIs in dyspepsia management in India. Patients on rabeprazole showed higher levels of medication adherence, satisfaction with symptom relief, convenience of therapy, and safety compared to patients on other PPIs. Against the backdrop of a paucity of reliable data about dyspepsia in India, our study results provide valuable insights into Dyspepsia and its management in an Indian setting.

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.

Rabeprazole Coadministration Controls Ulcer Recurrence in Patients on Low-dose Aspirin Therapy: A Multicenter Prospective Study.

Objective To evaluate the efficacy and safety of rabeprazole coadministration with low-dose aspirin (LDA). Methods From 2015 to 2018, we conducted a large-scale, multicenter, prospective observational study to assess the safety and efficacy of treatment with rabeprazole (5 or 10 mg/day) in combination with LDA. Results The incidence of adverse reactions was 0.73% (11/1,513 patients), with no serious adverse reactions. We found no trend toward increases in the incidence of adverse reactions with increases in treatment duration. The cumulative recurrence rate of ulcers by Week 52 (Kaplan-Meier estimates) was 3.50% (range, 1.56-7.75%). No gastrointestinal bleeding was reported. Conclusion Rabeprazole in combination with LDA appears as safe and effective in real-world situations as in clinical trials.

Efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for Helicobacter pylori initial treatment: A randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori.@*METHODS@#This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed.@*RESULTS@#A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05).@*CONCLUSIONS@#The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.

Effectiveness of Rabeprazole and Other Proton Pump Inhibitors in Managing GERD with Varying Severity: A Retrospective, Real-world EMR-based Study (POWER GERD Study).

Purpose: To evaluate the effectiveness of rabeprazole and other proton pump inhibitors (PPIs) in providing symptomatic relief in patients with varying severity of gastroesophageal reflux disease (GERD). Methods: In this multicenter retrospective study, electronic medical records (EMRs) of GERD patients prescribed with PPIs at two Indian clinics/hospitals were reviewed (2016-2020). Rabeprazole's effectiveness was assessed at different follow-up visits and compared with other PPIs. Results: Overall, 269 patients (moderate and severe GERD: 84.39%) were included in three groups, viz rabeprazole, pantoprazole, and esomeprazole groups. A significant proportion of patients experienced quick and complete symptomatic relief at visit 1 with rabeprazole compared to the baseline visit, which gradually increased till visit 4 for both daytime [viz heartburn (38.78-93.88%; p < 0.001)] and nocturnal symptoms [viz sleep disturbances (62.92-97.75%; p < 0.001)]. Rabeprazole provided quick relief at visit 1 when compared with pantoprazole for daytime heartburn (38.78 vs 5.56%; p = 0.01), daytime epigastric pain (66.04 vs 12.12%; p = 0.049), and nocturnal water brash (60.71 vs 16.13%; p = 0.015), and when compared with esomeprazole for nocturnal nausea (82.61 vs 20.00%; p = 0.013). Further, the proportion of patients exhibiting complete treatment response was relatively higher in the rabeprazole group (83.33%) than in the pantoprazole (62.07%) and esomeprazole (65.67%) groups at visit 4. Conclusion: Rabeprazole was effective in providing quick and sustained relief for both daytime and nocturnal GERD symptoms in patients with moderate and severe GERD. Rabeprazole also demonstrated greater effectiveness when compared with pantoprazole and esomeprazole in reducing the severity of multiple GERD symptoms. How to cite this article: Lawate P, Jilawar N, Vyas K, et al. Effectiveness of Rabeprazole and Other Proton Pump Inhibitors in Managing GERD with Varying Severity: A Retrospective, Real-world EMR-based Study (POWER GERD Study). J Assoc Physicians India 2023;71(10):37-44.

Effect and safety of anaprazole in the treatment of duodenal ulcers: a randomized, rabeprazole-controlled, phase III non-inferiority study.

BACKGROUND: The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori ) infection status and CYP2C19 polymorphism on anaprazole. METHODS: In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. RESULTS: The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). CONCLUSIONS: The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers. REGISTRATION: ClinicalTrials.gov, NCT04215653.

A randomized controlled trial to compare Helicobacter pylori eradication rates between the empirical concomitant therapy and tailored therapy based on 23S rRNA point mutations.

BACKGROUND: Increasing clarithromycin resistance has led to changes in several guidelines for treatment of Helicobacter pylori infections. We compared the H. pylori eradication rates of the empirical concomitant therapy (CoT) and a tailored therapy (TaT) using dual-priming oligonucleotide-based polymerase chain reaction to detect mutations in the 23S rRNA gene that are related to clarithromycin resistance. METHODS: Between June 2020 and May 2021, 290 patients were enrolled and randomly assigned to 2 groups. In the CoT group, the patients received rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 14 days. In the TaT group, point mutation-negative patients received rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 14 days and point mutation-positive patients received rabeprazole 20 mg twice daily, metronidazole 500 mg thrice daily, and bismuth 120 mg and tetracycline 500 mg 4 times daily for 14 days. RESULTS: A total of 290 and 261 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. A2142G and/or A2143G point mutations were identified in 28.6% of the patients. No significant difference in eradication rates were observed between the 2 groups as per ITT (CoT, 82.8% and TaT, 85.5%, P = .520) and PP (CoT, 88.6% and TaT, 94.6%, P = .084) analyses. In point mutation-positive patients, the eradication rates in the CoT group were lower than those in the TaT group as per ITT (69.8% and 87.5%, respectively, P = .050) and PP (76.9% and 97.1%, respectively, P = .011) analyses. CONCLUSION: CoT and TaT showed similar overall eradication rates for H. pylori. However, CoT eradication rate was suboptimal, especially in point mutation-positive patients.

Metagenomic Changes of Gut Microbiota following Treatment of Helicobacter pylori Infection with a Simplified Low-Dose Quadruple Therapy with Bismuth or Lactobacillus reuteri.

BACKGROUND: Probiotic supplementation to antibiotic regimens against Helicobacter pylori infection has been proposed to improve eradication rate and to decrease detrimental effects on gut microbiota. AIMS: To evaluate microbiota modifications due to a low-dose quadruple therapy with bismuth or Lactobacillus reuteri. METHODS: Forty-six patients infected with H. pylori were prospectively enrolled in a single-centre, randomized controlled trial to receive b.i.d. with meals for 10 days low-dose quadruple therapy consisting of rabeprazole 20 mg and bismuth (two capsules of Pylera® plus 250 mg each of tetracycline and metronidazole), or the same dose of rabeprazole and antibiotics plus Gastrus® (L. reuteri), one tablet twice-a-day for 27 days. Stool samples were collected at the enrolment, at the end and 30-40 days after the treatment. Gut microbiota composition was investigated with 16S rRNA gene sequencing. RESULTS: Eradication rate was by ITT 78% in both groups, and by PP analysis 85.7% and 95.5% for Gastrus® and bismuth group, respectively. Alpha and beta diversity decreased at the end of treatment and was associated with a reduction of bacterial genera beneficial for gut homeostasis, which was rescued 30-40 days later in both groups, suggesting a similar impact of the two regimens in challenging bacterial community complexity. CONCLUSIONS: Low-dose bismuth quadruple therapy proved to be effective with lower costs and amount of antibiotics and bismuth. Gastrus® might be an option for patients with contraindications to bismuth. L. reuteri was unable to significantly counteract dysbiosis induced by antibiotics. How to administer probiotics to prevent gut microbiota alterations remains an open question.

The efficacy of culture-guided versus empirical therapy with high-dose proton pump inhibitor as third-line treatment of Helicobacter pylori infection: A real-world clinical experience.

BACKGROUND AND AIM: Most consensuses recommend culture-guided therapy as third-line Helicobacter pylori treatment. This study aimed to investigate the efficacies of culture-guided therapy and empirical therapy with high-dose proton pump inhibitor (PPI) in the H. pylori third-line treatment. METHODS: Between August 2012 and October 2021, H. pylori-infected patients with at least two failed eradication attempts received anti-H. pylori therapy according to the results of antimicrobial sensitivity tests plus high-dose rabeprazole and/or bismuth. They were categorized into three groups: patients who had positive results of culture with equal to or more than three susceptible antibiotics were treated by culture-guided non-bismuth quadruple therapy, patients who had positive results of culture with one or two susceptible antibiotics were treated by culture-guided bismuth-containing therapy, and patients who had a negative result of culture were treated by an empirical therapy with high-dose rabeprazole plus amoxicillin, tetracycline and levofloxacin. A post-treatment assessment was conducted at week 8. RESULTS: We recruited 126 patients. The eradication rates of culture-guided non-bismuth quadruple therapy (n = 50), culture-guided bismuth-containing therapy (n = 46) and empirical therapy (n = 30) were 84.0%, 87.0%, and 66.7% (95% confidence interval: 73.8-94.2%, 77.3-96.7%, and 49.8-83.6%), respectively. Overall, culture-guided therapy achieved a higher eradication rate than empirical therapy (85.4% vs 66.7%; 95% confidence interval, 0.4% to 37.0%, P = 0.022). CONCLUSIONS: Culture-guided therapy with high-dose PPI achieves a higher eradication rate than empirical therapy with high-dose PPI in the third-line treatment of H. pylori infection. The eradication rate of rescue therapy with bismuth plus two susceptible antibiotics is not inferior to that with three susceptible antibiotics.

Rabeprazole Promotes Vascular Repair and Resolution of Sepsis-Induced Inflammatory Lung Injury through HIF-1α.

There are currently no effective treatments for sepsis and acute respiratory distress syndrome (ARDS). The repositioning of existing drugs is one possible effective strategy for the treatment of sepsis and ARDS. We previously showed that vascular repair and the resolution of sepsis-induced inflammatory lung injury is dependent upon endothelial HIF-1α/FoxM1 signaling. The aim of this study was to identify a candidate inducer of HIF-1α/FoxM1 signaling for the treatment of sepsis and ARDS. Employing high throughput screening of a library of 1200 FDA-approved drugs by using hypoxia response element (HRE)-driven luciferase reporter assays, we identified Rabeprazole (also known as Aciphex) as a top HIF-α activator. In cultured human lung microvascular endothelial cells, Rabeprazole induced HIF1A mRNA expression in a dose-dependent manner. A dose-response study of Rabeprazole in a mouse model of endotoxemia-induced inflammatory lung injury identified a dose that was well tolerated and enhanced vascular repair and the resolution of inflammatory lung injury. Rabeprazole treatment resulted in reductions in lung vascular leakage, edema, and neutrophil sequestration and proinflammatory cytokine expression during the repair phrase. We next used Hif1a/Tie2Cre knockout mice and Foxm1/Tie2Cre knockout mice to show that Rabeprazole promoted vascular repair through HIF-1α/FoxM1 signaling. In conclusion, Rabeprazole is a potent inducer of HIF-1α that promotes vascular repair and the resolution of sepsis-induced inflammatory lung injury via endothelial HIF-1α/FoxM1 signaling. This drug therefore represents a promising candidate for repurposing to effectively treat severe sepsis and ARDS.

Identification of novel and potential PPARγ stimulators as repurposed drugs for MCAO associated brain degeneration.

Peroxisome proliferator-activated receptor-gamma (PPARγ) has been shown to have therapeutic promise in the treatment of ischemic stroke and is supported by several studies. To identify possible PPARγ activators, the current study used an in silico technique in conjunction with molecular simulations and in vivo validation. FDA-approved drugs were evaluated using molecular docking to determine their affinity for PPARγ. The findings of molecular simulations support the repurposing of rabeprazole and ethambutol for the treatment of ischemic stroke. Adult Sprague Dawley rats were subjected to transient middle cerebral artery occlusion (t-MCAO). Five groups were made as a sham-operated, t-MCAO group, rabeprazole +t-MCAO, ethambutol +t-MCAO, and pioglitazone +t-MCAO. The neuroprotective effects of these drugs were evaluated using the neurological deficit score and the infarct area. The inflammatory mediators and signaling transduction proteins were quantified using Western blotting, ELISA, and immunohistochemistry. The repurposed drugs mitigated cerebral ischemic injury by PPARγ mediated downregulation of nods like receptor protein 3 inflammasomes (NLRP3), tumor necrosis factor-alpha (TNF-α), cyclooxygenase 2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-kB), and c-Jun N-terminal kinase (p-JNK). Our data demonstrated that rabeprazole and ethambutol have neuroprotective potential via modulating the cytoprotective stress response, increasing cellular survival, and balancing homeostatic processes, and so may be suitable for future research in stroke therapy.

Protocol of a randomized, double-blind, placebo-controlled study of the effect of probiotics on the gut microbiome of patients with gastro-oesophageal reflux disease treated with rabeprazole.

BACKGROUND: For patients with gastro-oesophageal reflux symptoms, the preferred treatment is proton pump inhibitor (PPI) administration for approximately 8 weeks. However, long-term use of PPIs can cause gut microbiome (GM) disturbances. This study is designed to evaluate the effect of probiotics combined with a PPI on the GM and gastrointestinal symptoms of patients with gastro-oesophageal reflux disease (GERD). METHOD: This is a randomized, double-blind, placebo-controlled trial. A total of 120 eligible patients with GERD will be randomized into the experimental group or the control group. The treatment includes two phases: the initial treatment period lasts 8 weeks (weeks 1-8), and the maintenance treatment period lasts 4 weeks (weeks 9-12). During the initial treatment period, the experimental group will take rabeprazole and LiHuo probiotics, and the control group will take rabeprazole and a probiotic placebo; during the maintenance treatment period, the experimental group will take LiHuo probiotics, and the control group will take a probiotic placebo. The primary measure is the change in the GM. The secondary measures are the Reflux Disease Questionnaire (RDQ) score, Gastrointestinal Symptom Rating Scale (GSRS) score, faecal metabolome (FM), body mass index, Los Angeles grade of oesophagitis, adverse event (AE) rate and treatment compliance. Each outcome indicator will be assessed at day 0 (before administration), day 28 and/or 56 (during administration), and day 84 (end of administration) to reveal intragroup differences. AEs will be monitored to assess the safety of LiHuo probiotics. DISCUSSION: This will be the first trial to use the intestinal flora metagene method to analyse the effects of probiotics on patients with GERD receiving long-term PPI treatment. The goal is to provide evidence for the use of probiotics to reduce intestinal flora disorders and other symptoms of gastrointestinal discomfort in patients with GERD who have used PPIs for a long period. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) (NO. ChiCTR2000038409). Registered on November 22, 2020, http://www.chictr.org.cn/showproj.aspx?proj=56358 .