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 ).

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.

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.

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 plus amoxicillin dual therapy is equally effective to bismuth-containing quadruple therapy for Helicobacter pylori eradication in central China: A single-center, prospective, open-label, randomized-controlled trial.

BACKGROUND: Antibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High-dose dual therapy has recently shown encouraging results in H. pylori eradication, but it has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first-line therapy for H. pylori eradication, and factors that affect the curing rate. METHODS: This is a single-center, prospective, open-label, randomized-controlled trial. Naive patients (n=292) were randomly treated with bismuth-containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by 13 C-urea breath test. RESULTS: In per-protocol (PP) analysis, H. pylori eradication rate was 91.2% in BQT group, 89.6% in RADT, and 51.0% in RFDT group. In intention-to-treat (ITT) analysis, infection was eradicated in 86.7% of patients in BQT group, 85.8% in RADT, and 48.1% in RFDT groups, respectively. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group. CONCLUSIONS: Rabeprazole-amoxicillin dual therapy is equally effective to the bismuth-containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non-smoking condition, which deserves future stratified analysis for refinement and optimization.

Different dose of new generation proton pump inhibitors for the treatment of Helicobacter pylori infection: A meta-analysis.

The evidence on whether high-dose new generation proton pump inhibitors (PPIs) including rabeprazole and esomeprazole achieve a higher eradication rate of Helicobacter pylori has not been assessed. The primary comparison was eradication and adverse events (AEs) rate of standard (esomeprazole 20 mg bid, rabeprazole 10 mg bid) versus high-dose (esomeprazole 40 mg bid, rabeprazole 20 mg bid) PPIs. Sub-analyses were performed to evaluate the eradication rate between Asians and Caucasians, clarithromycin-resistance (CAM-R) strains, and clarithromycin-sensitivity (CAM-S) strains of different dose PPIs. We conducted a literature search for randomized controlled trials comparing high-with standard-dose esomeprazole and rabeprazole for H. pylori eradication and AEs. A total of 12 trials with 2237 patients were included. The eradication rate of high-dose PPIs was not significantly superior to standard-dose PPIs regimens: 85.3% versus 84.2%, OR 1.09 (0.86-1.37), P = 0.47. The high dose induced more AEs than those of the standard dose, but didn't reach statistical significance (OR 1.25, 95% CI: 0.99-1.56, P = 0.06). Subgroup analysis showed that the difference in eradication rate of PPIs between high- and standard-dose groups were not statistically significant both in Asians (OR 0.99, 95% CI 0.75-1.32, P = 0.97) and Caucasians (OR 1.27, 95% CI 0.84-1.92, P = 0.26). Furthermore, there were similar eradication rates in CAM-S (OR 1.2; 95% CI 0.58-2.5; P = 0.63) and CAM-R strains (OR 1.08; 95% CI 0.45-2.56; P = 0.87) between the standard-and high-dose groups. High and standard dosages of new generation of the PPIs showed similar H. pylori eradication rates and AEs as well as between Asian versus Caucasian populations, with or without clarithromycin-resistance. However, further studies are needed to confirm.

Therapeutic efficacy and safety of Kangfuxin in combination with rabeprazole in the treatment of peptic ulcer: A systematic review and meta-analysis.

BACKGROUND: Kangfuxin (KFX), a well-known Chinese patent medicine which extracted from Periplaneta americana, is widely used as an adjuvant in the treatment of peptic ulcers (PUs) with proton pump inhibitors (PPIs) such as rabeprazole, in China. However, no clear consensus has been reached on the efficacy for PU treatment. METHODS: We searched in 7 electronic databases to find randomized controlled trials (RCTs) completed before May 31, 2020 to explore the clinical efficiency of KFX plus rabeprazole in the treatment of PU. Risk ratio (RR) corresponding to 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by both Egger's and Begg's tests. Statistical analyses were performed using RevMan 5.4 and Stata version 10.0. RESULTS: Twenty-five RCTs, comprising 2555 PU patients, were included in this study. Meta-analysis showed that, when compared with rabeprazole-based treatment alone, KFX plus rabeprazole significantly improved the healing rate (RR = 1.34, 95% CI 1.25-1.44) and overall response rate of ulcers (RR = 1.16, 95% CI 1.13-1.20), alleviated the clinical symptoms of PU (RR = 1.14, 95% CI 1.08-1.21), and reduced the recurrence of PU (RR = 0.38, 95% CI 0.24-0.61) without an increase in the occurrence of adverse events (RR = 0.92, 95% CI 0.66-1.28). CONCLUSION: Our study suggests that KFX combined with rabeprazole showed positive therapeutic effects and is safe for treating PU, which may provide more reliable evidence for the clinical use of KFX in the treatment of PU.

Amoxicillin or tetracycline in bismuth-containing quadruple therapy as first-line treatment for Helicobacter pylori infection.

AIM: To compare the efficacy and safety between modified quadruple- and bismuth-containing quadruple therapy as first-line eradication regimen for Helicobacter pylori infection. METHODS: This study was a multicenter, randomized-controlled, non-inferiority trial. Subjects endoscopically diagnosed with H. pylori infection were randomly allocated to receive modified quadruple- (rabeprazole 20 mg bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid [elemental bismuth 480 mg]; PAMB) or bismuth-containing quadruple therapy (rabeprazole 20 mg bid, bismuth subcitrate 300 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid; PBMT) for 14 days. Rates of eradication success and adverse events were investigated. Antibiotic resistance was determined using the agar dilution and DNA sequencing of the clarithromycin resistance point mutations in the 23 S rRNA gene of H. pylori. RESULTS: In total, 233 participants were randomized, 27 were lost to follow-up, and four violated the protocol. Both regimens showed an acceptable eradication rate in the intention-to-treat (PAMB: 87.2% vs. PBMT: 82.8%, P = .37), modified intention-to-treat (96.2% vs. 96%, P > .99), and per-protocol (96.2% vs. 96.9%, P > .99) analyses. Non-inferiority in the eradication success between PAMB and PBMT was confirmed. The amoxicillin-, metronidazole-, tetracycline-, clarithromycin-, and levofloxacin-resistance rates were 8.3, 40, 9.4, 23.5, and 42.2%, respectively. Antimicrobial resistance did not significantly affect the efficacy of either therapy. Overall compliance was 98.1%. Adverse events were not significantly different between the two therapies. CONCLUSION: Modified quadruple therapy comprising rabeprazole, amoxicillin, metronidazole, and bismuth is an effective first-line treatment for the H. pylori infection in regions with high clarithromycin and metronidazole resistance.

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.

First characterization of a microsporidial triosephosphate isomerase and the biochemical mechanisms of its inactivation to propose a new druggable target.

The microsporidia are a large group of intracellular parasites with a broad range of hosts, including humans. Encephalitozoon intestinalis is the second microsporidia species most frequently associated with gastrointestinal disease in humans, especially immunocompromised or immunosuppressed individuals, including children and the elderly. The prevalence reported worldwide in these groups ranges from 0 to 60%. Currently, albendazole is most commonly used to treat microsporidiosis caused by Encephalitozoon species. However, the results of treatment are variable, and relapse can occur. Consequently, efforts are being directed toward identifying more effective drugs for treating microsporidiosis, and the study of new molecular targets appears promising. These parasites lack mitochondria, and oxidative phosphorylation therefore does not occur, which suggests the enzymes involved in glycolysis as potential drug targets. Here, we have for the first time characterized the glycolytic enzyme triosephosphate isomerase of E. intestinalis at the functional and structural levels. Our results demonstrate the mechanisms of inactivation of this enzyme by thiol-reactive compounds. The most striking result of this study is the demonstration that established safe drugs such as omeprazole, rabeprazole and sulbutiamine can effectively inactivate this microsporidial enzyme and might be considered as potential drugs for treating this important disease.

Ten-Day Quadruple Therapy Comprising Low-Dose Rabeprazole, Bismuth, Amoxicillin, and Tetracycline Is an Effective and Safe First-Line Treatment for Helicobacter pylori Infection in a Population with High Antibiotic Resistance: a Prospective, Multicenter, Randomized, Parallel-Controlled Clinical Trial in China.

The objective of this study was to investigate the efficacy and safety of 10-day bismuth quadruple therapy with amoxicillin, tetracycline, or clarithromycin and different doses of rabeprazole for first-line treatment of Helicobacter pylori infection. This multicenter, randomized, parallel-controlled clinical trial was conducted between March 2013 and August 2014. A total of 431 H. pylori-infected patients with duodenal ulcers were enrolled and randomized into four treatment groups (1:1:1:1) for 10 days, as follows: (i) a group receiving a low dose of rabeprazole of 10 mg twice a day (b.i.d.) (LR dose) plus bismuth, amoxicillin, and clarithromycin (LR-BAC); (ii) a group receiving LR plus bismuth, amoxicillin, and tetracycline (LR-BAT); (iii) a group receiving a high dose of rabeprazole of 20 mg b.i.d. (HR dose) plus bismuth, amoxicillin, and clarithromycin (HR-BAC); and (iv) a group receiving HR-BAT. Antimicrobial susceptibility was assessed by the Etest method. The primary outcome was H. pylori eradication at 4 weeks after the treatment. The per-protocol (PP) eradication rates in the LR-BAC, LR-BAT, HR-BAC, and HR-BAT groups were 94.1%, 91.9%, 94.8%, and 91.9%, respectively, while the intention-to-treat (ITT) eradication rates in those groups were 87.2%, 87.2%, 87.7%, and 86%, respectively. There was no significant difference between the four groups in PP analysis (P = 0.799) and ITT analysis (P = 0.985). The efficacies of four-treatment therapy were not affected by antibiotic resistance. The adverse events in the four treatment groups were similar; central nervous system (CNS) and gastrointestinal symptoms were the most common reported. Bismuth-containing quadruple therapy with low-dose rabeprazole, amoxicillin, and tetracycline is a good option for first-line treatment of H. pylori infection in a population with high antibiotic resistance. (This study is registered at Chinese Clinical Trials Registry [www.chictr.org.cn] under number ChiCTR1800014832.).

[The Efficacy of Moxifloxacin-containing Triple Therapy after Hybrid Therapy Failure in Helicobacter pylori Eradication].

BACKGROUND/AIMS: Hybrid therapy was successful in eradicating Helicobacter pylori (H. pylori) according to previous reports. However, to the best of our knowledge, there have only been a few studies evaluating the optimal choice after hybrid failure. Hence, we aimed to evaluate the efficacy of moxifloxacin-containing triple therapy after hybrid therapy failure in H. pylori eradication. METHODS: Between January 2013 and March 2016, we retrospectively reviewed patients who underwent failed hybrid therapy, as first line treatment, in eradicating H. pylori (rabeprazole and amoxicillin b.i.d for 14 days, in addition to clarithromycin and metronidazole b.i.d for final 7 days). Then, we investigated the eradication rates of moxifloxacin-containing triple therapy (rabeprazole, amoxicillin b.i.d and moxifloxacin qd) as the second line of treatment. Intention-to-treat (ITT) and per-protocol (PP) analyses were used to determine the eradication rate. We evaluated the status of H. pylori by using 13C-urea breath test 6 weeks after the final treatment. Moreover, compliance and adverse effects of each patient were analyzed. RESULTS: Among those who failed the initial hybrid therapy, 11 patients received moxifloxacin-containing triple therapy. The overall eradication rates, as determined by ITT and PP, were 72.7% (n=8/11) and 80% (n=8/10), respectively. The compliance rate was 100%, and there were no serious adverse effects. CONCLUSIONS: Moxifloxacin-containing triple therapy can be used as a second line therapy in case of hybrid therapy failure. A large scale study is necessary to confirm the findings of this study and establish clinical evidence.

A Non-Inferiority Study: Modified Dual Therapy Consisting Higher Doses of Rabeprazole Is as Successful as Standard Quadruple Therapy in Eradication of Helicobacter pylori.

The aim is to compare high-dose rabeprazole and amoxicillin containing modified dual therapy (MDT) with bismuth subcitrate containing standard quadruple therapy (SQT) as the first-line Helicobacter pylori eradication treatment in terms of efficacy, safety, and adherence to treatment. A total of 200 consecutive patients diagnosed endoscopically with nonulcer dyspepsia with H. pylori infection were randomly assigned into 2 groups, 1 treated with amoxicillin 750 mg thrice daily plus rabeprazole 20 mg thrice daily (MDT group) or rabeprazole 20 mg b.i.d., bismuth subcitrate 120 mg q.i.d., tetracycline 500 mg q.i.d., metronidazole 500 mg t.i.d. (SQT group). Overall, 196 patients (98 in the MDT group and 98 in the SQT group) completed the study. H. pylori eradication was achieved in 84.7% of patients in the MDT group by intention to treat analysis and 84.9% by per-protocol analysis, which were comparable with SQT group (87.8% and 88.8%, respectively). Adverse events including nausea (P = 0.03), dysgeusia (P < 0.001), diarrhea (P = 0.001), black colored stool (P < 0.001), headache (P = 0.01), and abdominal pain (P = 0.05) were significantly higher in SQT group. The MDT is an efficient and safe treatment choice that could be recommended in the first-line eradication treatment of H. pylori.

Analysis of the cost-effectiveness of using vonoprazan-amoxicillin-clarithromycin triple therapy for first-line Helicobacter pylori eradication.

BACKGROUND: Vonoprazan (VPZ)-based triple therapy has been reported to have greater efficacy than a proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) eradication. However, because VPZ is more expensive than PPIs such as rabeprazole (RPZ), economic evaluation is essential. METHODS: We performed a retrospective study on 209 patients who underwent first-line eradication of H. pylori infection in Fuyoukai Murakami Hospital from 1 March 2015 to 31 March 2016. Patients who received VPZ, amoxicillin (AMPC) and clarithromycin (CAM) were assigned to the VPZ/AC group (n = 111) and patients who received RPZ, AMPC and CAM to the RPZ/AC group (n = 98). We compared the patients' backgrounds, including age, gender, use of high-dose CAM, past history of peptic ulcer, smoking and drug-related adverse events between the two groups. We defined cost as direct medical costs per patient and effectiveness as the first-line eradication rate in the intention-to-treat (ITT) analysis and analyzed the cost-effectiveness using the cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER). RESULTS: There was no significant difference in the patients' backgrounds. The ITT analysis revealed an eradication rate of 94.6% for VPZ/AC and 86.7% for RPZ/AC. VPZ/AC cost 1155.4 Japanese yen (JPY) higher than RPZ/AC (34063.4 vs. 32908.0, JPY). CER of VPZ/AC was less than that of RPZ/AC (360.1 vs. 379.4, JPY per percent) and ICER of VPZ/AC was 147.0 JPY (1.28 Euro (EUR), 1 EUR =115 JPY) per percent. CONCLUSIONS: VPZ/AC was more cost-effective than RPZ/AC as first-line therapy for H. pylori eradication.

Short-term and long-term effect of diaphragm biofeedback training in gastroesophageal reflux disease: an open-label, pilot, randomized trial.

This study investigated the effectiveness of diaphragm biofeedback training (DBT) for patients with gastroesophageal reflux disease (GERD). A total of 40 patients with GERD treated at the Peking Union Medical College Hospital between September 2004 and July 2006 were randomized to receive DBT and rabeprazole proton pump inhibitor (PPI) or rabeprazole alone. The DBT + rabeprazole group received DBT during the 8-week initial treatment; the rabeprazole group did not. During the 6-month follow up, all patients took acid suppression according to their reflux symptoms, and the patients in the DBT + rabeprazole group were required to continue DBT. The primary outcome (used for power analysis) was the amount of acid suppression used at 6 months. Secondary outcomes were reflux symptoms, health-related quality of life (HRQL), and esophageal motility differences after the 8-week treatment compared with baseline. Acid suppression usage significantly decreased in the DBT + rabeprazole group compared with the rabeprazole group at 6 months (P < 0.05). At 8 weeks, reflux symptoms and GERD-HRQL were significantly improved in both groups (P < 0.05), without difference between them. Crural diaphragm tension (CDT) and gastroesophageal junction pressure (GEJP) significantly increased in the DBT + rabeprazole group (P < 0.05), but without change in lower esophageal sphincter (LES) pressure. There was no significant change in CDT, GEJP, and LES pressure compared with baseline in the rabeprazole group. In conclusion, long-term DBT could reduce acid suppression usage by enhancing the anti-reflux barrier, providing a non-pharmacological maintenance therapy and reducing medical costs for patients with GERD.

High Helicobacter pylori cure rate with sitafloxacin-based triple therapy.

BACKGROUND: Bacterial resistance of Helicobacter pylori to antibiotics is increasing and it often leads to failure of antibiotic treatment. A new sitafloxacin-based triple therapy was developed to counter this situation; the fluoroquinolone sitafloxacin has a low minimum inhibitory concentration for H. pylori. AIM: To investigate the efficacy in Japanese patients of sitafloxacin-based triple therapy and document its efficacy in relation to anti-microbial susceptibility. METHODS: We investigated the efficacy of a 1-week sitafloxicin-based regimen of rabeprazole 10 mg four times daily (q.d.s.), metronidazole 250 mg twice daily (b.d.) and sitafloxacin 100 mg b.d. in 180 H. pylori-positive Japanese patients (first-line treatment: n = 45, second-line; n = 41, third-line: n = 94). At 8 weeks, patients were given the (13) C-urea breath test to assess eradication status. RESULTS: Eradication rate was 92.2% [95% confidence interval (CI): 87.3-95.7%, 166/180] in intention-to-treat analysis. Although the eradication rate was higher in patients treated with first-line therapy [45/45 (100%, 95% CI: 83.4-100%)] than in those with second- [38/41 (92.7%, 80.1-98.5%)] or third-line therapy [83/94 (88.3%, 80.0-94.0%)], no significant differences were noted with respect to the number of previous therapy attempts (P = 0.054). Eradication rates in patients infected with sensitive- and resistant strains to metronidazole were 96.6% (28/29) and 96.3% (77/80) (P = 0.941), respectively, while rates were 98.4% (60/61) in sitafloxacin-sensitive and 50.0% (1/2) in sitafloxacin resistant strains (P < 0.001). CONCLUSION: Sitofloxacin-based triple therapy with metronidazole b.d. and rabeprazole q.d.s. achieved an eradication rate exceeding 88%, irrespective of eradication history, CYP2C19 genotype, or metronidazole resistance status.

The efficacy of moxifloxacin-containing triple therapy after standard triple, sequential, or concomitant therapy failure for Helicobacter pylori eradication in Korea.

BACKGROUND/AIMS: Retreatment after initial treatment failure for Helicobacter pylori is very challenging. The purpose of this study was to evaluate the efficacies of moxifloxacin-containing triple and bismuth-containing quadruple therapy. METHODS: A total of 151 patients, who failed initial H. pylori treatment, were included in this retrospective cohort study. The initial regimens were standard triple, sequential, or concomitant therapy, and the efficacies of the two following second-line treatments were evaluated: 7-day moxifloxacin-containing triple therapy (rabeprazole 20 mg twice a day, amoxicillin 1,000 mg twice a day, and moxifloxacin 400 mg once daily) and 7-day bismuth-containing quadruple therapy (rabeprazole 20 mg twice a day, tetracycline 500 mg 4 times a day, metronidazole 500 mg 3 times a day, and tripotassium dicitrate bismuthate 300 mg 4 times a day). RESULTS: The overall eradication rates after moxifloxacin-containing triple therapy and bismuth-containing quadruple therapy were 69/110 (62.7%) and 32/41 (78%), respectively. Comparison of the two regimens was performed in the patients who failed standard triple therapy, and the results revealed eradication rates of 14/28 (50%) and 32/41 (78%), respectively (p=0.015). The frequency of noncompliance was not different between the two groups, and there were fewer adverse effects in the moxifloxacin-containing triple therapy group (2.8% vs 7.3%, p=0.204 and 25.7% vs 43.9%, p=0.031, respectively). CONCLUSIONS: Moxifloxacin-containing triple therapy, a recommended second-line treatment for initial concomitant or sequential therapy failure, had insufficient efficacy.

Clinical characteristics of elderly patients with proton pump inhibitor-refractory non-erosive reflux disease from the G-PRIDE study who responded to rikkunshito.

BACKGROUND: The incidence and severity of gastroesophageal reflux disease (GERD) in Japan tends to increase in elderly women. Rikkunshito (RKT), a traditional Japanese medicine, acts as a prokinetic agent and improves gastric emptying and gastric accommodation. Our previous prospective randomized placebo-controlled study showed that RKT combined with a standard-dose of rabeprazole (RPZ) significantly improved the acid-related dysmotility symptoms (ARD) in elderly patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study aimed to evaluate clinical characteristics of elderly PPI-refractory NERD patients with ARD symptoms who responded to RKT. METHODS: Two hundred forty-two patients with PPI-refractory NERD were randomly assigned to 8 weeks of either RPZ (10 mg/q.d.) + RKT (7.5 g/t.i.d.) (RKT group) or RPZ + placebo (PL group). Among them, 95 were elderly (≥65 years) with ARD (RKT group: n = 52; PL group: n = 43). We analyzed the changes using the 12 subscale score of frequency scale for the symptoms of GERD (FSSG) and 15 items of the Gastrointestinal Symptom Rating Scale at 4 and 8 weeks and compared the therapeutic efficacy between the 2 groups. RESULTS: There were no marked differences in baseline demographic or clinical characteristics in the 2 groups except for rate of current smoking. The FSSG score (mean ± SD at 0, 4, and 8 weeks) in both the RKT (16.0 ± 7.0; 9.9 ± 8.4; 7.0 ± 6.4) and PL (15.1 ± 6.4; 10.9 ± 6.7, 11.1 ± 8.5) groups significantly decreased after treatment. However, the degree of improvement of total and ARD scores of FSSG after the 8-week treatment was significantly greater in the RKT group than in the PL group. Combination therapy with RKT for 8 weeks showed significant improvement in 3 subscale scores (abdominal bloating, heavy feeling in stomach and sick feeling after meals) of the ARD domain and 1 subscale score (heartburn after meals) of the reflux symptom domain. CONCLUSIONS: RKT may be useful for improving GERD symptoms in elderly PPI-refractory NERD patients with ARD. Thus, RKT was particularly effective for resolving postprandial GERD symptoms (heavy feeling in stomach, sick feeling, and heartburn after meals). TRIAL REGISTRATION: (UMIN000005880).