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Background Approximately 30% of patients who are treated with proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD) experience persistent symptoms. No prokinetic agent regiments are useful for symptom relief. Aims This study was conducted to examine the effect of adding acotiamide to PPI or vonoprazan refractory GERD. Methods This was a randomized, prospective, double-blind, placebo-controlled trial. Seventy-one patients were enrolled. Patients underwent upper endoscopy before initial therapy [15 reflux esophagitis and 55 non-erosive reflux disease (NERD)]. Patients with persistent reflux symptoms were administered 300 mg/day acotiamide or placebo for 2 weeks. The primary endpoint was overall treatment effect (OTE), and gastrointestinal symptoms were evaluated. High-resolution manometry (HRM) and 24-h multiple intraluminal impedance-pH (MII-pH) monitoring were conducted before and after treatment when possible. Results Seventy patients were randomized (35 acotiamide and 35 placebo). Sixteen and 10 patients in the acotiamide and placebo groups, respectively, completed MII-pH and HRM. The OTE improvement rates were 28.6% and 14.3% in patients administered acotiamide and placebo, respectively (p = 0.145). In patients with NERD, however, the OTE improvement rate and responder rate for regurgitation in the acotiamide group was significantly higher than those in the placebo group (29.6 vs. 7.1%; p = 0.030, 37.0 vs. 10.7%; p = 0.021, respectively). Acotiamide significantly reduced the total reflux episodes (p = 0.001), acid (p = 0.020), proximal reflux (p = 0.007), and liquid reflux (p = 0.013) episodes. Conclusion Adding acotiamide to gastric acid inhibitors can improve symptoms in patients with refractory NERD.

Gastroesophageal reflux disease (GERD) is a common disorder, and is typically treated with proton-pump inhibitors (PPIs) as the recommended first-line therapy. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. It is uncertain whether the standard dose of vonoprazan 20 mg is superior to that of PPIs for GERD, so a direct comparison of the therapeutic effects and adverse events between vonoprazan 20 mg and PPIs is needed. MEDLINE, the Cochrane Central Register of Controlled Trials, and Embase were chosen as the literature sources. Randomized controlled trials for vonoprazan 20 mg and PPIs published in English were searched. Data from studies meeting the eligibility criteria were extracted individually by two researchers and compared to maintain consistency. Fifty-six articles were identified in the databases, and one study was manually searched and added to the analysis, ultimately yielding six eligible studies. For the main analysis, the risk ratios (RR) of efficacy and adverse events between vonoprazan and PPIs were 1.06 (0.99–1.13) and 1.08 (0.96–1.22), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher results for vonoprazan than lansoprazole, with an RR of 1.14 (1.06–1.22). Our findings suggest that vonoprazan is non-inferior to PPIs as therapy for patients with GERD. Subgroup analysis indicates that vonoprazan is more effective than PPIs for patients with severe erosive esophagitis. The safety outcomes for vonoprazan are similar to those for PPIs.

Vonoprazan fumarate (TAK-438) is a novel potassium-competitive acid blocker that appears to exert a longer/more potent antisecretory effect than lansoprazole due to high accumulation/slow clearance from the gastric glands. However, there is no direct evidence that vonoprazan selectively accumulates in gastric parietal cells of gastric glands.To investigate the distribution of radioactivity in the rat stomach after single intravenous administration of [(3)H]-labeled vonoprazan.Autoradioluminography of the stomach revealed that at 5 h after administration, radioactivity levels in the corpus mucosal layer was higher than radioactivity levels in the muscular layer, pylorus, and forestomach. At 24 h, although overall radioactivity was significantly decreased, the highest radioactivity was still observed in the mucosal layer. Accumulation of radioactivity in gastric parietal cells was quantitatively analyzed using microautoradiography. The number of silver granules in parietal cells from vonoprazan-injected rats was higher than in cells from a saline-injected rat. At 24 h, the number of granules was approximately at 20 % of the number of granules at 5 h. There was no clear deposition of granules in other components. At 5 h, radioactivity was measured at 1.799 µg Eq/g in the stomach and 0.172 µg Eq/mL in plasma. After 24 h, radioactivity had decreased to 0.584 µg Eq/g in the stomach and 0.078 µg Eq/mL in plasma.Vonoprazan selectively accumulates in gastric parietal cells in the mucosal layer of the rat stomach after intravenous administration.

Vonoprazan exhibits a more potent, rapid, and longer-lasting inhibitory effect on gastric acid secretion than proton pump inhibitors; however, whether it is more effective than PPI for treating endoscopic submucosal dissection (ESD)-induced artificial ulcers remains controversial. This study aimed to assess and compare the effects of vonoprazan and lansoprazole for treating ESD-induced artificial ulcers. This prospective, randomized controlled trial enrolled 149 patients who underwent ESD for the treatment of early gastric neoplasms from April 2015 to May 2017. They were randomly treated with either 20 mg/day vonoprazan (V group) or 30 mg/day lansoprazole (L group) orally. The primary end points were the area and shrinkage ratio of the ulcers at 4 and 8 weeks post-ESD. Data from 127 patients were analyzed, which showed that the 4- and 8-week healing ratios were not significantly different between the V and L groups (4 weeks, 16.3 vs. 25.8%; 8 weeks, 86.9 vs. 90.9%, respectively). Similarly, the shrinkage ratio, categorized as less than 90%, 90% or more but less than 100%, or 100% at 4 weeks and as less than 100% or 100% at 8 weeks were not statistically different between the V and L groups (4 weeks: 12, 41, 8 vs. 13, 41, 12, p = 0.7246; 8 weeks: 9, 52 vs. 9, 57, p = 0.8568). Delayed bleeding was also not significantly different between both the groups (5.4 vs. 5.3%; p = 0.9844). Vonoprazan is as effective as lansoprazole in treating ESD-induced ulcers.

Although proton pump inhibitors (PPIs) have been used widely, acid-related diseases are still associated with a huge burden on the health care system. Recently, the efficacy and safety of a new acid suppressant named vonoprazan in the treatment of acid-related diseases have been evaluated by a series of studies. As a novel potassium-competitive acid blocker, vonoprazan may provide reversible acid suppression by preventing K+ from binding to gastric H+/K+-ATPase. It has been clinically used for the short-term treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease and Helicobacter pylori (H. pylori) infection in Japan. The healing rate of GERD and gastric ulcers by vonoprazan is more than 95 and 90%, respectively; also, it is effective in curing PPI-resistant GERD. It increases H. pylori eradication rate to more than 88% as part of both first-line and second-line therapy. It is also effective in the eradication of clarithromycin-resistant H. pylori strains. All of these short-term studies show vonoprazan is safe and well-tolerated. As a safe and effective acid inhibitor, vonoprazan might be a novel alternative in the treatment of acid-related diseases.

Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) recently approved for Helicobacter pylori eradication therapy in Japan.To compare PPI- and P-CAP-containing triple therapy and vonoprazan-based triple therapy.Two hundred ninety-five initial subjects received a PPI-containing triple therapy; the next 125 subjects received vonoprazan-containing triple therapy. Two sequential groups received 7-day eradication regimens consisting of amoxicillin 750 mg, clarithromycin 200 mg both twice a day with standard dose PPI or vonoprazan (20 mg) each twice daily. H. pylori eradication was confirmed by a 13C-UBT. Clarithromycin susceptibility was evaluated by 23S rRNA PCR.Population cure rates with clarithromycin susceptible strains were 89.6 versus 100 % for PPI and vonoprazan therapies, respectively. Cure rates with resistant strains were 40.2 % with PPI therapy versus 76.1 % with vonoprazan triple therapy. There was no difference in side effects.Although 7-day P-CAB triple therapy was superior to 7-day PPI triple therapy, neither was highly effective, or can be recommended, in the presence of clarithromycin-resistant infections.