Adding Acotiamide to Gastric Acid Inhibitors Is Effective for Treating Refractory Symptoms in Patients with Non-erosive Reflux Disease

Abstract

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.

Effects of Pistacia lentiscus and Coriander Triphala on Adult Gastroesophageal Reflux Disease: A Randomized Double-Blinded Clinical Trial

“…It should be noted that in seven placebo-controlled trials of PPI therapy, the therapeutic gain for regurgitation response averaged 17% compared to placebo; this effect was more than 20% lower than that observed for heartburn (48). Yamashita et al (14) reported that adding gastric acid inhibitors to acotiamide could reduce the total reflux, liquid reflux, and proximal reflux episodes. The combination of omeprazole (20 mg/day) and baclofen showed high improvement in burning and reflux (34).…”

“…Furthermore, many patients should receive these medications for a long time or even lifelong, which causes side effects such as Clostridium difficile infections (10), kidney problems (11), hip fractures (12), and respiratory infections (13). The symptoms easily relapse after stopping PPIs (1,14). Due to the failure of conventional treatments, a growing interest has been developed in herbal medicine.…”

Effects of acotiamide on functional dyspepsia patients with heartburn who failed proton pump inhibitor treatment in Japanese patients: A randomized, double‐blind, placebo‐controlled crossover study

“…19,20 On the other hand, it has been reported that acotiamide reduced regurgitation with transient lower esophageal sphincter relaxation (TLESR) and improved esophageal clearance in healthy subjects, 38 and it ameliorated minor esophageal peristaltic abnormalities observed in healthy subjects. 39 In a recent report on acotiamide, Yamashita et al 40 Abbreviations: NS, not significant; SD, standard deviation. a Data on FD symptom scores after treatment were expressed as mean ± SD.…”

Pharmacologic treatment of GERD: Where we are now, and where are we going?

“…Evidence is limited because early studies had poor enrollment and remain incomplete. 193 Newer agents, such as relamorelin and other ghrelin agonists, are currently under development. 194 These compounds have not yet been studied in patients with both gastroparesis and GERD.…”