Acotiamide Hydrochloride Hydrate

We have determined that the impaired accommodation of the lower esophageal sphincter (LES) underlies the pathogenesis of esophagogastric junction outflow obstruction (EGJOO). We have also found that acotiamide may treat EGJOO by improving impaired LES accommodation. The effects of acotiamide in patients with EGJOO need to be further confirmed in a prospective study.

This trial is a multicenter, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of acotiamide (300 mg/day or 600 mg/day) with those of a placebo in the treatment of patients with EGJOO. The primary endpoint will be the proportion of patients who report an improvement in symptom of food sticking in the chest after 4 weeks of treatment period 1. The secondary endpoints will be the proportion of patients with normalized integrated relaxation pressure (IRP), the value of change from baseline in the distal contractile integral, basal LES pressure, EGJOO-quality of life score, Gastrointestinal Symptom Rating Scale, and the correlation between IRP and each symptom score. During the 2-year trial period, 42 patients from five institutions will be enrolled.

This trial will provide evidence to clarify the efficacy and safety of acotiamide as a treatment for patients with EGJOO. Acotiamide might help improve the quality of life of patients with EGJOO and is expected to prevent the progression of EGJOO to achalasia.

This study was approved by the Institutional Review Board (IRB) of Kyushu University Hospital as well as the local IRBs of the participating sites for clinical trials and registered in the Japan Registry of Clinical Trials (jRCT: 2071210072). The registration date is on October 11, 2021.

Acid suppression improves dyspepsia symptoms but the efficacy of vonoprazan for functional dyspepsia remains unclear. The aim of this study is to evaluate the effectiveness of vonoprazan therapy for functional dyspepsia without heartburn.

Patients receiving vonoprazan 10 mg once daily or acotiamide 100 mg three times daily for more than one month were included and retrospectively reviewed. Functional dyspepsia was diagnosed based on the ROME IV criteria. Patients with heartburn were excluded. Eighty-five patients were divided into vonoprazan (n=48) and acotiamide (n=37) groups.

There were no significant differences at baseline between the vonoprazan and acotiamide groups. The functional dyspepsia score significantly improved in both groups (p<0.001). The degree of score reduction (55% vs 59%, p=0.559) and the resolution rates (21% vs 30%, p=0.345) were similar. Epigastric pain and postprandial distress scores were significantly improved in both groups, and the degree of improvement of each score was similar. Constipation and diarrhea scores were significantly improved in both groups, and the degree of improvement similar.

These preliminary results suggest that vonoprazan is effective for the treatment of functional dyspepsia without heartburn in the short-term, with results similar to acotiamide therapy.