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In this randomized, double\u2010blind, placebo\u2010controlled crossover study, the effects of adding acotiamide to treatment with proton pump inhibitors (PPI) were investigated in FD patients with heartburn who failed PPI treatment, corresponding to PPI\u2010resistant NERD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The subjects included 16 FD patients with heartburn who failed PPI treatment, and they were administered acotiamide or a placebo for 28\u00a0days. After suspending medication for 28\u00a0days, the trial drug and placebo were crossed over and administered for 28\u00a0days. Before the study began and after each administration period, high\u2010resolution impedance manometry (HRiM) was performed, and the modified frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire was administered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Postprandial fullness in the FD assessment and all modified FSSG items were significantly lower in the acotiamide group than in the placebo group. Esophagogastric junction pressure was significantly higher in the acotiamide group. The distal contractile integral (DCI) pressure and the highest DCI pressure both increased significantly in the acotiamide group. Moreover, in the acotiamide group, the frequency of abnormal primary peristalsis decreased to normal levels; complete bolus transit (CBT), an indicator of esophageal clearance, increased; and CBT time decreased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Acotiamide was considered to improve upper gastrointestinal functions not only in the stomach but also in the esophagus. Adding acotiamide to PPI therapy appears to improve upper abdominal symptoms in FD patients with heartburn who failed PPI treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13749","type":"journal-article","created":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T08:00:53Z","timestamp":1571126453000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effects of acotiamide on functional dyspepsia patients with heartburn who failed proton pump inhibitor treatment in Japanese patients: A randomized, double\u2010blind, placebo\u2010controlled crossover study"],"prefix":"10.1111","volume":"32","author":[{"given":"Yasushi","family":"Funaki","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Aichi Medical University Nagakute 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