Primary outcomes

The two primary outcomes are the response rate based on overall treatment effect (OTE) and the elimination rate of all three cardinal symptoms: postprandial fullness; upper abdominal bloating; and early satiation (no symptoms) at the end of treatment (four weeks after randomization) [26].

When assessing OTE, outcome assessors will evaluate patients using a 7-point Likert scale. The question is “How were your gastric symptoms during the past week in comparison with the baseline period?”, which closely resembles the way physicians evaluate treatment benefit in clinical practice. The answers will include “extremely improved,” “improved,” “slightly improved,” “not changed,” “slightly aggravated,” “aggravated,” and “extremely aggravated” [26]. Patients who answer “extremely improved” or “improved” will be considered as responders. Although there is no universally accepted primary outcome established for therapeutic trials in FD, OTE is a frequently used outcome [27], which has been used as the primary outcome in several trials [28–30].

The elimination rate of three cardinal symptoms was added as another primary outcome. Because the U.S. Food and Drug Administration has argued against the use of OTE as a single primary outcome for its recall bias. After trial commencement, the Data and Safety Monitoring Board (DSMB) suggested that we could use combined primary outcomes for our study. Similarly, the pattern of two primary outcomes was adopted in a study evaluating acotiamide in FD [26]. The elimination rate is based on the severity of dyspepsia symptoms [31] and is defined as the proportion of patients whose scores of postprandial fullness, upper abdominal bloating, and early satiation all decline to 0 [26].

Acupuncture will be considered as an effective therapy, only if both primary outcomes achieve significant difference to avoid type I error accumulation. All protocol amendments are described in detail in Additional file 2.