Impact of different domperidone dosages on reflux esophagitis treated with esomeprazole: a randomized controlled trial

Abstract

This study aimed to systematically evaluate the efficacy and safety of different doses of domperidone (DOM) combined with esomeprazole (ESM) in the treatment of reflux esophagitis, providing a basis for precise clinical medication. This prospective single-center study enrolled a total of 376 eligible patients with reflux esophagitis (intention-to-treat [ITT] population) between January 2022 and December 2024, among whom 361 completed the full treatment course (per-protocol [PP] population). A total of 361 patients were randomly divided into four groups: control group (oral ESM, n = 90), low-dose group (oral ESM + 5 mg DOM, n = 92), medium-dose group (oral ESM + 10 mg DOM, n = 91), and high-dose group (oral ESM + 15 mg DOM, n = 88), all for an 8-week duration. The primary outcome was the endoscopic remission rate at 8 weeks, defined as the achievement of Los Angeles classification grade 0 or A (ITT and PP population). Secondary outcomes (PP population) included changes in symptom scores (Gastroesophageal Reflux Disease Questionnaire, Reflux Symptom Index, Reflux Disease Questionnaire), quality of life (GERD-Health Related Quality of Life scale, EuroQol Five-Dimension Five-Level Scale), high-resolution esophageal manometry parameters, 24-hour impedance-pH monitoring indices, serum inflammatory cytokine levels, and the incidence of adverse events. The medium-dose DOM combination group demonstrated the most favorable efficacy across all key endpoints. Its endoscopic remission rate was significantly higher than that of the other three groups (P < 0.05). The results of the ITT analysis were highly consistent with the PP analysis. In the ITT population, the medium-dose group demonstrated a significantly superior endoscopic remission rate (94.68%) compared to the other three groups (P < 0.05). This finding was corroborated by the PP analysis, which also showed the optimal efficacy in the medium-dose group (97.80%). Concurrently, this group exhibited the most pronounced improvements in symptom scores and quality of life, the greatest recovery in esophageal motility parameters, the most significant reduction in all types of reflux episodes, and the greatest decrease in inflammatory cytokine levels (all P < 0.05). The high-dose group ranked second in efficacy, while the low-dose group showed superiority over the control group only in partial indicators. Although there was no significant difference in the incidence of adverse events as reported in the study, the overall event incidence and the increasing trend among different groups suggest the possible existence of a dose-response relationship, especially in the high-dose group. Based on standard esomeprazole therapy, the addition of medium-dose DOM (10 mg three times daily) synergistically improves reflux control, mucosal healing, motility recovery, and inflammatory status. This dose achieves an optimal balance between efficacy and safety, providing high-level evidence for implementing individualized and precise medication strategies in clinical practice. Although overall adverse event rates did not differ significantly among groups, a dose-dependent trend was observed. Higher doses offer no additional benefit and may increase safety concerns.

Keywords: domperidone; esomeprazole; proton pump inhibitor; reflux esophagitis.