Efficacy and safety of neuromodulators combined with proton pump inhibitors for non-erosive reflux disease: A randomized clinical trial

Figure 1 The protocol of the study. Gastroesophageal reflux disease questionnaire scores were collected every 2 weeks during the study. Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item scale, Pittsburgh Sleep Quality Index, Gastroesophageal Reflux Disease Health-Related Quality of Life were collected at baseline, week 2 and week 12. Medication possession ratio was calculated at week 2. Cost-effectiveness analysis was calculated at week 12. CEA: Cost-effectiveness analysis; GAD-7: Generalized Anxiety Disorder 7-item scale; GerdQ: Gastroesophageal Reflux Disease Questionnaire; GERD-HRQL: Gastroesophageal Reflux Disease Health-Related Quality of Life; PHQ-9: Patient Health Questionnaire-9; PSQI: Pittsburgh Sleep Quality Index.

Figure 2 Workflow of randomization and treatment procedures of enrolled patients. ITT: Intent-to-treat; PP: Per-protocol; FM: Flupentixol-melitracen; LPZ: Lansoprazole; P + LPZ: Lansoprazole plus placebo.

Figure 3 Primary efficacy outcomes. Comparison of treatment response rate in intent-to-treat populations at week 2. Lansoprazole plus placebo: 51/82 (62.2%, 95%CI: 51.4%-71.9%); flupentixol-melitracen + lansoprazole: 71/82 (86.6%, 95%CI: 77.6%-92.3%). FM: Flupentixol-melitracen; LPZ: Lansoprazole; P + LPZ: Lansoprazole plus placebo.

Figure 4 Treatment satisfaction of patients at week 2. FM: Flupentixol-melitracen; LPZ: Lansoprazole; P + LPZ: Lansoprazole plus placebo.

Figure 5 Scatter plot of incremental cost-effectiveness probability sensitivity analysis (n = 1000). The fourth quadrant indicated that the flupentixol-melitracen + lansoprazole regimen is an advantageous solution (with good performance and low cost).