Efficacy and safety of Hou Gu Mi Xi for peptic ulcer diseases Study protocol for a randomized controlled trial

Background: Peptic ulcer disease (PUD) is a major burden worldwide. Several challenges remain with standard Western treatment of PUD, such as persistent weakness, fatigue, and relapse. A dietary traditional Chinese medicine (TCM) formula, Hou Gu Mi Xi (HGMX), has been developed as a complementary treatment for PUD. Aims: This multicenter, double-blind, randomized controlled trial will assess efficacy and safety of HGMX in patients with PUD. Methods: Three hundred sixty eligible patients will be assigned to receive HGMX, placebo, HGMX + rabeprazole or placebo + rabeprazole for 4 weeks after 2 weeks of standard Western treatment. This first step, with a 2 x 2 factorial design, will focus on assessing the main and interaction effects of HGMX and rabeprazole on ulcer healing. Then, rabeprazole will be stopped, and HGMX will be continued for up to 1 year. The second step, with a placebo-controlled design, will compare the long-term effects of HGMX and placebo. Extended follow-up with no treatment will continue for up to 2 years. Independent and paired t tests, Pearson x 2 test and the rank-sum test will be used to compare between-group differences. The P value will be adjusted using the O'Brien & Fleming method for multiple comparisons. Expected outcomes: The primary outcomes are total efficacy rate of PUD treatment, quality of ulcer healing, and changes in spleen qi deficiency symptoms. The secondary outcomes include ulcer area, PUD recurrence, Helicobacter pylori eradication rate, gastric function, body weight, and body mass index. Adverse events (AEs), severe AEs, treatment-related AEs, and withdrawal owing to AEs will be recorded to assess treatment safety. Discussion: The trial results will provide high-quality evidence for HGMX, as a complementary therapy, for the long-term management of PUD and will be valuable for the development of related guidelines and regulations.