Statistical Analysis Plan of a Decentralized, Randomized, Double-Blind, Placebo-Controlled Trial of Gengnianshou Granules for Menopausal Vasomotor Symptoms (Preprint)

BACKGROUND Menopausal vasomotor symptoms (VMS) significantly impact women's daily activities and quality of life. The Gengnianshou (GNS) formula, derived from traditional herbal medicine clinical practice, has shown potential efficacy in alleviating menopause-related VMS and other associated symptoms. OBJECTIVE Before unblinding and trial database lock, we describe a prespecified statistical analysis plan (SAP) to define the study's analytical framework and statistical methods in advance, thereby minimizing the risk of selective outcome reporting and data-driven analyses. METHODS A multicenter, double-blind, randomized, placebo-controlled, decentralized clinical trial (DCT) is designed to evaluate the efficacy of GNS granules versus placebo in improving menopausal VMS. A total of 222 participants were randomly assigned to receive either 12 weeks of GNS granules or placebo. Clinical assessments were conducted at baseline and at Weeks 4, 8, and 12, with a post-treatment follow-up at week 24. The primary efficacy endpoint was the mean change from baseline in the daily frequency of VMS at Week 12. Secondary efficacy endpoints included changes from baseline in hot flash severity and bother scores; Hot Flash–Related Daily Interference Scale (HFRDIS) scores; Kupperman Menopausal Index (KMI) scores; Generalized Anxiety Disorder-7 (GAD-7) scores; Patient Health Questionnaire-9 (PHQ-9) scores; Pittsburgh Sleep Quality Index (PSQI) scores; and Chinese Medical Syndrome Scores (CMSS). Safety events and objectively measured laboratory parameters were recorded. RESULTS At the time of SAP finalization, participant recruitment and follow-up had not yet started. The first participant was enrolled on July 24, 2024, and the last participant completed the 24-week follow-up on December 12, 2025. No efficacy data have been unblinded or analyzed to date. All study endpoints will be analyzed after database lock in a single prespecified analysis, with final statistical analyses anticipated in April 2026. CONCLUSIONS This study adopts a decentralized randomized controlled trial framework in a menopausal population, with data collected using a hybrid approach based on participant preference. CLINICALTRIAL Chinese Clinical Trials.gov ChiCTR2200058917 Registered on April 19, 2022 (http://www.chictr.org.cn).