Supplementary Material for: Ruyi Zhenbao Tablet and Baimai Ointment Therapy in Acute Ischemic Stroke: A Study Protocol for a Multi-center, Randomized, Double-blinded, and Parallel Controlled Trial

Introduction: Stroke is characterized by high incidence, recurrence rate, and mortality. Patients with acute is-chemic stroke (AIS) who are ineligible for acute revascularisation therapy require more effective medication treatments. A previous clinical study showed that Ruyi Zhenbao tablets and Baimai ointments might be effective against AIS; however, high-quality clinical evidence supporting their application in AIS is lacking. To explore the efficacy of the two classic Tibetan medicines in the treatment of AIS, a randomized clinical trial will be conducted in patients with AIS who are not eligible for thrombolytic treatment. Methods: A prospective, randomized, multiple-center, double-blinded, placebo-controlled, and parallel-group trial will be conducted. We shall randomize 480 eligible participants to either the intervention or the control group. The distribution ratio of each group will be 1:1:1:1, including 120 patients each in the dual-medication group, the Baimai ointment group, the Ruyi Zhenbao tablet group, and the placebo group. Participants will be treated with medication for 8 weeks, and they will receive three follow-up visits: at 4 weeks(D29), 8 weeks(D56), and 90 days (D90) after commencing treatment. The primary outcome will be D90 change in the simplified Fugl-Meyer score from baseline to post-treatment. The secondary outcomes are as follows:D29 change of simplified Fugl -Meyer score from baseline to post-treatment; Proportion of participants whose D29 NIHSS scores decreased by four or more points from baselineD90 proportion of subjects with mRS score of 0-2 (inclu-sive); D90 proportion of subjects with Barthel index score ≥95; D90 incidence of cardiovascular and cerebro-vascular events. Safety endpoint includes:Mortality within 90 days;Proportion of subjects with adverse events/ serious adverse events within 90 days. Conclusion: This research protocol lays a solid groundwork for its practical execution. This study is poised to serve as a reference for other Tibetan medicine researchers, contributing to the reduction of stroke-related expendi-tures globally and, in turn, benefiting a broader population of stroke patients