Efficacy and Safety of Chinese Herbal Medicine in Patients with Acute Intracerebral Hemorrhage: Protocol for a Randomized Placebo-Controlled Double-Blinded Multicenter Trial

Abstract

Background: The popular traditional Chinese medicine (TCM) compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) through effects on brain edema, hematoma absorption, and the immune system. Aim: The aim of this study is to assess whether FYTF-919 is safe and effective as compared to matching placebo treatment in patients with acute ICH. Methods: The ongoing Chinese Herbal medicine in patients with Acute INtracerebral hemorrhage (CHAIN) is a multicenter, prospective, randomized, double-blind placebo-controlled trial of FYTF-919 in patients with acute ICH at 20-30 hospital sites in China. Eligible ICH patients presenting within 48 h after symptom onset are randomly allocated to receive either FYTF-919 (100 mL per day x 28 d, oral) or matching placebo. A sample size of 1504 patients is estimated to provide 90% power (α 0.05) to detect a ≥20% improvement in average utility-weight scores on the modified Rankin scale (UW-mRS) assessed at 90 days, with 6% non-adherence, and 10% lost to follow-up. The primary efficacy outcome is UW-mRS at 90 days. Secondary outcomes include binary measures of the mRS, neurological impairment on the National Institute of Health Stroke Scale, and health-related quality of life on the EuroQol EQ-5D-3L scale at different time points over 12 months of follow-up. The key safety measure is serious adverse events. Conclusion: CHAIN is on schedule to provide reliable evidence over the benefits of a popular herbal TCM for the treatment of acute ICH. Trial registration: Clinicaltrial.gov NCT05066620.