Efficacy and safety of Qingre Huatan Formula for the prevention of early neurological deterioration in patients with acute ischemic stroke (QUIET): rationale and design for a randomized double-blind placebo-controlled study

Background: Early neurological deterioration (END) remains challenging despite guideline-based treatments in patients with acute ischemic stroke (AIS). To date, limited evidence has been established to prevent END. Therefore, this study aims to determine whether Qingre Huatan Formula (QHF) initiated within 48 h of stroke onset prevents END in AIS patients compared with placebo. Methods: The Qingre Huatan Formula for the Prevention of Early Neurological Deterioration in Acute Ischemic Stroke (QUIET) trial is a randomized, placebo-controlled, double-blind, parallel-group pilot study. Seventy-two eligible patients with AIS within 48 h of symptom onset will be randomly (1:1) assigned to receive either QHF or placebo treatment for 10 days and will subsequently be followed up to 90-days. The primary outcome is the proportion of END within 7 days of stroke onset, defined as a National Institutes of Health Stroke Scale (NIHSS) score increase of ≥2 points. Secondary outcomes mainly include the change in NIHSS score from baseline to 10 days after randomization, and the proportion of patients achieving a good functional outcome (modified Rankin Scale score ≤ 2). Discussion: This trial will provide valuable evidence for the efficacy and safety of traditional Chinese medicine for END in AIS patients. Clinical trial registration: https://register.clinicaltrials.gov, identifier NCT06857487 (registered on February 27, 2025).