Dengzhanxixin Injection for Acute Ischemic Stroke after Reperfusion Therapy: A Double-blind, Placebo-controlled, Multi-center Clinical Trial

<h2>ABSTRACT</h2><h3>Background</h3> Revascularization for acute ischemic stroke (AIS) can salvage at-risk brain tissue, but reperfusion injury may reduce their benefits. This study aims to evaluate the efficacy and safety of Dengzhanxixin (DZXX) injection in AIS patients receiving reperfusion therapy. <h3>Methods</h3> The DAISY (Dengzhanxixin Injection for Acute Ischemic Stroke Receiving Reperfusion TherapY) is a multicenter, randomized, double-blind, placebo-controlled, dose-exploration clinical trial. AIS patients who received reperfusion therapy were randomly assigned in a 1:1:1 ratio: high-dose (80 mg per day) DZXX injection, low-dose (40 mg per day) DZXX injection, and placebo, for 10-14 consecutive days. The primary efficacy outcome was the proportion of participants with modified Rankin Scale (mRS) score (0-1) at 90 days. The safety outcome was any adverse event within 90 days after treatment. Results Between September 2022 and August 2023, a total of 246 patients from 17 centers were enrolled, with 78 assigned to high-dose group, 89 to low-dose group, and 79 to placebo group. At 90-days, the proportion of participants with a mRS score of 0 or 1 was 78.21% in high-dose, 77.53% in low-dose, and 65.82% in placebo (high-dose <i>vs.</i> placebo, OR, 1.85, 95% CI, 0.91 to 3.77, <i>P</i>=0.11; low-dose <i>vs.</i> placebo, OR, 1.75; 95% CI, 0.88 to 3.48, <i>P</i>=0.09). No significant differences observed in adverse events among three groups (<i>P</i>=0.154). Conclusion DZXX injection demonstrated a trend toward improved functional outcomes at 90-days, but the differences were not statistically significant. It would be safe for patients with AIS undergoing reperfusion therapy without increasing the risk of bleeding. Trial Registration ClinicalTrials.gov, NCT05700097