Effect and Safety of Hydroxysafflor Yellow A for Injection in Patients with Acute Ischemic Stroke of Blood Stasis Syndrome: A Phase Ⅱ , Multicenter, Randomized, Double-Blind, Multiple-Dose, Active-Controlled Clinical Trial

Objective: To assess the effect and safety of Hydroxysafflor Yellow A for Injection(HSYAI) in treating patients with acute ischemic stroke(AIS) and blood stasis syndrome(BSS). Methods: A multicenter, randomized, double-blind, multiple-dose, active-controlled phase Ⅱ trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups(25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group(Dengzhan Xixin Injection(灯盏细辛注射液, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale(mRS) score 1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale(NIHSS) score 1, Barthel Index(BI) score 95, and BSS score reduced 30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment. Results: Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium-and high-dose HSYAI groups with m RS score 1 at days 90 after treatment were significantly larger than the control group(P0.05). The incidences of favorable outcomes of NIHSS and BI at days 90 after treatment as well as satisfactory improvement of BSS at days 30 and 60 after treatment in the medium-and high-dose HSYAI groups were all significantly higher than the control group(P0.05). No significant difference was reported among the 4 groups in any specific adverse events(P0.05). Conclusions: HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium(50 mg/d) or high dose(75 mg/d) might be the optimal dose for a phase Ⅲ trial.(Registration No. ChiCTR-2000029608)