[Efficacy and safety of Salvianolic Acid for Injection treatment during recovery phase of ischemic cerebrovascular disease: clinical study based on single-arm objective performance criteria method].

Abstract

The clinical treatment of ischemic stroke(IS) has long been plagued by the time window and complication risks of recanalization therapies, as well as the bleeding risk of antithrombotic therapy, making it urgent to explore safe and effective new regimens. Salvianolic Acid for Injection(SAFI), a TCM preparation with neuroprotective properties and the ability to improve cerebral blood flow, lacks large-sample clinical validation regarding its systematicness, efficacy, and safety of application in IS patients. This study relied on a clinical trial based on a multicenter, prospective, single-arm objective performance criteria method(registration No. ChiCTR1900026178), enrolling 2 203 IS patients with an onset time of 7-90 d and National Institutes of Health Stroke scale(NIHSS) scores of 4-20. All patients received intravenous infusion of SAFI at dose of 100 mg per day for 14 consecutive days. The primary efficacy indicator was the proportion of patients with a modified Rankin scale(mRS) scores of 0-1 at 90 d after treatment(preset target value of 35%). Secondary efficacy indicators include the proportion of patients with mRS scores recovers to 0-1 at 28 d after treatment, the comparison of NIHSS scores at 7, 14 d after treatment with the baseline, the proportion of patients with Barthel index(BI) scores≥75 at 7, 14, 28, and 90 d after treatment, and the comparison of MMSE scores with the baseline. The incidence, severity, and drug correlation of adverse events were evaluated via vital sign monitoring, laboratory examinations, etc. The binomial test(one-sided α=0.025) was used for primary endpoint analysis, and the 95%CI was calculated by the Clopper-Pearson. RESULTS:: show that among 2 127 patients who completed the trial, 47.91% of these patients(95%CI[45.77%, 50.06%]) achieve the primary endpoint, which is significantly higher than the preset objective value(P<0.000 1). NIHSS scores of patients decrease significantly from baseline scores of(6.57±3.20) to(4.62±3.33) at 14 d after treatment(P<0.000 1), with 23.79% of patients achieving scores improvement of ≥4 points or scores of 0-1. The proportion of patients with BI scores ≥75 increases from the baseline of 41.18% to 74.52% at 90 d after treatment(P<0.000 1), and MMSE scores rises from baseline scores of(22.16±8.03) to(23.95±7.38) at 90 d after treatment(P<0.000 1). In terms of safety, the incidence rates of adverse events and serious adverse reactions are 27.49% and 3.19%, respectively, with no fatal event reported. This study confirmed that SAFI can significantly improve neurological function, capabilities of daily living, and cognitive function in patients with mild to moderate IS at 7-90 d after onset, with a favorable safety profile. The trial design combining single-arm and objective performance criteria method employed in this study provides an innovative paradigm for the clinical evaluation of TCM injections and offers high-quality evidence for the clinical treatment of IS.