Abstract Body: Introduction: The involvement of ET-B receptors in neurogenesis has provided a target for treating cerebral ischemic stroke patients. Sovateltide is a highly selective ET-B receptor agonist and a synthetic analog of endothelin-1. It has shown functional recovery in animal models and patients with cerebral ischemic stroke.
Methods: Patients aged 18 to 78 years presenting up to 24 hours after the onset of symptoms with radiologic confirmation of ischemic stroke could be enrolled if with a NIHSS score of ≥6. Patients receiving endovascular therapy or with intracranial hemorrhage were excluded. Patients were randomized, with 80 patients in the sovateltide and 78 in the control group. The study drug (normal saline or sovateltide (0.3 µg/kg) was administered intravenously in three doses at intervals of 3±1 hour on days 1, 3, and 6 (total sovateltide dose of 0.9 µg/kg/day).
Results: The age, body weight, male-female ratio, NIHSS, and ASPECTS were similar between the control and the sovateltide groups. The median interval between stroke onset and the first treatment dose was 18.58 hours in the sovateltide and 19.71 hours in the control groups. In the control group, a greater (P=0.0195) number of patients received thrombolytics than in the sovateltide group. The medical history of co-morbid conditions, hypertension, diabetes, and diabetes plus hypertension was similar in the sovateltide and control groups. Patients completing 90-day follow-up were 70 in the control group and 67 in the sovateltide group. The Multivariate Imputation by Chained Equations was used to impute the missing assessments on the endpoints. The number of patients with good neurological outcomes with mRS of 0-2 (22.67%; p=0.003) and NIHSS of 0-5 (17.05%; p=0.011) at 90 days were more in the sovateltide than in the control group. The BI scores of 90-100 at 90 days also showed a numerically greater number of patients (13.91%; p=0.080) in the sovateltide than in the control group. An improvement of ≥2 points on the mRS was observed in 51.28% and 72.50% of patients in the control and sovateltide groups, respectively (p=0.006). The ordinal shift in mRS from 0-2 showed an absolute increase of 22% in the favorable outcome of sovateltide compared to the control group. The adverse events were not related to sovateltide.
Conclusions: Sovateltide produced significant improvement in neurological outcomes at 90 days post-treatment in acute cerebral ischemic stroke patients and suggests imminent efficacy trials.