Real-world functional outcomes of sovateltide as an adjunct to standard therapy in acute ischemic stroke: A prospective observational study

Acute ischemic stroke (AIS) remains a leading cause of long-term disability and mortality worldwide. Current therapeutic strategies primarily focus on reperfusion, with limited options to enhance neuroregeneration and functional recovery. Sovateltide, a selective endothelin-B receptor agonist, has demonstrated neuroprotective and neurorestorative potential in preclinical and early clinical studies. This study aimed to assess real-world neurological and functional outcomes in AIS patients receiving standard therapy, with a subgroup additionally receiving sovateltide as part of routine clinical care. A prospective real-world observational study was conducted over 6 months (April-September 2025) in the Neurology Department of PSG Hospitals, Coimbatore. During routine clinical care, patients presenting with AIS within 24 hours of symptom onset were consecutively identified. Based on the treatment they naturally received as part of standard clinical decision-making, patients were classified into 2 groups: standard therapy alone (n = 40) or standard therapy plus intravenous sovateltide (n = 40). Sovateltide (0.3 µg/kg) was administered as part of routine care in 3 doses on Days 1, 3, and 6. Neurological and functional outcomes were assessed using the NIH Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) at baseline and at 90-day follow-up by trained outcome assessors blinded to treatment classification. A total of 80 patients were included, with 40 receiving standard therapy and 40 receiving adjuvant therapy with sovateltide. Stroke severity assessed by the NIHSS was comparable between groups at baseline. Across follow-up, NIHSS scores decreased in both groups, with the sovateltide group showing greater numerical reductions at 60 days (P = .040) and 90 days (P = .006). Functional recovery patterns assessed using the BI indicated higher median scores in the sovateltide group at 30 days (P = .0429), 60 days (P = .0350), and 90 days (P = .0376). mRS scores also declined over time in both groups, with the sovateltide group demonstrating more favorable distributions at 30 days (P = .0413), 60 days (P = .0246), and 90 days (P = .0064). Within-group analyses showed significant improvements in NIHSS, BI, and mRS across all time points for both cohorts (P < .0001). These findings represent observed differences only and do not indicate causality. In this real-world observational study, patients who received sovateltide as part of routine care showed more favorable trends in neurological and functional outcomes over 90 days compared with those receiving standard therapy alone. These findings represent associations only and do not establish causality. The results offer preliminary real-world insights into the use of sovateltide in AIS, and larger randomized controlled trials are required to determine its independent therapeutic role and to confirm these observations. © © 2026 the Author(s). Published by Wolters Kluwer Health, Inc.