Randomized, Proof-of-Concept Trial (RESCUE) of RNS60 as an Adjunct Therapy in Acute Ischemic Stroke

Abstract

Background: Despite significant improvements in early reperfusion, many patients with acute ischemic stroke with large vessel occlusion experience poor outcomes, which indicates a clear need for adjunct therapies. RNS60 is a proprietary combination of oxygen supersaturated in saline with cerebroprotective and immunomodulatory effects. RNS60 showed therapeutic promise in rodent and nonhuman primate models of acute ischemic stroke. RESCUE (A Randomized, Blinded, Placebo-controlled, Parallel Group Design to Determine the Safety of RNS60 in Large Vessel Occlusion Stroke Patients Undergoing Endovascular Thrombectomy) was the proof-of-concept trial testing adjunctive treatment with RNS60 in patients with acute ischemic stroke with large vessel occlusion undergoing endovascular thrombectomy with or without prior treatment with an intravenous thrombolytic.

Methods: This randomized multicenter, placebo-controlled, double-blind, phase 2 study enrolled 82 participants, assigned 1:1:1 to 48-hour infusion of RNS60 0.5 mL/kg per hour, RNS60 1.0 mL/kg per hour, or placebo 1.0 mL/kg per hour, and followed for 90 days. Rates of serious adverse events and mortality were the primary end points. Efficacy end points included the modified Rankin Scale score, infarct volume growth, National Institutes of Health Stroke Scale, worsening of stroke, Barthel Index, and the EuroQoL health-related quality of life scale.

Results: The RNS60 groups met the primary end points with similar rates of serious adverse events (33.3%, 25.0%, and 28.6%) and fewer deaths (6.7%, 8.3%, and 14.3%) across RNS60 0.5 mL/kg per hour, RNS60 1.0 mL/kg per hour, and placebo, respectively. The RNS60 1.0 mL/kg per hour group showed reduced infarct growth by 47% at 48 hours post-endovascular thrombectomy (21.4 mL [interquartile range, 5.0-29.1] versus 40.6 mL [interquartile range, 6.3-62.3]; P<0.05). No statistically significant differences were observed in other efficacy end points, but a higher proportion of participants in the RNS60 1.0 mL/kg per hour group had reduced disability (modified Rankin Scale score of 0-2) and functional independence (Barthel Index ≥95) on Day 90.

Conclusions: RNS60 was safe and well tolerated. The RNS60 1.0 mL/kg per hour reduced infarct growth after endovascular thrombectomy compared with placebo. This suggests a benefit warranting investigation in a larger, appropriately powered trial.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04693715.

Keywords: RNS60; cytoprotective; drug therapy; humans; ischemic stroke; thrombectomy.