Background: Adjunct therapies are needed for patients with acute ischemic stroke who fare poorly, despite standard-of-care endovascular thrombectomy (EVT). RESCUE (A Randomized, Blinded, Placebo-Controlled, Parallel Group Design to Determine the Safety of RNS60 in Large Vessel Occlusion Stroke Patients Undergoing Endovascular Thrombectomy) tested the cytoprotective experimental drug RNS60 in patients with acute ischemic stroke, adjunct to EVT with or without prior standard-of-care thrombolytic treatment.

Methods: RESCUE, a randomized, placebo-controlled, double-blind, phase 2 study, enrolled 83 participants eligible for EVT within 24 hours since last known well, 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. A post hoc analysis evaluated safety and efficacy in a subpopulation of 62 participants enrolled within 12 hours since last known well. Efficacy end points included modified Rankin Scale score, post-EVT infarct growth, National Institutes of Health Stroke Scale score, Barthel Index score, EuroQoL, and duration of hospitalization and discharge disposition.

Results: In this subpopulation, RNS60 1.0 mL/kg per hour was generally safe and well tolerated and reduced post-EVT infarct growth compared with placebo (least squares mean difference, 22.2; P=0.05). Of the participants treated with RNS60 1.0 mL/kg per hour, 72.2% achieved a 90-day modified Rankin Scale score of 0 to 2, and 72.2% achieved a Barthel Index score ≥95, compared with 36.8% (for both measures) of those receiving placebo, although the differences were not statistically significant (P=0.09 for both modified Rankin Scale and Barthel Index scores). Consistent but smaller differences to placebo were seen in the RNS60 0.5 mL/kg per hour group, which suggests a dose-dependent effect of RNS60. Participants in the RNS60 1.0 mL/kg per hour group were also released earlier from the hospital than those in the placebo group (mean [SD]: 6.0 [5.10] days versus 10.8 [6.84] days; mean difference [SE], −4.8 [1.99]; P=0.02). Final infarct volumes at 48 hours post-EVT correlated with modified Rankin Scale scores at day 90 for RNS60 1.0 mL/kg per (Pearson r=0.65; P=0.005) and placebo (r=0.65; P=0.007).

Conclusions: Effects of RNS60 were favorable compared with placebo in the analyzed subpopulation, warranting further investigation in this population.