Background: Despite transformational advances in reperfusion therapies, acute ischemic (AIS) stroke remains a leading cause of death and long-term disability, underscoring a critical unmet need for adjunctive cerebroprotective strategies. RNS60, oxygen supersaturated in saline with a patented technology, was tested as a drug candidate for such an adjunctive therapy. Methods: RESCUE, a proof-of-concept phase 2 trial, showed that RNS60 treatment for 48h starting during endovascular thrombectomy (EVT) in 82 participants with large vessel occlusion enrolled within 24h since symptom onset was safe, reduced post reperfusion infarct growth by 47% at 48h (nominal p<0.05) and achieved numerical improvements in prespecified clinical endpoints at Day 90 compared to placebo. Additional post-hoc analyses were conducted in participants enrolled within 12h of symptom onset (~75% of ITT). Results: The subgroup enrolled within 12h showed a consistent but larger response compared to the ITT. Both infarct volume and post-EVT infarct growth at 48h were lower in the RNS60 group compared to dose matched placebo. As in the ITT population, the infarct growth difference reached statistical significance, 20.1±10.4 mL in high dose (1.0 mL/kg/h) RNS60 vs. 42.2±10.0 mL in placebo (p=0.04). The post-thrombectomy infarct growth at 48h correlated with the mRS at 90 days, suggesting the usefulness of this imaging biomarker (Figure 1). In the RNS60 high dose group, 72% of subjects had an mRS of 0-2 or BI ≥95 compared to 37% in the placebo group at Day 90. The LS mean±SE of mRS was 2.27±0.54 for RNS60 compared to 3.4±0.54 for placebo (p=0.01), LS mean±SE of BI was 71.15±9.8 for RNS60 and 46.38±9.65 for placebo (p=0.01). Of the high dose RNS60 group, 56% responded to the treatment with a combination of mRS 0-2 and BI ≥95 and NIHSS 0-1 on Day 90 compared to only 31% in the placebo group. Consistently, the length of hospital stay was reduced by a mean of 4.8 days (p=0.02) in the RNS60 high group and more participants (55% vs. 21%, p=.03) in this group were released to home rather than other care facilities compared to placebo. Conclusion: RNS60 treatment at the 1.0 mL/kg/h dose level shows the promise of an effective cerebroprotective therapy. The effect was more pronounced in the subgroup enrolled within 12h since symptom onset. Post-reperfusion infarct growth at 48h correlated with 90-day clinical outcomes in this subgroup.
Ghosh et al. (Thu,) studied this question.