Abstract TMP17: Dodecafluropentane Emulsion in Acute Ischemic Stroke, a Phase One Randomized and Controlled Trial

Abstract

Introduction: In Acute Ischemic Stroke (AIS) the effective therapeutic window remains very short for the vast majority of patients and severely limits those who qualify for acute therapy. The oxygen transporting nanodroplet Dodecafluoropentane emulsion (DDFPe) (NuvOx Pharma, Tucson, AZ) given IV within 3h of onset can reduce AIS symptoms and stroke volumes markedly in animal studies and may widen the window significantly for therapy. We conducted a randomized, placebo-controlled, double blinded, dose escalation AIS trial to demonstrate the Maximum Tolerated Dose, characterize adverse events and explore impacts on acute NIHSS values and long-term outcomes. Methods: AIS patients with NIHSS of 2-20 were randomized to either 3 doses of IV DDFPe or placebo, one every 90 minutes, starting within 12 hours of symptom onset. Doses were given as soon as possible between unmodified standard stroke care elements. Each dose cohort included 8 patients, with 2 receiving placebo and 6 DDFPe. Primary outcomes were SAEs, AEs, NIHSS values, and mRS. Results: No Dose Limiting Toxicities were encountered and no maximum dose defined. One unrelated delayed death occurred in the DDFPe group and one in the placebo group while SAEs and AEs were similar. Early DDFPe treatment of any dose had better NIHSS values at 4.5h than late doses, p=0.03. In high dose DDFPe mRS outcomes suggested improvement, p=0.01 at 30 days and p=0.03 at 90 days. Conclusions: IV DDFPe appeared safe at all doses. Early DDFPe treatment showed NIHSS improvements and high dose DDFPe patients suggested improved outcomes. Larger trials are warranted.