This randomized, placebo-controlled, double-blind, dose-escalation clinical trial in acute ischemic stroke patients was designed to demonstrate maximum tolerated dose, characterize adverse events (AEs), and explore clinical outcomes when intravenous DDFPe was used as neuroprotection. Intravenous DDFPe appears to be safe at all doses tested. Clinical improvements in NIHSS score and mRS were significant but compromised by small sample size.
The results of a randomized, blinded, placebo-controlled clinical trial testing intravenous DDFPe in patiets with acute ischemic stroke are presented. 6 patients received placebo, six patients received 0.05 ml/kg of DDFPe every 90 minutes for three doses, six patients received 0.10 ml/kg of DDFPe every 90 minutes for three doses, and six patients received 0.17 ml/kg of DDFPe every 90 minutes for three doses. IV DDFPe appeared safe at all tested doses. No MTD was defined. Exploratory Aims suggest that early DDFPe treatment improves NIHSS quickly and high dose DDFPe patients suggested improved outcomes. Larger trials are warranted.
Dodecafluoropentane emulsion (DDFPe) is a novel nanotechnology for oxygen delivery with therapeutic potential for hemorrhagic shock and/or traumatic brain injury (TBI). DDFPe demonstrates efficacy at smaller doses than previously tested perfluorocarbon oxygen therapeutics. This smaller dose potentially eliminates toxicities exhibited by previous oxygen therapeutics, while anti-inflammatory properties of DDFPe may alleviate damage from ischemia reperfusion injury. This mini-review summarizes our progress in developing a battle-field ready product to prevent combat death due to hemorrhagic shock and/or TBI.
This poster was presented at the National Neurotrauma Society Meeting, Snowbird, Utah, on July 11th, 2017. In this swine model of TBI, administration of DDFPe resulted in lower injury scores for spongiosis and ischemic neurons in the cerebellum as well as a decreased number of Fluoro-Jade B positive purkinje cells. This data suggests that DDFPe may play a role in mitigating secondary brain damage.
This study administered nine dosing regimens of DDFPe into New Zealand White Rabbits, the same species used for the majority of pre-clinical studies in stroke. The study describes DDFP distribution in brain, kidney, liver, spleen, and lung. The total clearance of DDFP was consistent with previous reports showing 98% of DDFP is cleared within 2 h of administration.
This book, published in 2017, is a very timely compilation of cutting-edge aspects of neuroprotective therapy for ischemic stroke. This book is divided into four sections, ranging from historical aspects of neuroprotection right through to the latest aspects of clinical trial design. Chapter 26 on oxygen carriers was authored by NuvOx co-founder, Jennifer Johnson, PhD. A link to excerpts is here.
Dodecafluoropentane emulsion (DDFPe), an advanced oxygen transport drug, given IV at 90-min intervals maintains viability in the penumbra during cerebral ischemia in the standard rabbit anterior stroke model. This study investigated shortened dosage schedules of DDFPe in nonstandard posterior strokes following occlusions of the posterior cerebral arteries. In the standard anterior stroke group given DDFPe, the % stroke volume, neurological assessment scores, and serum glutamate were significantly decreased vs controls (p = 0.0016, 0.008, and 0.016, respectively). In the DDFPe nonstandard posterior stroke group, %SV, NAS, and serum glutamate did not differ statistically com-pared to nonstandard controls (p= 0.82, 0.097, and 0.06, respectively). In anterior strokes, DDFPe improves recovery but not in the more severe nostandard posterior strokes. Dated: 2016