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.
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
DDFPe nanodroplets are exceptional oxygen transporters and can protect ischemic brain in stroke models 24 h without reperfusion. Current stroke therapy usually fails to reach patients because of delays following stroke onset. We tested using DDFPe to extend the time window for tissue plasminogen activator (tPA). Longer treatment windows will allow more patients more complete stroke recovery. We test DDFPe to safely extend the time window for tPA thrombolysis to 9 h after stroke. Dated: 2015
Previous data collected on 195 New Zealand White male or female rabbits with permanent occlusion of the cerebral arteries with two to three 700-900 micron diameter spheres was further reviewed to determine incidence of mortality in all controls and DDFPe treatment groups. The conclusion is that increasing the number of DDFPe applications was significant in reducing the incidence of premature death in a model of permanent ischemic stroke and extending survival to scheduled sacrifice. This new perfluorocarbon has previously demonstrated decreased stroke volume in the rabbit stroke model and now further indicates its ability to significantly reduce the incidence of death.
Abstract - Animal studies have repeatedly shown Dodecafluoropentane emulsion (DDFPe) neuroprotection in ischemic strokes in the anterior circulation; however, when a posterior vessel is also occluded, the intricate cerebral dynamics may be altered. Many studies have used standard anterior circulation occlusions as their stroke model, but approximately 20% of ischemic strokes involve the nonstandard posterior circulation. Animals in the non-standard group that were given both anterior and posterior strokes showed no statistically significant change in stroke volume (p=0.82) with treatment, while animals in the standard group showed statistically significant reductions in stroke volume (p=0.018) with treatment. Dated: 2015