Neuroprotective therapies have been particularly challenging to translate from experimental models to the clinical setting despite abundant promising mechanistic and pre-clinical research. Narrow therapeutic windows requiring very early administration are thought to be a leading reason for the failure of previous clinical trials of neuroprotection in survivors of cardiac arrest. In this project, we will creatively re-design the implementation of a clinical trial of a very early neuroprotective intervention in patients with out of hospital cardiac arrest (OHCA). Just as bystander CPR and public automated defibrillators have increased rates of resuscitation from cardiac arrest, we will leverage bystanders and first responders (police or firefighters) to accomplish clinical trials in which a study intervention can be administered to victims of OHCA prior to EMS arrival or return of spontaneous circulation. The overarching goal of this proposal is to create a framework for investigating new therapies for neuroprotection. The specific objective of this project is to discover how such solutions will work given regulatory and operational barriers to a clinical trial of first responder and layperson administered intranasal insulin in patients with OHCA. The project will integrate with both the Basic Science and Population Science Projects in this SFRN application. The lessons learned will be generalizable to the study of other putative neuroprotective agents requiring early administration, and this could even support a platform methodology allowing study of multiple agents in the future. Our primary hypothesis is that a clinical trial of very early neuroprotective drug delivery by bystanders or first responders during OHCA is feasible. The parameters of feasibility to be explored will include four specific aims addressing: 1) acceptability to regulators, 2) performance by first responders and laypersons, 3) determination of maximum tolerated dose of intranasal insulin, and 4) estimation of sample size and trial operating characteristics under a variety of proposed scenarios. The results of this project will determine the feasibility and potential value of performing a double-blind randomized clinical trial of very early drug delivery during CPR by bystanders or first responders.
|Program type||Strategically Focused Research Network|
|Effective start/end date||07/01/2019 → 06/30/2023|