DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Testing of Novel Prosurvival Strategies in the Setting of Prolonged Damage Control Resuscitation

Principal Investigator: ALAM, HASAN
Institution Receiving Award: MICHIGAN, UNIVERSITY OF
Program: DMRDP
Proposal Number: DM160428
Award Number: W81XWH-17-1-0701
Funding Mechanism: Prolonged Field Care Research Award - Funding Level 2 - Preclinical Research
Partnering Awards:
Award Amount: $3,000,000.00


PUBLIC ABSTRACT

Rationale: In the setting of severe bleeding and traumatic brain injury (TBI), our treatments focus on prompt control of bleeding in addition to the concept of damage control resuscitation (DCR), which has recently gained favor as a superior approach to minimize deaths on the battlefield. Currently, the Tactical Combat Casualty Care Guidelines (2014) support DCR. However, in the setting of prolonged evacuations when conventional therapies are not available for hours or days, the consequences of prolonged DCR (pDCR) remain unknown. As such, therapeutic approaches must be developed to determine the safety and applicability and enhance the effectiveness of pDCR.

Ultimate Applicability: Our goal is to develop a small volume, easy-to-use, rugged, and efficacious treatment that can minimize organ injury and prolong survival in the austere battlefield where delays in evacuation are common. This approach may allow the injured to receive definitive treatment at higher echelons of care. We hypothesize that treatment with valproic acid (VPA) and dried plasma products can reduce the adverse consequences of prolonged evacuations.

Focus Areas to Be Addressed and the Potential Impact: The proposed work directly addresses the three Prolonged Field Care Research Award Focus Areas: Focus Area 1: Understanding the clinical implications of prolonged field care (PFC) and pDCR, including characterization and mitigation of the consequences related to prolonged hypotension or hypotensive resuscitation(up to 72 hours). Focus Area 2: Develop next-generation resuscitation and stabilization methods for PFC and pDCR, including novel or improved methods for resuscitation and stabilization of casualties with combined hemorrhagic shock and acute TBI, point of injury/point of need/pre-hospital capabilities to monitor and/or stabilize acute TBI casualties, and approaches to metabolic stabilization to enable prolonged out of hospital survivability. Focus Area 3: Develop enhanced treatment of injuries during PFC and pDCR, including TBI treatments to decrease morbidity and mortality and improve immediate and long-term outcomes.

Clinical Application, Benefits, and Risks: Both VPA and dried plasma are logistically superior alternatives to current therapeutic options that exist. VPA has been in clinical use for >40 years, is cost-effective (~$40 per dose), has no special storage needs, is easily administered, and has shown no serious adverse effects in a recently concluded Phase I trial, which makes it very attractive for the austere field care environment. Dried plasma has been shown to be as effective as fresh frozen plasma in models of massive bleeding and TBI. This safety profile, coupled with the fact that it does not require refrigerated storage, makes it attractive in the austere setting as well.

Civilian and Military Uses: Injuries are the leading cause of death for individuals 46 years and younger in the United States, with TBI affecting nearly 1.7 million people each year. Bleeding and TBI are the leading causes of death in combat trauma, with massive bleeding being the #1 cause of preventable deaths.