GanD, Inc. — Department of Defense SBIR Phase II: DHA172-009

Description

Severe hemorrhage causes more than 60,000 deaths per year in the US, and 1.9 million deaths per year globally. In military settings, hemorrhage is the leading causing of death following trauma and accounts for >90% of potentially preventable, combat-related deaths prior to the casualty reaching a medical treatment facility and 80% of deaths in the hospital phase of casualty care. Civilian and military guidelines recommend the use of whole blood and blood components for resuscitation following severe hemorrhage, but the availability of blood and blood components in prehospital and tactical settings is limited to non-existent. Consequently, the fluids that are most often available for resuscitation in pre-hospital and/or tactical settings are simple crystalloid solutions (e.g. normal saline or Lactated Ringer’s solution) and, in some cases, a semisynthetic colloid solution (e.g. Hextend). These resuscitation fluids transiently expand blood volume and increase blood pressure, but they can also induce or exacerbate well-known and significant detrimental effects including acidosis, coagulopathies, acute kidney injury and edema. The objective of the proposed work is the further development of the GND resuscitation fluid which we have shown improves cardiovascular function and outcomes following severe hemorrhage. In our previous Phase I and Phase II studies, we demonstrated in animal models of severe hemorrhagic shock, that the GND resuscitation fluid improves physiologic markers such as pH, lactate, and base deficit, returned heart rate and blood pressure to normal levels, and improved overall outcomes. The current proposal is to extend these initial studies and develop data for use in the FDA regulatory process to advance the technology into the clinic. We propose to conduct: 1) a dose ranging study to establish a safe dose for use in Good Laboratory Practice (GLP) safety and toxicity studies; 2) a GLP acute toxicity study in rodents; 3) in-vivo mechanistic studies to understand the leakage of i.v. fluids from the blood vessels; and, 4) in-vitro studies to understand the mechanism of GND action. We anticipate that our innovative resuscitation fluid will provide significant improvements in patient outcomes following traumatic hemorrhage and will evolve to become the new standard-of-care.