SBIR-STTR Award

The published data has demonstrated that the currently available resuscitation fluids have detrimental effects on trauma outcomes.By addressing these deficiencies it is expected that the outcomes will improve. The crystalloid based resuscitation fluid in development by GanD Inc. has been designed to address all of the shortcomings of the currently available solutions.The solution, GND-001, is a crystalloid with a decreased chloride concentration to reduce hyperchloremic acidosis and buffered with acetate, which can be utilized as a Kreb cycle intermediate.The overall concept is to replace metabolic components consumed in response to trauma and hemorrhage.These components including amino acids, Kreb cycle intermediates, and micronutrients have been identified using metabolomic profiling of trauma patients.We have also include specific vitamins as the literature has shown that certain vitamins have potent anti-inflammatory effects, such as Vitamin E derivatives that have been investigated in acute radiation sickness.Additionally, the GND-001 will be calcium free to allow the co-administration of blood products with the fluid. We believe that GND-001 will improve outcomes following severe hemorrhage by replacing lost components and aid in the recovery at the cellular level.

Problem: Currently available resuscitation fluids have been shown to induce detrimental effects on trauma outcomes.Objective: The objective of this proposal is to use the data from the successful Phase 1 studies to guide the continued development and testing of the novel resuscitation fluid (GND-001), which has been designed to address the deficiencies of current resuscitation fluids.Proposed work and expected results:The proposed work will involve refining the GND 001 formulation based on data from the Phase I proof-of-concept studies and in vitro testing using an endothelial cell model.The refinements to GND-001 will be tested for efficacy in a small animal hemorrhagic shock model compared to a) the original prototype as a benchmark, and b) the standard-of-care control.We will also examine the effects of the resuscitation fluid in a large animal hemorrhagic shock model.The swine model is well defined and the size of the animal allows for a longer study period, additional studies such as coagulation assays, and more frequent assay intervals that are not possible in the rodent model due to volume restrictions.Based on the phase I results, we expect the results to show improvements in acidosis and base deficit, and improvements in outcome. ---------- 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.