Optimizing a Gauze Dressing That Effectively Delivers Tranexamic Acid, Thrombin, and Calcium for Severe Hemorrhage in Multidomain Operations

Bleeding is a major cause of death for both civilians and military personnel. During Operation Iraqi Freedom and Operation Enduring Freedom between 2001-2011, 976 injury mortalities on the field were deemed potentially survivable, with 90.9% associated with hemorrhage. Bleeding is especially difficult to treat at anatomical junctions (aka 'junctional hemorrhage'), such as the groin or armpit, and during combat scenarios when Soldiers are under continued assault. Typical strategies for stopping bleeding, such as compressing the wound, are less feasible in these situations. Management of bleeding can be further complicated when a patient's blood clotting system becomes dysfunctional, a condition known as trauma-induced coagulopathy (TIC). There are drugs for reducing bleeding and re-bleeding during TIC, such as tranexamic acid (TXA) and thrombin, but their use is mainly restricted to the hospital. The proposed work aims to move these drugs far-forward into the Soldiers' hands where they are needed most, by developing a new wound dressing carrying these drugs to treat these severe and complicated bleeding scenarios. When applied, the new dressing, named 'CounterFlow-Gauze,' bubbles to propel TXA and thrombin throughout the wound site. We have shown that this enhances the effectiveness of these drugs in halting severe bleeding and allows them to stop junctional hemorrhage better than current standards when tested in animals, particularly when the wound cannot be compressed. We expect that it will be effective in Soldiers with non-compressible bleeding with TIC, a scenario currently associated with many combat deaths.

We will complete the following steps to move CounterFlow-Gauze toward adoption by the US Army:

(1) Optimize the formulation of CounterFlow. To ensure CounterFlow's efficacy and short-term safety while decreasing its cost, we will determine the minimum dose of thrombin required to halt junctional hemorrhage.

(2) Demonstrate CounterFlow's efficacy and ease-of-use. Using a swine model of severe hemorrhage, we will compare the efficacy to the current standard-of-care and receive input from end-users such as combat medics and experts in battlefield medicine.

(3) Determine storage conditions and quality assurance for CounterFlow. CounterFlow is expected to have a long shelf-life under storage conditions typical of battlefield scenarios, which must be demonstrated rigorously to ensure consistent quality in combat settings.

(4) Generate a manufacturing process by combining the results of previous work and the proposed work to incorporate CounterFlow into the US military supply chains. The CounterFlow formulation is simple and closely resembles existing gauze packing used by the US military; we will verify this and manufacture it to the appropriate standards.

CounterFlow is clinically applicable to all combat personnel at risk of injury and bleeding. Reports estimate that 19% of combat deaths in Afghanistan in 2006 could have been prevented by effective management of bleeding, which CounterFlow is specifically designed to address. In Iraq, a dressing that could treat even the most difficult bleeds, such as those complicated by TIC, could have saved the lives of hundreds of U.S. Soldiers. Additionally, all cases of bleeding involve risks of anemia, disability, and requirements for blood transfusions, and this can be partially mitigated by more effective hemorrhage control. CounterFlow is a reformulation of current, clinically used drugs for bleeding, is easy to use, and can be administered on the frontlines following trauma. CounterFlow addresses the priorities of Combat Casualty Care Research Program Focus Areas 1 and 2 because it will help to immediately stabilize casualties on the battlefield and during transport, and improve survival when evacuation is delayed.

We aim to begin field-testing CounterFlow in 2021. To accomplish this, our preliminary results and the results obtained by the proposed work will be used to engage with the US Food and Drug Administration and determine the experiments required to begin using CounterFlow during combat. Since CounterFlow is designed to treat severe traumatic bleeding, its first clinical trial will be treating injured Soldiers, leading to an immediate benefit for Soldiers. CounterFlow will reduce death and disability in Service members and subsequently improve the quality of life for Veterans and their families.