OUSD (R&E) MODERNIZATION PRIORITY: General Warfighting Requirements (GWR)
TECHNOLOGY AREA(S): Bio Medical
OBJECTIVE: To reimagine the current fielded tourniquet beyond prevention of exsanguination and demonstrate next generation designs capable of delivering treatment for the prevention of infection in a prolonged care setting. The technology must retain or improve upon the original functionality and shall be in an easy-to-use format, require minimal instrumentation, lightweight, and compatible with prolonged care. The treatment delivery approach should enable deep tissue penetration of, but not limited to, antimicrobial agents post-compression towards the wound bed. The end goal for this effort is to assemble a system of systems to prevent the development of infection in an austere environment when the provision of surgical intervention is delayed over 72 hours (hrs).
DESCRIPTION: Multi-domain operations (MDO) of the future anticipate division-on-division combat operations with causality volumes and medical intervention times that mirror what was observed in WWI and WWII. In MDO, the deployment of anti-access and area denial (A2AD) technologies will not only limit evacuation to degrade the Golden Hour timeline for medical support but also constrain medical resupply, which will leave wounded Warfighters and first line medical support providers stranded in prolonged care (PC) scenarios for unknown durations. Furthermore, repeated events of mass casualty and greater dependency on PC (limited resources while being mobile) will increase the number of deaths from wounds as the infection rate will rise in wounds within 72hrs and beyond as was observed in previous conflicts. Here, the amount of wound dressings and antibiotics needed to prevent infection from polytraumatic wounds based on current US military medical doctrine designed for “Golden Hour” doctrine are untenable in PC scenarios. As a result, the need for innovative solutions that are massively scalable and distributive (i.e. affordable and for all combatants) focused on amplifying self/ buddy care (i.e. fire and forget solutions that enable less supply to be carried for longer duration or the ability of one medical provider to provide care for a high number of wounded casualties) is an urgent need. Furthermore, adding materials to the improved first aid kit (IFAK) or combat lifesaver (CLS) bag presents significant challenges. The critical need for wound infections and sepsis mitigation at point-of-care and Role 1 is to design alternative and/or adjunctive solutions that prevent infection within the first 72 hrs following injury. One approach is to reimagine components of the IFAK as a system of systems to prevent the development of infection in polytraumatic wounds by extending treatment options over 72 hrs to increase Warfighter survivability until surgical intervention. This topic explores the development of the tourniquet not only as hemorrhage control device but also as a new aspect of treatment, as a drug delivery device as well to specifically meet the need for immediate administration of infection treatment at point of injury to prevent infection in prolonged care settings.
Exsanguination (i.e. bleeding to death) and combat wound infection are the most common causes of death from survivable wounds in the history of combat. Tourniquets have been an effective means of controlling exsanguination of compressible trauma on the battlefield and in pre-hospital care to limit mortality and morbidity. Unfortunately, the evolution of tourniquets over time has been unremarkable relative to the many advances of modern medicine. According to the Tactical Combat Casualty Care (TCCC) guidelines, the initial response to penetrating battlefield trauma is to stop major hemorrhage with pressure, tourniquet, and wound packing. Wound packing includes hemostatic agents along with broad-spectrum, systemic battlefield antibiotics to prevent infection followed by casualty evacuation within the hour if the battlespace is mature. Studies have established prolonged application of tourniquets contributes to ischemic-reperfusion injury and microvascular dysfunction that accompanies altered trauma physiology such as shock and sepsis. Furthermore, prolonged tourniquet application significantly reduces systemically administered antibiotics from penetrating soft-tissue further complicating the infection resolution process. Lessons both from OIF and OEF and from civilian trauma is that “brief” application of tourniquets is generally “safe”. Current research and development on tourniquets are focused on developing smart tourniquets with pressure sensors and describing “application” duration.
Another arm of the problem is that the timing of antibiotic treatment significantly correlated with infection development process. Animal studies of open fractures revealed that early antibiotic treatment and surgical debridement within two hours prevented infection, but delays in antibiotics and surgery after two hours significantly increased the development of infections. These observations were validated in retrospective clinical studies in civilian trauma involving open fractures and further studies have revealed that administering antibiotics immediately after traumatic injury reduced infection rates significantly (i.e. 7% of infection if treated within the hour to 28% if treated after 1.5 hours). This paradigm of casualty management was successful in recent operations where medical evacuation to a higher echelon of care was possible within hours of traumatic injury. However, the conceivable lack of a reasonable timeframe for medical evacuation in large scale combat operations requires the adaption of PC to the new operational environment to meet the balanced need for ease-of-use, scalability, longevity treatment, and efficiency of treatment delivery focused on point-of-care and Role 1 care.
The ultimate goal of the technology in this request is, but not limited to, to combine exsanguination prevention and antibiotic delivery in one-step at the earliest time possible after injury. In doing so, this convergent technology should prevent infection development as decolonization measure of the wound bed (maintain agents of infection below 10^5 threshold) by rapid treatment prior to ischemic-reperfusion injury (within 1.5hrs). This is not meant to replace systemic treatment upstream of tourniquet application according to current CPG.. The intent here is also to overcome compliance issues with combat wound medication packet (CWMP) usage, extend CWMP dose for later use, and ultimately increasing survivability for surgical intervention at point-of-injury and Role 1. The aim of this SBIR is to develop a technology with commercial viability that addresses the multidimensional problems of traumatized tissue biology and to accelerate the next generation of innovations that combine, but not limited to, sensors, treatment (i.e. small molecule-based antibiotics, tissue regeneration, pain management, immune modulators, monoclonal antibodies and/or bacteriophage) delivery features and sleeve/chamber features for bio-containment. When proposing a technology, it is paramount, but not limited to, to consider the factors below:
- The starting technology must plan to have FDA or equivalent device clearance.
- The original functionality of the tourniquet cannot be compromised or traded off for a new feature.
- The original packing weight (2.7 oz) and dimensions (LxWxH- 6x2x1.5 in) should be at or near current fielded product but no more than 10% increase in weight or dimensions.
- Modular designs with a library of medications incorporating exchangeable cartridges, microneedles, micropumps, catheters, gels… etc. are welcomed, but should describe a ruggedization plan and durability of design to include mechanical systems that require minimal logistical support.
- Designs must have a manual fail-safe backup option for motorized or automated designs for active delivery.
- Treatment of choice shall cover a wide array of infectious organisms but not limited to, small molecule-based antibiotics, metal ions, lantibiotics, natural products, bacteriophages, antibodies, polymers, nano-fibers/sponges, antimicrobial peptides, and or any pathogen agnostic treatment. Stable formulations with long shelf-life (18 month +) should be considered.
- Other treatments such as analgesics for pain management, regenerative, and immune modulators are optional.
- Modular designs to include bio-containment of wounds such as severed limbs in the form of a convertible sleeve or chamber are optional.
- Built in sensors are optional.
- Ease of applications, ability to withstand water, hot and cold temperatures and minimal storage conditions will be factored in the nomination process.
- Engineering solutions overall should require minimum logistical support and should be compatible with applications in extreme environments including hot and cold temperature.
PHASE I: Given the short duration of Phase I and the high order of technology integration required, Phase I should focus on system design and development of proof-of-concept prototypes that address the treatment delivery requirement. Proposals may include different formulations of treatment. Prototypes may combine “classes” of applications into different “sets” of designs. At the end of this phase, fabricated prototypes should demonstrate feasibility, proof-of-concept and establish “release profile”, using relevant testing platforms for the proposed technology. This phase should down-select promising design as well as identify a pre-clinical animal model, such as, but not limited to, hemorrhagic shock, open fracture or soft tissue wounds with and without infection for use in Phase II. Evaluation of the product’s efficacy for controlling infection with antimicrobial activity must include data for the first 6, 24, 48, and 72 hours at a minimum, if not longer. The above time points do not represent tourniquet application on subjects but used as a bench mark and quantify duration of decolonization of wound bed and prevention of infection.
PHASE II: During this phase, the lead integrated system should be further refined from proof-of-concept into a viable product. Further optimization of the technology for deep penetration of treatments into the traumatized wound bed should be demonstrated during this phase. Qualitative and quantitative outcomes of product with regards to hemorrhage control, prevention of infection, and/or decolonization by invading organisms must be demonstrated as specific performance characteristics of the product compared to standard issued CAT. This testing should be controlled, and rigorous. Testing and evaluation of the prototype to demonstrate operational effectiveness in simulated environments shall be demonstrated. Stability of product in an austere environment should be evaluated to include extreme conditions (i.e. extreme heat, cold, wet environment). This phase should also demonstrate evidence of commercial viability of the product. Accompanying application instructions, simplified procedures, and training materials should be drafted in a multimedia format for use and integration of the product into market. Price estimate and comparison analysis for new design relative current fielded equipment and treatment shall be provided to forecast the potential cost of product. The offeror may develop a regulatory strategy for FDA clearance early to guide product development early on. Offeror may consider a pre-pre-submission communication with the FDA as an early communication for guidance.
PHASE III DUAL USE APPLICATIONS: The ultimate goal of this phase is to secure FDA clearance by developing non-DOD partnerships to demonstrate and commercialize a technology enabling the prevention of infection in wounded service members from infected traumatic combat wounds and control of hemorrhage under PC.. The global market for wilderness medicine and first responder technologies is worth over 100 billion dollars.. Appropriate partnerships to advance the technology above is encouraged at this stage to enable a commercial off-the-shelf solution for market analysis by USAMMDA WEMT or other DOD entities. Alternatively, further development, testing and evaluation of the medicated tourniquet product developed by phase II of this SBIR can be supported by CDMRP, JWMRP, and other DOD opportunities and partnerships. This effort should seamlessly be integrated into the TCCC paradigm of initial response to trauma. Once developed and demonstrated, the technology can be used both commercially in civilian or military settings to save lives. The selected contractor shall make this product available to potential military and civilian users.. If product is transitioned into Acquisition Programs of Record, the Government may work with offeror to further refine and harmonize design with other relevant products.
- Kragh JF Jr and Dubick MA. Battlefield tourniquets: lessons learned in moving cur- rent care toward best care in an army medical department at war. US Army Med Depart J 2016:29–36.
- Penn-Barwell JG, et al. Early antibiotics and debridement in- dependently reduce infection in an open fracture model. J Bone Joint Surg Br 2012;94:107–112.
- Lack WD, et al. Type III open tibia fractures: immediate antibiotic prophylaxis minimizes infection. J Orthop Trauma 2015;29: 1–6.
- Mangum LC, et al. Duration of extremity tourniquet application profoundly impacts soft-tissue antibiotic exposure in a rat model of ischemia-reperfusion injury. Injury 2019;50: 2203-2214.
- Benov A, et al. Antibiotic treatment-what can be learned from point of injury experience. Mil Med 2018;183: 466–471.
KEYWORDS: MDO, tourniquets, drug delivery, wearable, trauma, prolonged care