Clinical Development of Hemostatic Agent ClotFoam for Severe Hemorrhage
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135 WEST 41ST STREET SUITE 608, NEW YORK, NY, -
AbstractDESCRIPTION (provided by applicant): Hemorrhage resulting from traumatic injuries is a major cause of death in accidents, and the primary cause of death on the battlefield. Over 40% of the trauma cases admitted at hospitals in the USA, are due to road traf fic accidents. Hemorrhage is the primary cause of death on the battlefield in conventional warfare. The vast majority of these deaths occur before the injured can be transported to a treatment facility. Tissue adhesives and sealants have been developed to control bleeding; but, since all existing haemostatic agents for abdominal intracavitary bleeding are designed to be used in the operating room, not in an emergency at the site of accident or in the battlefield, hemorrhage is often lethal. With early and e ffective hemorrhage control, more lives can be saved than by any other measure. The goal of the project, is to determine the effectiveness and safety of ClotFoam, a novel gelatin- based fibrin sealant, as a hemostatic agent to stop hemorrhage without compr ession in cases of severe hemorrhage resulting from intracavitary wound grade III/IV (as measured in the liver), and a novel method of application to be used outside the operating room. The use of this technology can be extended for use in cases of minimal ly invasive surgery, laparoscopy, brain and gynecological surgery. This technology is based on the physical and coagulation properties of a fibrin sealant embedded in a scaffold, enhanced by pro-coagulants, and delivered as a foam through a C02-propelled d elivery device. Phase I studies have provided the proof of concept for the use of ClotFoam as non-compressible technology in cases of hemorrhage resulting from very severe trauma (grade 3/grade 4) and in laparoscopic or minimally invasive surgical proced ures, by establishing the ability of the agent to adhere to lacerated tissue in a pool of blood. Data obtained from studies in rats, rabbits, and pigs have demonstrated that ClotFoam can generate an adaptable foam that is distributed uniformly; and adheres to the abdominal cavity, even under profuse bleeding, when it is injected intraperitoneally, improving the adhesiveness between lacerated tissue, and initiating a rapid clot formation. Furthermore, Clotfoam's fibrin sealant component has been developed wi th an advanced technology that overcomes two fundamental problems encountered by fibrin sealants: Shelf life and autoimmune reaction against thrombin. The specific aims of this phase II proposal are to 1) develop a method to sterilize and preserve the agen t under ambient conditions, and determine the proteolitic degradation, activity and shelf life of fibrin components maintained under standard refrigeration conditions; 2) Evaluate the material biocompatibility in a subdermal model in the rat. Once it has b een determined that the formulation can be sterilized and it is biocompatible, and therefore will not require further modifications, we will 3) develop a standardized animal model (pig) to study the effects of hemostatic agents in cases of non-compressible severe hemorrhage, subsequent to grades III and IV wounds to the liver, resulting from severe traumatic injury; 4) evaluate the ability of ClotFoam to achieve hemostasis in a pig model, following progressively severe hemorrhage secondary to high-flow blee ding caused by grade III, IV liver injury; and assess animal survival at 1 hour, as compared to the control. And finally 5) we will assess safety of the agent through the evaluation of immunological risks, as well as prevention of adhesions, abdominal comp artment syndrome, and delayed hematoma and/or edema formation. This data will be used to file for an Investigational New Drug (IND) application and proceed to the clinical stage. PUBLIC HEALTH RELEVANCE: In an age of speed, civil violence and armed conflic ts, the incidence of penetrating and blunt injuries to the abdomen has been on the increase. On average, 41.8% of the trauma cases admitted at hospitals, nationwide, are due to road traffic accidents. Also, hemorrhage remains the primary cause of death on the battlefield in conventional warfare. Morbidity and mortality from these abdominal injuries pose a formidable problem, especially in young adults. Early and effective hemorrhage control could theoretically save more lives than any other measure. Unfortu nately, all existing haemostatic agents for abdominal intracavitary bleeding day available today are designed to be used in the OPERATING ROOM-not at the locus of injury (i.e. battlefield, car accident, or scene of a shot wound). All available hemostatic a gents and sealants require compression, and therefore they cannot be used even in cases of minimally invasive surgery such as laparoscopic surgery. ClotFoam, a novel agent that allows to inject a sealing foam inside a body cavity to seal wounds and stop bl eeding has proved to be effective in animal studies. The agent is applied through a mixing needle, similar to a Veress needle-releasing a foam inducer and procoagulants incorporated into gelatin sealants that adhere to injured tissue, compress the wound an d stops the bleeding. In this study we to further study the effectiveness and safety, including biocompatibility of ClotFoam in cases of severe hemorrhage caused by grade III and IV traumatic wounds which-if not treated immediately-would lead to exsanguina tions. This therapeutic approach will reduce killed in action (KIA) rate, provide new therapeutic tools for paramedics, increase life-saving capability for the medic, offer new t options for laparoscopic and other minimally invasive surgery, and reduce nee d for surgery and transfusion.
* information listed above is at the time of submission.