Clinical Development of Non-compressible Hemostatic Agent for High-Volume Hemorrhage

Biomedica Management Corporation, New York NY

Investigators

Abstract

DESCRIPTION (provided by applicant): ClotFoam(R), is a novel adhesive sealant composition and second-generation hemostatic agent. This biological agent was designed to arrest moderate to severe blood loss arising from intracavitary traumatic injury or intraoperative hemorrhage without compression, stitches or staples. Control of Intraoperative hemorrhage in laparoscopic surgery-which is increasingly becoming a suitable alternative to open surgery-can be extremely difficult, and often results in conversion to open laparotomy. Intraoperative hemorrhage during liver resection and other laparoscopic procedures remain a major risk which affects both immediate and long-term results. There is no available non-compressible product to control hemorrhage in cases of high-volume intraoperative bleeding in laparoscopic procedures. Therefore, a non- compressible hemostatic control in laparoscopic surgery will result in reduction of blood loss, postoperative pain, hospital stay and complications following these procedures. Also, there are no available hemostatic products for use in trauma outside the operating room. 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 United States is due to road traffic 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 fatal. With early and effective hemorrhage control, more lives can be saved than by any other measure. Proof of concept studies supported by the National Heart Lung and Blood Institute and by the Department of Defense (DARPA and the U.S. Army) in the swine model, have established the remarkable sealing properties of the agent. ClotFoam employs a new technology that bypasses the traditional mixture in situ of thrombin and fibrinogen, which translates in greater clotting efficacy and safety. The agent's competitive advantages over available technologies include a wide range of applications and uniqueness for use in cases of high-volume bleeding, and its rapid effect. ClotFoam(R) is also a plasmin-depleted aprotinin-and-thrombin-free fibrin sealant presenting no risk of autoimmune reaction to blood products. ClotFoam's fibrin components can be stored in a refrigerator at 40C ready-to-use. There is no need to unfreeze, mix or dissolve the components. Unlike other fibrin sealants, it does not present a risk of thrombin self-cleavage and fibrinogen proteolytic degradation, which can severely reduce the efficacy of the agent over time. Its production costs are much lower than available fibrin sealants. GLP preclinical studies by the National Heart Lung and Blood Institute have compared the hemostastic effect of ClotFoam against GelFoam (Pfizer), without compression or sutures in three surgical protocols producing moderated to severe venous and arterial bleeding. The study has established the efficacy and safety of the agent, and produced the necessary data to submit an Investigational New Drug Application (IND) to the Food and Drug Administration, toward the conduction of clinical trials. The goal of this project is to conduct clinical trials with the non-compressible hemostatic agent ClotFoam(R) as required by the Food and Drug Administration (FDA), for advancing the development of the sealant toward Biologic License as a general hemostatic. The research strategy to obtain approval for ClotFoam(R) as a general non-compressible hemostatic agent is to establish efficacy and safety in three distinct protocols that cover different body organs and tissues as well as applications. These protocols include: laparoscopic partial nephrectomy, laparoscopic liver resection and post-traumatic (hemodynamically stable and non-coagulopathic), spleen laceration. Significance: The proposed technology will significantly improve the treatment of civilian and military trauma injuries related to peritoneal hemorrhage, allow safe evacuation of the injured to definitive-care centers, and reduce casualties of combat. It will allow for expanding the use of minimally-invasive surgical procedures and provide a method to stop bleeding in laparoscopic surgery. ClotFoam(R) could have an important impact in emergency medicine, trauma and surgery, as well as a substantial share of the $ 1,7 billion a year U.S. projected market for second-generation surgical sealants. The core fibrin component technology developed by our company could be used by other surgical sealant and wound healing products manufacturers, considerably expanding the option for the treatment of blood loss and wound healing. Substantial economic activity will be generated from the global provision of this core component.