Clinical Development of Hemostatic Agent ClotFoam for Severe Hemorrhage

严重出血止血剂ClotFoam的临床开发

• 批准号: 8441486
• 负责人: GRANT BOCHICCHIO
• 金额: $ 101.26万
• 依托单位: BIOMEDICA MANAGEMENT CORPORATION
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-28 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8441486
• 关键词: Abdomen; Absorbable Gelatin Sponge; Accidents; Address; Adhesives; Advanced Development; Affect; Aprotinin; Autoimmune Process; Award; Biodegradation; Biological; Biological Products; Bypass; Caring; Cause of Death; Cessation of life; Clinical; Clinical Trials; Coagulation Process; Complication; Conduct Clinical Trials; Data; Department of Defense; Development; Economics; Effectiveness; Emergency Medicine; Emergency Situation; Ensure; Evaluation Research; Event; Excision; Family suidae; Fibrin; Fibrin Tissue Adhesive; Fibrinogen; Generations; Goals; Grant; Hemoperitoneum; Hemorrhage; Hemostatic Agents; Hemostatic function; Hospitals; In Situ; Income; Injury; Investigational New Drug Application; Laceration; Laparoscopic Surgical Procedures; Laparotomy; Length of Stay; Licensing; Liver; Liver parenchyma; Manufacturer Name; Marketing; Maryland; Measures; Medical; Methods; Military Personnel; Minimally Invasive Surgical Procedures; Minor; Modeling; National Heart, Lung, and Blood Institute; Nephrectomy; Operating Rooms; Operative Surgical Procedures; Organ; Patients; Phase; Physiological; Plasmin; Postoperative Pain; Procedures; Production; Property; Protocols documentation; Publishing; Reaction; Recovery; Recovery of Function; Research; Risk; Safety; Site; Small Business Innovation Research Grant; Solid; Spleen; Stress; Surgical sutures; Technology; Testing; Thrombin; Time; Tissue Adhesives; Tissues; Traffic accidents; Translating; Trauma; United States; United States Food and Drug Administration; Venous; Wound Healing; base; biomaterial compatibility; blood product; combat; commercialization; cost; design; improved; injured; new technology; novel; preclinical study; quantum; response; seal; secondary outcome; success; technology development; wound

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.

描述(由申请人提供)：“ClotFoam(R)”是一种新型粘合密封剂组合物和第二代止血剂。这种生物制剂旨在止住因腔内创伤性损伤或术中出血而产生的中到重度失血，而不需要压迫、缝合或缝合。腹腔镜术中出血的控制可能非常困难，通常会导致改用开腹手术。肝切除和其他腹腔镜手术中出血仍然是影响近期和长期效果的主要风险。在腹腔镜手术中大量出血的情况下，没有可用的不可压缩产品来控制出血。因此，在腹腔镜手术中采用不可压缩止血控制将减少失血量、术后疼痛、住院时间和术后并发症。此外，在手术室外也没有可用于创伤的止血产品。创伤引起的出血是事故死亡的主要原因，也是战场上死亡的主要原因。美国医院收治的创伤病例中，超过40%是由于道路交通事故造成的。在常规战争中，出血是战场上死亡的主要原因。这些死亡中的绝大多数发生在伤者可以被转移到治疗设施之前。已经开发了组织粘合剂和密封剂来控制出血；但是，由于所有现有的腹腔室内出血止血剂都是设计在手术室使用的，而不是在事故现场或战场的紧急情况下使用，因此出血往往是致命的。早期有效地控制出血，比任何其他措施都可以挽救更多的生命。在猪模型中，由国家心肺和血液研究所和国防部(DARPA和美国陆军)支持的概念验证研究已经确定了该试剂的显著密封性能。ClotFoam采用了一种新技术，绕过了传统的凝血酶和纤维蛋白原原位混合物，这转化为更高的凝血效率和安全性。与现有技术相比，该制剂的竞争优势包括广泛的应用范围和在大出血情况下使用的独特性，以及其快速起效。ClotFoam(R)也是一种纤溶酶耗竭、无抑肽酶和无凝血酶的纤维蛋白密封剂，不存在对血液产品发生自身免疫反应的风险。ClotFoam的纤维蛋白成分可以储存在40摄氏度的冰箱中，即可使用。不需要解冻、混合或溶解这些成分。与其他纤维蛋白密封剂不同，它不存在凝血酶自我裂解和纤维蛋白原蛋白降解的风险，这可能会随着时间的推移而严重降低该试剂的疗效。它的生产成本远远低于现有的纤维蛋白密封剂。国家心、肺和血液研究所的GLP临床前研究比较了ClotFoam和GelFoam(辉瑞)的止血效果，在三种手术方案中，ClotFoam没有压迫或缝合，产生中度到严重的静脉和动脉出血。这项研究已经确定了该制剂的有效性和安全性，并提供了必要的数据，以向食品和药物管理局提交新药调查申请(IND)，以进行临床试验。该项目的目标是按照美国食品和药物管理局(FDA)的要求，使用不可压缩止血剂ClotFoam(R)进行临床试验，以推动这种密封剂向生物许可方向发展，成为一种普通止血药物。获得批准将ClotFoam(R)作为一种通用的非压缩止血剂的研究战略是在三种不同的方案中确定有效性和安全性，这三种方案涵盖不同的身体器官和组织以及应用。这些方案包括：腹腔镜肾部分切除术、腹腔镜肝切除术和创伤后(血流动力学稳定和非凝固性)、脾撕裂。意义：拟议的技术将显著改善与腹膜出血相关的平民和军事创伤伤害的治疗，允许将伤者安全疏散到最终护理中心，并减少战斗中的伤亡。它将允许扩大微创手术程序的使用，并提供一种在腹腔镜手术中止血的方法。ClotFoam(R)可能在急诊医学、创伤和外科手术领域产生重要影响，并在美国预计每年17亿美元的第二代外科密封剂市场中占有相当大的份额。我们公司开发的核心纤维蛋白成分技术可以被其他外科密封剂和伤口愈合产品制造商使用，极大地扩大了出血和伤口愈合的治疗选择。这一核心组成部分的全球供应将产生大量经济活动。