Extended Cardiac Preservation

延长心脏保护

• 批准号: 6932442
• 负责人: GREGORY M FAHY
• 金额: $ 24.5万
• 依托单位: 21ST CENTURY MEDICINE, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-11-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6932442
• 关键词: Cercopithecidae; biomedical automation; cryopreservation; dogs; heart circulation; heart function; heart preservation; heart transplantation; human tissue; postoperative state; quality of life; solutions; technology /technique development

DESCRIPTION (provided by applicant): The long-term objective of this project is the commercialization of a product(s) that enables a substantial improvement in human heart preservation prior to transplantation. The ability to significantly extend human clinical cardiac preservation, to 24 hours or more, would allow transcontinental prospective matching, with expected gain in clinical outcome for potentially thousands of transplant recipients. Phase I studies provided a proof-of-concept for the feasibility of an automated intermittent perfusion device, that used in conjunction with the preservation solution (URS) described in Phase I, successfully preserved canine hearts for at least 24 hours. Data from phase I also demonstrated that the use of URS alone, not in combination with intermittent perfusion, results in substantial extension of cardiac preservation when compared to current commercial preservation formulations. Based on these findings, it is now our strategy to introduce two products sequentially: first, URS as a stand alone product for cardiac preservation, and later, an intermittent perfusion device that will build on the first product release and offer yet further extension of cardiac preservation. In phase II we plan to demonstrate the utility of URS for 24 hour storage using post-transplant survival in animal models as an end point, and to investigate the limits of URS for the preservation of human hearts. It is our intention to use this body of data as evidence to persuade the FDA to grant clearance for 21st Century Medicine to proceed with multicenter, randomized human clinical trials to begin phase Ill. Additionally, in phase II, the development of the intermittent perfusion device as a powerful preservation modality will continue. Ultimately the device may become a second generation product as currently envisioned. However, it is also possible the data from human heart studies in phase II will demonstrate that intermittent perfusion with URS is indeed necessary to achieve the desired extension of human cardiac preservation. Should that be the case, the combination product, URS with an intermittent perfusion system, will be tested with greater priority.

描述（由申请人提供）：本项目的长期目标是实现一种产品的商业化，该产品能够在移植前大幅改善人类心脏保存。将人类临床心脏保存时间显著延长至24小时或更长的能力将允许跨大陆前瞻性匹配，并预期获得潜在数千名移植受体的临床结果。I期研究为自动间歇灌注装置的可行性提供了概念验证，该装置与I期研究中描述的保存溶液（URS）结合使用，成功保存犬心脏至少24小时。来自I期的数据还表明，与目前的商业保存制剂相比，单独使用URS，而不与间歇灌注组合，导致心脏保存的实质性延长。基于这些发现，我们现在的策略是按顺序推出两种产品：首先，URS作为心脏保存的独立产品，之后，间歇灌注设备将建立在第一个产品发布的基础上，并提供心脏保存的进一步扩展。在第二阶段中，我们计划使用动物模型中的移植后存活率作为终点来证明URS用于24小时储存的实用性，并研究URS用于保存人类心脏的限制。我们打算用这些数据作为证据，说服FDA批准21世纪世纪医学进行多中心、随机人体临床试验，开始III期。此外，在第二阶段，间歇灌注装置作为一种强大的保存方式的发展将继续下去。最终，该设备可能成为目前设想的第二代产品。然而，也有可能来自II期人类心脏研究的数据将证明，使用URS进行间歇性灌注对于实现人类心脏保存的预期扩展确实是必要的。如果是这种情况，将更优先地对组合产品（带有间歇灌注系统的URS）进行试验。