Extended Cardiac Preservation

描述（由申请人提供）：该项目的长期目标是将一种产品商业化，使移植前的人类心脏保存得到实质性改善。将人类临床心脏保存时间显著延长至24小时或更长时间的能力，将允许跨洲前瞻性匹配，并有望为潜在的数千名移植受者带来临床结果。第一阶段的研究为自动间歇灌注装置的可行性提供了概念验证，该装置与第一阶段描述的保存溶液（URS）一起使用，成功地将犬心脏保存了至少24小时。I期数据还表明，与目前的商业保存配方相比，单独使用URS，而不是与间歇灌注联合使用，可大大延长心脏保存时间。基于这些发现，现在我们的策略是依次推出两种产品：首先，URS作为心脏保存的独立产品，然后，间歇性灌注装置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，我们计划以动物模型移植后存活为终点，证明URS在24小时储存中的效用，并研究URS在保存人类心脏方面的局限性。我们打算利用这些数据作为证据，说服FDA批准21世纪医学进行多中心、随机的人体临床试验，开始ii期临床试验。此外，在II期，间歇性灌注装置作为一种强大的保存方式将继续发展。最终，该设备可能会成为目前设想的第二代产品。然而，人类心脏II期研究的数据也可能表明，URS间歇灌注对于延长人类心脏保存确实是必要的。如果是这种情况，联合产品，URS与间歇灌注系统，将得到更优先的测试。

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.