More and Better Lungs: Ex-Vivo Perfusion of Lungs from Non-Heart-Beating Donors

更多更好的肺：来自无心跳供体的肺的离体灌注

• 批准号: 8427986
• 负责人: Thomas M. Egan
• 金额: $ 87.22万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8427986
• 关键词: Accident and Emergency department; Address; Americas; Ancillary Study; Animal Model; Area; Biological Assay; Biological Markers; Blood Circulation; Blood donor; Blood flow; Brain Death; Brain Injuries; Categories; Cause of Death; Cessation of life; Clinical Trials; County; Emergency medical service; Functional disorder; Future; Goals; Government Agencies; Health; Healthcare Systems; Heart; Hour; Human; Human Resources; Incubated; Individual; Institutional Review Boards; Law Enforcement; Leadership; Liquid substance; Lung; Lung Transplantation; Lung diseases; Medical Examiners; Methods; Metric; Natural Immunity; North Carolina; Organ; Organ Donor; Organ Procurements; Organ Retrievals; Organ Transplantation; Outcome; Patient Care; Patients; Perfusion; Phase II Clinical Trials; Policies; Population; Procedures; Protocols documentation; Quality of life; Reaction Time; Reperfusion Injury; Retrieval; Safety; Sample Size; Scanning; Serological; Services; Source; Staging; State Government; Structure of parenchyma of lung; Sudden Death; Technology; Testing; Time; Transplantation; Transportation; United States; Up-Regulation; Ventilator; X-Ray Computed Tomography; compare effectiveness; ex vivo perfusion; improved; injured; metabolomics; mortality; phase 2 study; phase 3 study; success

DESCRIPTION (provided by applicant): Lung disease is the third leading cause of death in the United States. Lung transplant could improve quality of life and enhance survival in many lung disease patients. However, lung transplantation is severely limited by an inadequate number of suitable lungs for transplant from conventional organ donors - individuals who sustain a lethal brain injury, but who are incubated and ventilated before brain death occurs. Because most lungs from conventional organ donors are not suitable for transplant, only 1,700 lung transplants are performed annually in the U.S. However, lung tissue remains viable after circulatory arrest. In animal models, the PI of this project showed that lungs can function well after transplant, even if retrieved hours after death. Each year, more than 750,000 people in the U.S. are victims of sudden death; if lungs could be retrieved for transplant from some of these people - non-heart-beating donors (NHBDs) - the lung donor shortage could be eliminated. The PI has performed ex-vivo lung perfusion (EVLP) to determine suitability of human lungs initially turned down for transplant from conventional organ donors. Safety of transplanting these lungs after EVLP has recently been demonstrated. This proposed Phase 2 clinical trial will demonstrate safety and efficacy of transplant of lungs retrieved from NHBDs after death, assessed by EVLP, We will accomplish this Specific Aim: To demonstrate non-inferiority of lung transplant using lungs retrieved from NHBDs assessed by EVLP compared to lung transplant from conventional brain dead organ donors. We will obtain lungs from Maastricht Category 1 and 2 NHBDs in a large-population North Carolina county (Wake) and from targeted emergency rooms. We will apply established methods of EVLP and ex-vivo CT scan to evaluate suitability for transplant. Acceptable lungs will be transplanted at UNC and Duke under IRB-approved protocols. Outcomes will be compared to patients contemporaneously transplanted with lungs from conventional organ donors. Because lungs from NHBDs have not been injured by a prolonged interval of brain death, lungs retrieved from NHBDs may not only be much more plentiful; they may be superior to lungs currently being transplanted from conventional brain-dead donors. Timely retrieval of lungs from NHBDs requires coordination of EMS, law enforcement, medical examiners, and OPO personnel. Through the Office of the N.C. Secretary of Health and Human Services, we commenced a dialogue with leadership of state agencies to facilitate timely lung retrieval from NHBDs. We will use experts at Lung Banks of America, a not-for-profit corporation, to analyze time flow metrics from declaration of death to lung retrieval. With N.C. state government agencies, we will develop practices and policies to improve the yield of successful lung retrieval from NHBDs that can be implemented in N.C. and across the U.S. An ancillary project will determine metabolomic biomarkers for suitability of NHBD lungs for EVLP assessment, and biomarkers associated with poor function after lung transplant. Successful study completion will revolutionize lung transplant and the care of patients with end-stage lung disease.

描述（由申请人提供）：肺部疾病是美国第三大死因。肺移植可以改善许多肺病患者的生活质量并提高生存率。然而，肺移植受到传统器官捐献者（遭受致命性脑损伤，但在脑死亡发生前经过培养和通气）的合适肺移植数量不足的严重限制。由于大多数来自传统器官捐献者的肺不适合移植，因此美国每年仅进行 1,700 例肺移植。然而，肺组织在循环停止后仍然具有活力。在动物模型中，该项目的 PI 表明，即使在死亡数小时后取出，肺在移植后仍能发挥良好功能。美国每年有超过 75 万人猝死；如果可以从其中一些人（无心跳捐献者（NHBD））中取出肺进行移植，那么肺捐献者短缺的问题就可以得到解决。 PI 进行了离体肺灌注 (EVLP)，以确定最初拒绝接受传统器官捐赠者移植的人肺是否适合。 EVLP 后移植这些肺的安全性最近已得到证实。这项拟议的 2 期临床试验将证明由 EVLP 评估的从 NHBD 中回收的肺移植的安全性和有效性，我们将实现这一具体目标：与传统脑死亡器官捐献者的肺移植相比，证明使用由 EVLP 评估的从 NHBD 中回收的肺移植的非劣效性。我们将从北卡罗来纳州人口众多的县（韦克）的马斯特里赫特 1 类和 2 类 NHBD 以及目标急诊室获取肺部。我们将应用 EVLP 和离体 CT 扫描的既定方法来评估移植的适合性。根据IRB批准的协议，合格的肺部将在北卡罗来纳大学和杜克大学进行移植。结果将与同时移植传统器官捐献者肺部的患者进行比较。 由于 NHBD 的肺并未因长时间的脑死亡而受到损伤，因此从 NHBD 中取出的肺可能不仅数量更多，而且数量也可能更多。它们可能优于目前从传统脑死亡捐献者移植的肺。从 NHBD 及时回收肺部需要 EMS、执法部门、法医和 OPO 人员的协调。通过北卡罗来纳州卫生与公共服务部部长办公室，我们开始与州机构领导层进行对话，以促进 NHBD 及时进行肺移植。我们将聘请非营利性公司美国肺库的专家来分析从宣告死亡到肺移植的时间流指标。我们将与北卡罗来纳州政府机构一起制定实践和政策，以提高从 NHBD 成功取肺的产量，这些做法和政策可以在北卡罗来纳州和整个美国实施。一个辅助项目将确定 NHBD 肺部是否适合 EVLP 评估的代谢组生物标志物，以及与肺移植后功能不良相关的生物标志物。研究的成功完成将彻底改变肺移植和终末期肺病患者的护理。