Portable normothermic ex-vivo lung perfusion, ventilation, and functional assessment with the Organ Care System on donor lung use for transplantation from extended-criteria donors (EXPAND): a single-arm, pivotal trial
Portable normothermic ex-vivo lung perfusion, ventilation, and functional assessment with the Organ Care System on donor lung use for transplantation from extended-criteria donors (EXPAND): a single-arm, pivotal trial
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DOI：
10.1016/s2213-2600(19)30200-0
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发表时间：
2019-11-01
影响因子：
76.2
通讯作者：
Van Raemdonck, Dirk
中科院分区：
文献类型：
--
作者：
Loor, Gabriel;Warnecke, Gregor;Van Raemdonck, Dirk
背景：由于多种复杂和多因素的原因，供肺移植在实体器官移植中的使用率最低;其中一个可能发挥重要作用的领域是冷缺血储存的能力有限。EXPAND试验的目的是评估常温便携式器官护理系统（OCS）肺灌注和通气对来自扩展标准供体和循环死亡后供体的供体肺使用的有效性，这些供体很少使用。如果符合以下一项或多项标准，则纳入来自扩展标准供体的肺：供体肺中动脉氧分压（PaO 2）与吸入氧气的空气分数浓度（FiO（2））之比为300 mm Hg或更小;预期缺血时间超过6小时;供体年龄≥ 55岁;或来自循环死亡后供体的肺，招募并使用OCS Lung进行评估。如果肺显示OCS肺变量稳定，PaO 2：FiO（2）大于300 mm Hg，则进行肺移植，并被移植外科医生接受。患者为成人双侧肺移植受者。主要疗效终点是移植后30天患者生存率和移植后72小时内无国际心肺移植学会原发性移植物功能障碍3级（PGD 3）的复合终点，预先设定的客观性能目标为65%。主要分析人群为所有移植受者。结果2014年1月23日至2016年10月23日期间，对93个肺对进行了灌注、通气和OCS肺评估。ClinicalTrials.gov 12个肺不符合OCS移植标准，因此81个肺适合移植。由于后勤原因，两个肺被排除在外，因此79个（87%）符合条件的肺被移植。79例患者中有43例（54%）达到了主要终点，但未达到客观性能目标。79例患者中35例（44%）在最初72 h内有PGD 3。79例患者中有78例（99%）在移植后30天存活。肺移植相关的严重不良事件（呼吸衰竭和主要肺部相关感染）的平均数量为每例患者0.3起事件（SD 0.5）。解释尽管缺少客观的主要终点，便携式OCS肺导致87%的供体肺用于移植，具有优异的临床结果。许多被其他移植中心拒绝的肺都使用这种新技术成功移植，这意味着它的使用有可能增加全球肺移植的数量。如果将这些肺保存在冰上，是否可以获得类似的结果尚不清楚，这仍然是未来研究的一个领域。版权所有（C）2019 Elsevier Ltd.保留所有权利。
Background Donor lung use for transplantation is the lowest among solid organ tranplants because of several complex and multifactorial reasons; one area that could have a substantial role is the limited capabilities of cold ischaemic storage. The aim of the EXPAND trial was to evaluate the efficacy of normothermic portable Organ Care System (OCS) Lung perfusion and ventilation on donor lung use from extended-criteria donors and donors after circulatory death, which are rarely used.Methods In this single-arm, pivotal trial done in eight institutions across the USA, Germany, and Belgium, lungs from extended-criteria donors were included if fulfilling one or more of the following criteria: a ratio of partial pressure of arterial oxygen (PaO2) to fractional concentration of oxygen inspired air (FiO(2)) in the donor lung of 300 mm Hg or less; expected ischaemic time longer than 6 h; donor age 55 years or older; or lungs from donors after circulatory death that were recruited and assessed using OCS Lung. Lungs were transplanted if they showed stability of OCS Lung variables, PaO2:FiO(2) was more than 300 mm Hg, and they were accepted by the transplanting surgeon. Patients were adult bilateral lung transplant recipients. The primary efficacy endpoint was a composite of patient survival at day 30 post-transplant and absence of The International Society for Heart & Lung Tranplantation primary-graft dysfunction grade 3 (PGD3) within 72 h post-transplantation, with a prespecified objective performance goal of 65%. The primary analysis population was all transplanted recipients. This trial is registered with ClinicalTrials.gov, number NCT01963780, and is now complete.Findings Between Jan 23, 2014, and Oct 23, 2016, 93 lung pairs were perfused, ventilated, and assessed on the OCS Lung. 12 lungs did not meet OCS transplantation criteria so 81 lungs were suitable for transplantation. Two lungs were excluded for logistical reasons, hence 79 (87%) of eligible lungs were transplanted. The primary endpoint was achieved in 43 (54%) of 79 patients and did not meet the objective performance goal. 35 (44%) of 79 patients had PGD3 within the initial 72 h. 78 (99%) of 79 patients had survived at 30 days post-transplant. The mean number of lung graft-related serious adverse events (respiratory failure and major pulmonary-related infection) was 0.3 events per patient (SD 0.5).Interpretation Despite missing the objective primary endpoint, the portable OCS Lung resulted in 87% donor lung use for transplantation with excellent clinical outcomes. Many lungs declined by other transplant centres were successfully transplanted using this new technology, which implies its use has the potential to increase the number of lung transplants performed worldwide. Whether similar outcomes could be obtained if these lungs were preserved on ice is unknown and remains an area for future research. Copyright (C) 2019 Elsevier Ltd. All rights reserved.