First-in-Human Use of an Artificial Lung for Ambulatory Respiratory Support

描述(由申请人提供)：急性和慢性终末期肺部疾病(ESLD)正在增加医疗保健问题。目前，当机械通气失败时，只有体外膜氧合(ECMO)系统可用，其组件经过设计并合格，可持续几个小时。这些通常与严重的并发症有关，一般仅限于床边使用。就像为应对顽固性心力衰竭而进一步发展的机械循环支持领域一样，可穿戴、生物兼容的一体化泵-肺将为患者提供比现有选择更大的优势。这样的设备可能会为急性损伤后的自然肺愈合提供一个延长的可移动平台，为移植或目的地治疗，或为新的肺再生治疗提供桥梁。在NHLBI的支持下，我们在开发用于非卧床呼吸支持的新型人工泵-肺(APL)装置方面取得了显著进展。这项技术几乎可以转化到临床上供人类使用。这项转化研究的目标是完成先进的原型泵肺(APL)的开发，用于门诊(FIM)的第一次人体试验。APL将与套管和由电子设备、电池和氧气源组成的便携式驱动器连接，作为人工肺泵系统(APLS)。APLS将根据FDA的指南进行临床前验证和测试，以获得研究设备豁免(IDE)。该提案的四个具体目标是：(1)完成包括APL、套管、诊断传感器和便携式驱动器在内的临床前APLS的开发，并开发使能技术；(2)开发制造临床级APLS的工艺和工具；(3)在FDA批准的首个人体试验中使APLS有资格用于临床；以及(4)进行APLS的首次人体试验，以衡量治疗效果、基本安全性和人类反应因素。这些特定目标的成功完成将导致Keystone呼吸支持系统的出现，就像20年前推出的心力衰竭的脑室辅助装置(VAD)一样，将成为那些患有病态、急性和慢性肺部疾病的人的一种新的治疗选择。患者的生活质量将随着门诊和院外使用的APLS而显著提高

DESCRIPTION (provided by applicant): Acute and chronic end stage lung disease (ESLD) are increasing healthcare problems. Currently, when mechanical ventilation fails only extracorporeal membrane oxygenation (ECMO) systems with components designed and qualified for a few hours are available. These are often associated with serious complications and generally are restricted to bedside use. Like the further evolved field of mechanical circulatory support in response to refractory heart failure, a wearable, biocompatible integrated pump-lung would offer significant advantages to patients over existing options. Such a device might would pose a prolonged ambulatory platform for natural lung healing from acute injury, a bridge to transplant or destination therapy, or for novel lung regenerative therapies. With support from the NHLBI, we have made remarkable progress in development of a novel artificial pump-lung (APL) device for ambulatory respiratory support. The technology is near ready to be translated to the clinics for human use The goal of this translational research is to complete development of the advanced prototypical pump lung (APL) for ambulatory use in a first-in-human (FIM) trial. The APL will be joined with cannulae and a portable driver consisting of electronics, battery and oxygen source as an artificial pump lung system (APLS). The APLS will undergo preclinical validation and testing per FDA guidelines to receive an Investigational Device Exemption (IDE). Four specific aims of the proposal are: (1) to complete development of the preclinical APLS, including the APL, cannulae, diagnostic sensors and a portable driver, and develop enabling technologies; (2) to develop processes and tools for manufacturing clinical grade APLS; (3) to qualify the APLS for clinical use in an FDA approved first-in-human study; and (4) to conduct a First-in-Human trial of the APLS to measure effect of treatment, basic safety and human response factors. The successful completion of these specific aims should result in a keystone respiratory support system that will, like the introduction of ventricular assst devices (VAD) for heart failure 20 years earlier, be a new therapeutic option for those with morbid, acute, and chronic pulmonary illnesses. The quality of life for the patients will be dramatically improved with the ambulatory and "out of hospital use" APLS