NOVEL Lung Trial
The NOVEL Lung Trial
The NOVEL/NOVEL Extension trial was the first prospective, multi-center clinical trial in the world designed to evaluate the safety and efficacy of Ex Vivo Lung Perfusion (EVLP) as a method to safely reassess donor lungs of unknown or questionable quality that were previously unused or rejected for transplantation.
The NOVEL Trial began in 2011 with 6 centers in the US, ultimately seeking and receiving HDE approval. The NOVEL Extension trial began in 2014, expanding to 17 centers to apply for PMA approval. All participating centers used the XPS™ with STEEN Solution™, a fully integrated and flexible system that includes all components needed to safely run normothermic EVLP.
XPS™ – First FDA approved system for EVLP
In August 2014, the FDA granted Humanitarian Device Exemption (HDE) approved use of the XPS™ with STEEN Solution™ for warm EVLP of initially unacceptable donated lungs. XPS™ with STEEN Solution™ is the first FDA approved system for EVLP of marginal lungs. In April 2019, the FDA granted Pre-Market Approval (PMA) for use of the XPS™ with STEEN Solution™ for normothermic machine perfusion of initially unacceptable excised donor lungs during which time the ex vivo function of the lungs can be reassessed for transplantation. A PMA is the most stringent FDA approval process for medical devices in the United States, with requirements for both safety and efficacy to be met.
The FDA evaluated data from the study involving 332 sets of donor lungs that were allocated into three groups: one group served as the control and were lungs initially deemed suitable for transplant that were provided to 116 recipients after standard preservation; one group were lungs initially deemed unsuitable for transplant and, after being perfused with the XVIVO Perfusion System, were implanted into 110 recipients; the third group were perfused with the XVIVO Perfusion System and were still deemed not suitable after the perfusion, and therefore were not implanted into patients. The one-year survival rate was 94 percent for the control group compared to 86.4 percent for the lung perfusion patients. The difference in rates was not deemed to be clinically significant. In addition, a post-hoc comparison to the United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients (SRTR) 12-month survival data from the same study centers as those of the NOVEL and NOVEL Extension Trial showed comparable survival (86% and 88% for the EVLP and UNOS control, respectively). An additional post-hoc analysis on the UNOS dataset was performed on the next available “control”, or the next available transplanted patient who met study inclusion/exclusion criteria. The 1-year survival for that cohort was 89% which was similar to the EVLP arm (86%).
More than 70% of lungs donated worldwide are deemed unusable and not used for transplantation. Ex Vivo Lung Perfusion (EVLP) has been developed to expand the donor pool for lung transplantation.
What is Ex Vivo Lung Perfusion (EVLP)?
Ex Vivo Lung Perfusion (EVLP) is a process of evaluating and preparing donor lungs outside of the body prior to transplantation. EVLP with the XVIVO Perfusion System (XPS™) represents the next frontier in transplant medicine.
How does it work?
EVLP with XPS™ and STEEN Solution™ is a method to assess viability of donated lungs. EVLP aims to expand the potential donor pool, by providing a near physiologic environment ultimately leading to decreased inflammation and rejection.
The EVLP technique is now routinely used clinically in Europe and North America. More than 300 lungs previously thought to be unusable have already been successfully transplanted using the method.
In the US, the process involves a 3-5 hours period during which the donated lungs are placed inside a sterile XVIVO Organ Chamber™ attached to a ventilator, pump and filters. The lungs are maintained at normal body temperature and perfused with STEEN Solution™, which is a colloid solution that contains nutrients, proteins and electrolytes, with or without red blood cells, depending upon choice of protocol. The warming and reperfusion period allows time for the lung to re-establish a near physiologic environment whilst the unique composition of the perfusate facilitates maintenance of homeostasis and removal of excess water in the lung. During the process, key indicators of lung function are evaluated continuously, e.g. gaseous exchange, airway pressure and lung compliance. When they are determined to be suitable, the lungs are transplanted into a waiting patient.
Advantages of EVLP include
- Lungs are ventilated during the warm EVLP process to assess efficacy of physiologic gaseous exchange under near physiologic conditions
- More time for preparation (to plan optimal timing of transplant surgery)
- More time to make sure the lungs meet acceptability criteria
- Increase the utilization of marginal/rejected donor lungs thereby expanding the donor pool
- Utilization of previously unacceptable lungs, as evidenced by the lung match runs provided from UNOS, thus increasing the donor pool and the choices available to patients on the waiting list.
- Utilization of DCD donor lungs, which are typically not transplanted in the US and were not previously transplanted in many of the investigational sites of the NOVEL and NOVEL Extension trial until the XPS™ became available via HDE Approval 2014.