Phase 2 Study of Ex-vivo Perfusion and Ventilation of Lungs to Assess Transplant Suitability

• Primary Lung Graft Dysfunction (PGD) [ Time Frame: 24 and 72 hours post transplant. ] [ Designated as safety issue: Yes ]
  Primary Lung Graft Dysfunction (PGD) is an indicator for significant morbidity and mortality after lung transplantation. PGD at 24 and 72 hours post LTX are secondary objectives.
• ICU Length of Stay [ Time Frame: Time to Discharge. ] [ Designated as safety issue: Yes ]
  The length of ICU stay is another standard research and clinical outcome assessment post transplant and has been selected as a secondary objective.
• Day 7 Ventilator/ECMO Status [ Time Frame: 7 Days Post Transplant. ] [ Designated as safety issue: Yes ]
  7 days ventilator or extra-corporeal membrane oxygenator (ECMO free are being evaluated as secondary objectives.
• Recipient mortality at 12 months. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  Recipient mortality at 12 months post transplant is being evaluated as a secondary objective.

The purpose of this research study is to learn about the safety of transplanting lungs that have been ventilated (attached to a breathing machine or ventilator to deliver oxygen) and perfused with a lung perfusion solution (Steen solution™, made by Vitrolife). This ventilation and perfusion will be done outside the body (ex-vivo) in a modified cardiopulmonary bypass circuit (the kind of device used routinely during most heart surgeries). The purpose of performing ex-vivo perfusion and ventilation is to learn how well the lungs work, and whether they are likely safe to transplant.

• Emphysema
• Chronic Obstructive Pulmonary Disease (COPD)
• Cystic Fibrosis
• Pulmonary Fibrosis
• Bronchiectasis
• Sarcoidosis
• Pulmonary Hypertension
• Alpha-1 Antitrypsin Deficiency

• Procedure: Transplantation of Lungs After Ex-vivo Perfusion w/ STEEN Solution™
  After EVLP, lungs will be cooled in the circuit to room temperature, then flushed with cold Perfadex™, and taken to UNCH where they will have an ex-vivo CT scan. Lungs determined suitable will be offered to consented patients at UNC Hospitals based on Lung Allocation Score. Lungs not considered for transplantation may be subjected to different experiments but are not to be a part of this research study. In summary, lungs with good and stable function during EVLP will be transplanted into recipients as per current clinical practice.
• Device: Steen Solution™
  This solution is a buffered dextran and albumin-containing extracellular perfusate with an optimal colloid osmotic pressure developed specifically for extra-corporeal perfusion of lungs.

• Experimental: Ex-vivo Lung Perfusion with STEEN Solution™
  The perfusion of the lungs will be performed using STEEN Solution™. The lungs will be physiologically assessed during ex vivo perfusion with STEEN Solution™ perfusate.
  Interventions:

  • Procedure: Transplantation of Lungs After Ex-vivo Perfusion w/ STEEN Solution™
  • Device: Steen Solution™
• No Intervention: Lung transplant from conventional brain-dead organ donor
  No experimental procedures will be carried out.

• Orens JB, Estenne M, Arcasoy S, Conte JV, Corris P, Egan JJ, Egan T, Keshavjee S, Knoop C, Kotloff R, Martinez FJ, Nathan S, Palmer S, Patterson A, Singer L, Snell G, Studer S, Vachiery JL, Glanville AR; Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2006 Jul;25(7):745-55.
• Ingemansson R, Eyjolfsson A, Mared L, Pierre L, Algotsson L, Ekmehag B, Gustafsson R, Johnsson P, Koul B, Lindstedt S, Lührs C, Sjöberg T, Steen S. Clinical transplantation of initially rejected donor lungs after reconditioning ex vivo. Ann Thorac Surg. 2009 Jan;87(1):255-60. doi: 10.1016/j.athoracsur.2008.09.049.
• Mason DP, Thuita L, Alster JM, Murthy SC, Budev MM, Mehta AC, Pettersson GB, Blackstone EH. Should lung transplantation be performed using donation after cardiac death? The United States experience. J Thorac Cardiovasc Surg. 2008 Oct;136(4):1061-6. doi: 10.1016/j.jtcvs.2008.04.023.
• Cypel M, Yeung JC, Hirayama S, Rubacha M, Fischer S, Anraku M, Sato M, Harwood S, Pierre A, Waddell TK, de Perrot M, Liu M, Keshavjee S. Technique for prolonged normothermic ex vivo lung perfusion. J Heart Lung Transplant. 2008 Dec;27(12):1319-25. doi: 10.1016/j.healun.2008.09.003.
• Egan TM, Haithcock JA, Nicotra WA, Koukoulis G, Inokawa H, Sevala M, Molina PL, Funkhouser WK, Mattice BJ. Ex vivo evaluation of human lungs for transplant suitability. Ann Thorac Surg. 2006 Apr;81(4):1205-13.
• Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D; ISHLT Working Group on Primary Lung Graft Dysfunction. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2005 Oct;24(10):1454-9. Epub 2005 Jun 4.
• Kim IK, Bedi DS, Denecke C, Ge X, Tullius SG. Impact of innate and adaptive immunity on rejection and tolerance. Transplantation. 2008 Oct 15;86(7):889-94. doi: 10.1097/TP.0b013e318186ac4a. Review.
• Moers C, Smits JM, Maathuis MH, Treckmann J, van Gelder F, Napieralski BP, van Kasterop-Kutz M, van der Heide JJ, Squifflet JP, van Heurn E, Kirste GR, Rahmel A, Leuvenink HG, Paul A, Pirenne J, Ploeg RJ. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009 Jan 1;360(1):7-19. doi: 10.1056/NEJMoa0802289.
• Cypel M, Liu M, Rubacha M, Yeung JC, Hirayama S, Anraku M, Sato M, Medin J, Davidson BL, de Perrot M, Waddell TK, Slutsky AS, Keshavjee S. Functional repair of human donor lungs by IL-10 gene therapy. Sci Transl Med. 2009 Oct 28;1(4):4ra9. doi: 10.1126/scitranslmed.3000266.

Lung Recipient Inclusion Criteria:

• A recipient must meet the following requirement to enroll into the study:
• Requires a single or bilateral lung transplant and is listed for lung transplant at UNC.
• Male or Female, 18 years of age or older.
• Subject or Subject's Representative provides a legally effective informed consent.
• Recipient does not have HIV, active Hepatitis or is colonized with Burkholderia cepacia.
• Potential subjects who have undergone previous lung transplants and meet all other inclusion criteria are eligible for study participation.

Lung Recipient Exclusion Criteria:

• Recipient fails to meet standard of care requirements for lung transplant, or decides not to participate.

• Vitrolife
• XVIVO Perfusion