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

Study Description

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Brief Summary:

The purpose of this research study is to perfect the technique of EVLP and 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 lung perfusion and ventilation (EVLP) is to learn how well the lungs work, and whether they are likely safe to transplant.

Condition or disease	Intervention/treatment	Phase
Emphysema; Chronic Obstructive Pulmonary Disease (COPD); Cystic Fibrosis; Pulmonary Fibrosis; Bronchiectasis; Sarcoidosis; Pulmonary Hypertension; Alpha-1 Antitrypsin Deficiency	Device: Steen Solution™; Other: Conventional Lung Transplant	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	103 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Device Feasibility
Official Title:	Phase 2 Study of Ex-vivo Perfusion and Ventilation of Lungs to Assess Transplant Suitability
Study Start Date :	December 2010
Actual Primary Completion Date :	December 2012
Actual Study Completion Date :	June 2013

Arms and Interventions

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Arm	Intervention/treatment
Experimental: EVLP with STEEN Solution™; The perfusion of the lungs will be performed using STEEN Solution™ and then physiologically assessed. Lungs deemed suitable will be transplanted after Ex-vivo Perfusion w/ STEEN Solution™.	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. 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 with Steen Solution™ will be transplanted into recipients as per current clinical practice.
Active Comparator: Conventional Lung transplant; No experimental procedures will be carried out. Lungs from conventional brain-dead organ donors will be used for transplant.	Other: Conventional Lung Transplant; No experimental procedures will be carried out. Lungs from conventional brain-dead organ donors will be used for transplant.

Outcome Measures

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Primary Outcome Measures :

1. 30 Day Mortality [ Time Frame: 30 Days ]
   The primary objective evaluated for this study is recipient mortality at 30 days post transplant. 30 day mortality is used as a standard research assessment to evaluate post transplant outcomes.

Secondary Outcome Measures :

1. Primary Lung Graft Dysfunction (PGD) [ Time Frame: 24 and 72 hours post transplant. ]
   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.
2. ICU Length of Stay [ Time Frame: Time to Discharge. ]
   The length of ICU stay is another standard research and clinical outcome assessment post transplant and has been selected as a secondary objective.
3. Day 7 Ventilator/ECMO Status [ Time Frame: 7 Days Post Transplant. ]
   7 days ventilator or extra-corporeal membrane oxygenator (ECMO free are being evaluated as secondary objectives.
4. Recipient mortality at 12 months. [ Time Frame: 12 months ]
   Recipient mortality at 12 months post transplant is being evaluated as a secondary objective.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, North Carolina
UNC Hospitals
Chapel Hill, North Carolina, United States, 27599

Sponsors and Collaborators

University of North Carolina, Chapel Hill

Vitrolife

XVIVO Perfusion

Investigators

Principal Investigator:	Thomas M. Egan, MD, MSc.	UNC-Chapel Hill

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

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.

Responsible Party:	University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:	NCT01241942 History of Changes
Other Study ID Numbers:	UNC-001 Vitrolife
First Posted:	November 16, 2010
Last Update Posted:	February 6, 2017
Last Verified:	July 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		Yes
Device Product Not Approved or Cleared by U.S. FDA:		No

Keywords provided by University of North Carolina, Chapel Hill:

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

Additional relevant MeSH terms:

Hypertension; Lung Diseases; Fibrosis; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Cystic Fibrosis; Hypertension, Pulmonary; Pulmonary Fibrosis; Emphysema; Pulmonary Emphysema; Sarcoidosis; Bronchiectasis; Alpha 1-Antitrypsin Deficiency; Vascular Diseases	Cardiovascular Diseases; Respiratory Tract Diseases; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Bronchial Diseases; Liver Diseases; Subcutaneous Emphysema; Pharmaceutical Solutions