Ex-vivo Perfusion and Ventilation of Lungs Recovered From Non-Heart-Beating Donors to Assess Transplant Suitability

• ClinicalTrials.gov Identifier: NCT01615484
• Recruitment Status: Completed
• First Posted: June 8, 2012
• Results First Posted: April 20, 2018
• Last Update Posted: June 8, 2018
• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Duke University; National Heart, Lung, and Blood Institute (NHLBI); Vitrolife; XVIVO Perfusion
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Study Description

Brief Summary:

The purpose of this research study is to learn about the safety of transplanting lungs obtained from non-heart-beating donors (NHBDs) 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.

Condition or disease	Intervention/treatment	Phase
Emphysema; Chronic Obstructive Pulmonary Disease (COPD); Cystic Fibrosis; Pulmonary Fibrosis; Bronchiectasis; Sarcoidosis; Pulmonary Hypertension; Alpha-1 Antitrypsin Deficiency	Procedure: Transplantation of lungs obtained from Non-Heart-Beating Donors (NHBDs) after ex-vivo perfusion w/ STEEN Solution™; Device: STEEN Solution™	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ex-vivo Perfusion and Ventilation of Lungs Recovered From Non-Heart-Beating Donors to Assess Transplant Suitability
• Study Start Date: September 2013
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: January 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ex-vivo lung perfusion (EVLP) 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.	Procedure: Transplantation of lungs obtained from Non-Heart-Beating Donors (NHBDs) 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 and Duke University Medical Center 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.
No Intervention: Lung transplant from conventional brain-dead organ donor; No experimental procedures will be carried out.

Outcome Measures

Primary Outcome Measures :

1. 30 Day Mortality and Graft Survival [ Time Frame: 30 Days ]
   The primary objective evaluated for this study is recipient mortality and graft survival at 30 days post transplant. 30 day mortality and graft survival is used as a standard research assessment to evaluate post transplant outcomes.
2. Primary Lung Graft Dysfunction (PGD) [ Time Frame: 24 and 72 hours ]

   Primary Lung Graft Dysfunction (PGD) is an indicator for significant morbidity and mortality after lung transplantation.

   Grade 0: PaO2/FIO2 > 300 with normal chest radiograph; Grade 1: PaO2/FIO2 > 300 with diffuse infiltrates on the chest radiograph; Grade 2: PaO2/FIO2 between 200 and 300; Grade 3: PaO2/FIO2 < 200.

Secondary Outcome Measures :

1. ICU Length of Stay [ Time Frame: Time to Discharge, up to 30 days ]
   The length of ICU stay in days is another standard research and clinical outcome assessment post transplant and has been selected as a secondary objective.
2. Day 7 Ventilator/ECMO Status [ Time Frame: 7 Days Post Transplant. ]
   Participants' status at Day 7 defined as the following: mechanical ventilation, extra-corporeal membrane oxygenator (ECMO), or extubated.
3. Recipient Mortality at 12 Months [ Time Frame: 12 months ]
   Recipient mortality at 12 months post transplant is being evaluated as a secondary objective.
4. Bronchiolitis Obliterans Syndrome (BOS) Free Graft Survival [ Time Frame: 12 Months ]
   Bronchiolitis Obliterans Syndrome (BOS) free graft survival at 12 months is being used as a secondary outcome.

Eligibility Criteria

• Ages Eligible for Study: 15 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 transplant at UNC or Duke
• Male or Female, 15 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.

Exclusion Criteria:

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

Contacts and Locations

Locations

United States, North Carolina

UNC-Chapel Hill

Chapel Hill, North Carolina, United States, 27599

Duke University Medical Center

Durham, North Carolina, United States, 27710

Sponsors and Collaborators

University of North Carolina, Chapel Hill

Duke University

National Heart, Lung, and Blood Institute (NHLBI)

Vitrolife

XVIVO Perfusion

Investigators

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

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.

Cypel M, Yeung JC, Liu M, Anraku M, Chen F, Karolak W, Sato M, Laratta J, Azad S, Madonik M, Chow CW, Chaparro C, Hutcheon M, Singer LG, Slutsky AS, Yasufuku K, de Perrot M, Pierre AF, Waddell TK, Keshavjee S. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med. 2011 Apr 14;364(15):1431-40. doi: 10.1056/NEJMoa1014597.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Egan T, Blackwell J, Birchard K, Haithcock B, Long J, Gazda S, Casey N, Thys C. Assessment of Lungs for Transplant Recovered from Uncontrolled Donation after Circulatory Determination of Death Donors. Ann Am Thorac Soc. 2017 Sep;14(Supplement_3):S251. doi: 10.1513/AnnalsATS.201609-687MG.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT01615484
• Other Study ID Numbers: UNC-002 Vitrolife; 1UM1HL113115-01A1 ( U.S. NIH Grant/Contract )
• First Posted: June 8, 2012
• Results First Posted: April 20, 2018
• Last Update Posted: June 8, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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:

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