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

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.

Study Overview

• Status: Completed
• Conditions: Bronchiectasis; Emphysema; Pulmonary Fibrosis; Cystic Fibrosis; Alpha-1 Antitrypsin Deficiency; Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease (COPD); Sarcoidosis
• Intervention / Treatment: Procedure: Transplantation of lungs obtained from Non-Heart-Beating Donors (NHBDs) after ex-vivo perfusion w/ STEEN Solution™; Device: STEEN Solution™

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC-Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30 Day Mortality and Graft Survival	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.	30 Days
Primary Lung Graft Dysfunction (PGD)	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.	24 and 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU Length of Stay	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.	Time to Discharge, up to 30 days
Day 7 Ventilator/ECMO Status	Participants' status at Day 7 defined as the following: mechanical ventilation, extra-corporeal membrane oxygenator (ECMO), or extubated.	7 Days Post Transplant.
Recipient Mortality at 12 Months	Recipient mortality at 12 months post transplant is being evaluated as a secondary objective.	12 months
Bronchiolitis Obliterans Syndrome (BOS) Free Graft Survival	Bronchiolitis Obliterans Syndrome (BOS) free graft survival at 12 months is being used as a secondary outcome.	12 Months

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Duke University; Vitrolife; XVIVO Perfusion
• Investigators: Principal Investigator: Thomas M. Egan, MD, MSc., UNC-Chapel Hill

Publications and helpful links

General Publications

• Ingemansson R, Eyjolfsson A, Mared L, Pierre L, Algotsson L, Ekmehag B, Gustafsson R, Johnsson P, Koul B, Lindstedt S, Luhrs C, Sjoberg 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.
• 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. doi: 10.1016/j.healun.2004.11.049. Epub 2005 Jun 4. No abstract available.
• 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.
• 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.
• 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.
• 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. doi: 10.1016/j.healun.2006.03.011. No abstract available.
• 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.
• 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. doi: 10.1016/j.athoracsur.2005.09.034.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: June 6, 2012
• First Submitted That Met QC Criteria: June 6, 2012
• First Posted (Estimate): June 8, 2012

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: May 9, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Alpha-1 Antitrypsin Deficiency; Pulmonary Hypertension; Cystic Fibrosis; Bronchiectasis; Sarcoidosis; Emphysema; Chronic Obstructive Pulmonary Disease (COPD); Pulmonary Fibrosis; Lung Transplant
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Infant, Newborn, Diseases; Liver Diseases; Bronchial Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Subcutaneous Emphysema; Fibrosis; Hypertension; Bronchiectasis; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema; Pulmonary Fibrosis; Cystic Fibrosis; Alpha 1-Antitrypsin Deficiency; Hypertension, Pulmonary; Sarcoidosis; Pharmaceutical Solutions
• Other Study ID Numbers: UNC-002 Vitrolife; 1UM1HL113115-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided