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

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.

Study Overview

• Status: Terminated
• Conditions: Bronchiectasis; Emphysema; Pulmonary Fibrosis; Cystic Fibrosis; Alpha-1 Antitrypsin Deficiency; Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease (COPD); Sarcoidosis
• Intervention / Treatment: Device: Steen Solution™; Other: Conventional Lung Transplant

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• 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: 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 UNC Hospitals (UNCH) where they will have an ex-vivo CT scan. Lungs determined suitable will be offered to consented patients at UNCH 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30 Day Mortality	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.	30 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. * partial pressure of oxygen in the arterial blood (PaO2) ** fraction of inspired oxygen inspired oxygen fraction (FIO2)	24 and 72 hours post transplant.
ICU Length of Stay	The length of ICU stay is another standard research and clinical outcome assessment post transplant and has been selected as a secondary objective.	Time to Discharge.
Day 7 Ventilator/ECMO Status	7 days ventilator or extra-corporeal membrane oxygenator (ECMO free are being evaluated as secondary objectives.	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

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: November 12, 2010
• First Submitted That Met QC Criteria: November 15, 2010
• First Posted (Estimate): November 16, 2010

Study Record Updates

• Last Update Posted (Actual): July 13, 2018
• Last Update Submitted That Met QC Criteria: July 11, 2018
• Last Verified: July 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
• Other Study ID Numbers: UNC-001 Vitrolife

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes