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

Purpose

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.

Condition	Intervention	Phase
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™ Device: Steen Solution™	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase 2 Study of Ex-vivo Perfusion and Ventilation of Lungs to Assess Transplant Suitability

Resource links provided by NLM:

Genetics Home Reference related topics: alpha-1 antitrypsin deficiency cystic fibrosis

MedlinePlus related topics: Alpha-1 Antitrypsin Deficiency COPD Cystic Fibrosis Emphysema High Blood Pressure Lung Transplantation Pulmonary Fibrosis Pulmonary Hypertension Sarcoidosis

Genetic and Rare Diseases Information Center resources: Alpha 1-antitrypsin Deficiency Cystic Fibrosis

U.S. FDA Resources

Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:

30 Day Mortality [ Time Frame: 30 Days ] [ Designated as safety issue: Yes ]
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:

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.


Estimated Enrollment:	20
Study Start Date:	December 2010
Estimated Study Completion Date:	July 2017
Estimated Primary Completion Date:	July 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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.
No Intervention: Lung transplant from conventional brain-dead organ donor No experimental procedures will be carried out.

Arms

Assigned Interventions

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.

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.

No Intervention: Lung transplant from conventional brain-dead organ donor

No experimental procedures will be carried out.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241942

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

Additional Information:

Organ Procurement and Transplantation Network web site (National Data/ Waiting List Removals/ Lung/ Removal Reasons by Year) This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

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:	Tom Egan, MD,MsC, Professor of Surgery, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:	NCT01241942 History of Changes
Other Study ID Numbers:	UNC-001 Vitrolife
Study First Received:	November 12, 2010
Last Updated:	May 2, 2014
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

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:


Alpha 1-Antitrypsin Deficiency Bronchiectasis Cystic Fibrosis Fibrosis Hypertension Hypertension, Pulmonary Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Pulmonary Fibrosis Bronchial Diseases Cardiovascular Diseases Digestive System Diseases	Emphysema Genetic Diseases, Inborn Infant, Newborn, Diseases Liver Diseases Pancreatic Diseases Pathologic Processes Respiratory Tract Diseases Subcutaneous Emphysema Vascular Diseases Pharmaceutical Solutions Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015