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

NCT01615484 | Completed Results DMC

• 2 other identifiers: UNC-002 Vitrolife1UM1HL113115-01A1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• ICU Length of Stay

  Time to Discharge, up to 30 days

• Day 7 Ventilator/ECMO Status

  7 Days Post Transplant.

• Recipient Mortality at 12 Months

  12 months

• Bronchiolitis Obliterans Syndrome (BOS) Free Graft Survival

  12 Months

Study Arms (2)

Ex-vivo lung perfusion (EVLP) with STEEN Solution™

EXPERIMENTAL

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™; Device: STEEN Solution™

Lung transplant from conventional brain-dead organ donor

NO INTERVENTION

No experimental procedures will be carried out.

Interventions

Transplantation of lungs obtained from Non-Heart-Beating Donors (NHBDs) after ex-vivo perfusion w/ STEEN Solution™ PROCEDURE

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.

Ex-vivo lung perfusion (EVLP) with STEEN Solution™

STEEN Solution™ DEVICE

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.

Ex-vivo lung perfusion (EVLP) with STEEN Solution™

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Duke University: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Vitrolife: collaborator
• XVIVO Perfusion: collaborator

Study Sites (2)

UNC-Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (11)

• 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.

  PMID: 16818116 BACKGROUND

• 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.

  PMID: 19101308 BACKGROUND

• 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.

  PMID: 18954650 BACKGROUND

• 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.

  PMID: 19059112 BACKGROUND

• 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.

  PMID: 16564244 BACKGROUND

• 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.

  PMID: 16210116 BACKGROUND

• 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.

  PMID: 18852649 BACKGROUND

• 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.

  PMID: 19118301 BACKGROUND

• 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.

  PMID: 20368171 BACKGROUND

• 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.

  PMID: 21488765 BACKGROUND

• 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.

  PMID: 28945476 DERIVED

MeSH Terms

Conditions

Emphysema; Pulmonary Disease, Chronic Obstructive; Cystic Fibrosis; Pulmonary Fibrosis; Bronchiectasis; Sarcoidosis; Hypertension, Pulmonary; alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pancreatic Diseases; Digestive System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Lung Diseases, Interstitial; Fibrosis; Bronchial Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Liver Diseases; Subcutaneous Emphysema

Limitations and Caveats

Lungs recovered from 35 NHBDs, 22 had EVLP. Two lung blocks judged suitable, but not transplanted: no consented recipient available for #1, protocol time specifications could not be met for #2. As such, no subjects enrolled into EVLP arm.

Results Point of Contact

• Title: Thomas Egan, MD, MSc, FACS
• Organization: University of North Carolina at Chapel Hill

thomas_egan@med.unc.edu

919-966-3381

Study Officials

• Thomas M. Egan, MD, MSc.

  UNC-Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2012
• First Posted: June 8, 2012
• Study Start: September 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: January 1, 2017
• Last Updated: June 8, 2018
• Results First Posted: April 20, 2018

Record last verified: 2018-03

Locations

US (2)