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

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01615484
• Other study ID #: UNC-002 Vitrolife
• Secondary ID: 1UM1HL113115-01A
• Status: Completed
• Phase: N/A
• Start date: September 2013
• Est. completion date: January 2017

Study information

• Verified date: March 2018
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2017
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Alpha-1 Antitrypsin Deficiency
• Bronchiectasis
• Chronic Obstructive Pulmonary Disease (COPD)
• Cystic Fibrosis
• Emphysema
• Fibrosis
• Hypertension
• Hypertension, Pulmonary
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive
• Pulmonary Emphysema
• Pulmonary Fibrosis
• Pulmonary Hypertension
• Sarcoidosis

Intervention

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.

Locations

Country	Name	City	State
United States	UNC-Chapel Hill	Chapel Hill	North Carolina
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (5)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Duke University, National Heart, Lung, and Blood Institute (NHLBI), Vitrolife, XVIVO Perfusion

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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
Secondary	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.
Secondary	Recipient Mortality at 12 Months	Recipient mortality at 12 months post transplant is being evaluated as a secondary objective.	12 months
Secondary	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