Extending Preservation and Assessment Time of Donor Lungs Using the Toronto EVLP System™ at a Dedicated EVLP Facility

Lung Disease Clinical Trial

Official title:

A Phase 2, Multicenter, Open-label Study to Measure the Safety of Extending Preservation and Assessment Time of Donor Lungs Using Normothermic Ex Vivo Lung Perfusion and Ventilation (EVLP) as Administered by the SPONSOR Using the Toronto EVLP System™

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02234128
• Other study ID #: PXUS-14-001
• Secondary ID: 4766
• Status: Completed
• Phase: N/A
• Start date: July 18, 2015
• Est. completion date: November 7, 2019

Study information

• Verified date: November 2020
• Source: Lung Bioengineering Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a safety study to compare the safety of receiving a lung treated with the Toronto EVLP System™ by SPONSOR in SPONSOR's dedicated facility against standard lung transplantation.

Description:

Human donor lungs allocated to a participating study transplant center (Study Center) for a specific recipient and meeting study EVLP donor lung inclusion/exclusion criteria will be assessed by SPONSOR for inclusion into the study.

Upon retrieval, donor lung(s) will be packaged and transported on ice to the SPONSOR's EVLP facility in Silver Spring, Maryland, no differently than when lungs are recovered, packaged, and transported to any transplant center for implantation.

The EVLP procedure will be performed by Certified Ex Vivo Lung Specialists using the Toronto EVLP System™ for up to 6 hours, collecting and relaying lung function assessment data hourly or as requested by the Study Center transplant surgeon. Additionally, the Study Center surgeon will have the capability to evaluate lung function data and monitor the procedure remotely through a dedicated video link.

Upon acceptance of an EVLP donor lung by the Study Center, the single lung or lung block is cooled down by the Toronto EVLP System™ to 10 degrees C. Thereafter, perfusion and ventilation are stopped and the lung is prepared for hypothermic storage and transport to the accepting Study Center.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: November 7, 2019
• Est. primary completion date: November 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Subject Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Male or female patients

• All patients, 18 years of age or older

• Patient already on or added to the active waiting list for a single or bilateral lung transplant

• Patient or patient's representative provides informed consent for participation in the study at the time of study commencement or time of listing for transplant

• Patient or patient's representative reconfirms informed consent for the study on the day of lung transplant

Subject Exclusion Criteria:

A subject who meets any of the following criteria will be excluded from participation:

• Patients listed for same-side lung re-transplantation

• Patients listed for multiple organ transplantation including lung and any other organ

• Patients listed for live donor lobar transplant

• Patients with HIV, active Hepatitis B/C, or Burkholderia Cepacia

• Patients not initially consented into the study prior to the time of lung transplant

• Patients in the ICU at the time of initial lung offer requiring mechanical ventilation, ECMO or other Extracorporeal life support (ECLS).

Donor Lung Inclusion Criteria for EVLP Assessment:

The donor lung must meet at least one of the following criteria to proceed with EVLP:

• At the time of the clinical evaluation, the donor PaO2/FiO2 < 300 mmHg

• Donor received = 10 units of blood transfusions

• Donation after Cardiac Death (DCD) donor

• Expected cold ischemic time > 6 hours

• Donor age = 55 years old

• Study Center Investigator requires additional assessment ex vivo and/or extended preservation time

Donor Lung Exclusion Criteria for EVLP Assessment:

The donor lung is excluded from EVLP if at least one of the following criteria have been met:

• The donor lung has confirmed pneumonia and/or persistent purulent secretions identified via bronchoscopy

• Non-persistent purulent secretions that do not clear by hour 3 on EVLP

• The donor lung has confirmed evidence of aspiration

• The donor lung has significant mechanical lung injury or trauma

• The cold ischemic time, starting at donor aortic cross clamp/ initial flush (CIT-1), required to transport the lung from the donor site to start of the EVLP procedure at SPONSOR's facility > 10 hours

EVLP Lung Inclusion Criteria for Transplantation:

The donor lung must meet each of the following conditions post-EVLP for transplant suitability consideration by the Study Center Investigator:

• PvO2/FiO2 = 350 mmHg at final EVLP evaluation time period

• and < 15% increase from baseline value (defined as the first hour collection point) to final value of pulmonary vascular resistance (PVR)

• and < 15% increase from baseline value to final value of peak airway pressure (PawP)

• and < 15% decrease from baseline value to final value of static lung compliance (Cstat)

• and the total preservation time (TPT) does not exceed the following:

• the initial CIT-1 time from donor to EVLP > 1 hour and = 10 hours

• the EVLP time > 3 hours and = 6 hours

• the second CIT-2 from EVLP cool down to beginning of recipient implantation must be > 1 hour and = 6 hours for the first lung

• the second CIT-2 from EVLP cool down to beginning of recipient implantation must be > 1 hour and = 10 hours for the second lung

• and Study Center Investigator deems lung function suitable for intended subject

EVLP Lung Exclusion Criteria for Transplantation:

The donor lung is excluded from transplant inclusion if at least one of the following criteria have been met:

• PvO2/FiO2 < 350 mmHg at final EVLP evaluation time period

• or = 15% increase from baseline value to final value of pulmonary vascular resistance (PVR)

• or = 15% increase from baseline value to final value of peak airway pressure (PawP)

• or = 15% decrease from baseline value to final value of static lung compliance (Cstat)

• or TPT exceeds any of the following conditions:

• CIT-1 < 1 hour or > 10 hours

• EVLP < 3 hours or > 6 hours

• CIT-2 < 1 hour or > 6 hours for first lung or > 10 hours for second lung

• or Study Center investigator deems lung function unsuitable for intended subject

Related Conditions & MeSH terms

• Lung Disease
• Lung Diseases

Intervention

Device:
• Toronto EVLP System™
Extending preservation and assessment time of donor lungs using the Toronto EVLP System

Locations

Country	Name	City	State
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Loyola University Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke University Health System	Durham	North Carolina
United States	Inova Fairfax Medical Campus	Falls Church	Virginia
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	UPMC	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Lung Bioengineering Inc.

Country where clinical trial is conducted

United States, 

References & Publications (24)

Avlonitis VS, Wigfield CH, Golledge HD, Kirby JA, Dark JH. Early hemodynamic injury during donor brain death determines the severity of primary graft dysfunction after lung transplantation. Am J Transplant. 2007 Jan;7(1):83-90. — View Citation

Bennett M, Horton S, Thuys C, Augustin S, Rosenberg M, Brizard C. Pump-induced haemolysis: a comparison of short-term ventricular assist devices. Perfusion. 2004 Mar;19(2):107-11. — View Citation

Botha P, Trivedi D, Weir CJ, Searl CP, Corris PA, Dark JH, Schueler SV. Extended donor criteria in lung transplantation: impact on organ allocation. J Thorac Cardiovasc Surg. 2006 May;131(5):1154-60. — View Citation

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, Keshavjee S. The clinical potential of ex vivo lung perfusion. Expert Rev Respir Med. 2012 Feb;6(1):27-35. doi: 10.1586/ers.11.93. Review. — 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, Rubacha M, Yeung J, Hirayama S, Torbicki K, Madonik M, Fischer S, Hwang D, Pierre A, Waddell TK, de Perrot M, Liu M, Keshavjee S. Normothermic ex vivo perfusion prevents lung injury compared to extended cold preservation for transplantation. Am J Transplant. 2009 Oct;9(10):2262-9. doi: 10.1111/j.1600-6143.2009.02775.x. Epub 2009 Aug 6. — View Citation

Cypel M, Sato M, Yildirim E, Karolak W, Chen F, Yeung J, Boasquevisque C, Leist V, Singer LG, Yasufuku K, Deperrot M, Waddell TK, Keshavjee S, Pierre A. Initial experience with lung donation after cardiocirculatory death in Canada. J Heart Lung Transplant. 2009 Aug;28(8):753-8. doi: 10.1016/j.healun.2009.05.009. Epub 2009 Jun 28. — 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, Keshavjee S. Novel approaches to expanding the lung donor pool: donation after cardiac death and ex vivo conditioning. Clin Chest Med. 2011 Jun;32(2):233-44. doi: 10.1016/j.ccm.2011.02.003. Epub 2011 Mar 25. Review. — 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

Cypel M, Yeung JC, Machuca T, Chen M, Singer LG, Yasufuku K, de Perrot M, Pierre A, Waddell TK, Keshavjee S. Experience with the first 50 ex vivo lung perfusions in clinical transplantation. J Thorac Cardiovasc Surg. 2012 Nov;144(5):1200-6. doi: 10.1016/j.jtcvs.2012.08.009. Epub 2012 Aug 31. — View Citation

Kawut SM, Reyentovich A, Wilt JS, Anzeck R, Lederer DJ, O'Shea MK, Sonett JR, Arcasoy SM. Outcomes of extended donor lung recipients after lung transplantation. Transplantation. 2005 Feb 15;79(3):310-6. — View Citation

Koike T, Yeung JC, Cypel M, Rubacha M, Matsuda Y, Sato M, Waddell TK, Liu M, Keshavjee S. Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion. J Heart Lung Transplant. 2011 Dec;30(12):1312-9. doi: 10.1016/j.healun.2011.07.014. Epub 2011 Sep 17. — View Citation

Lyu DM, Zamora MR. Medical complications of lung transplantation. Proc Am Thorac Soc. 2009 Jan 15;6(1):101-7. doi: 10.1513/pats.200808-077GO. Review. — View Citation

Munshi L, Keshavjee S, Cypel M. Donor management and lung preservation for lung transplantation. Lancet Respir Med. 2013 Jun;1(4):318-28. doi: 10.1016/S2213-2600(12)70064-4. Epub 2013 Feb 20. Review. — View Citation

Orens JB, Boehler A, de Perrot M, Estenne M, Glanville AR, Keshavjee S, Kotloff R, Morton J, Studer SM, Van Raemdonck D, Waddel T, Snell GI; Pulmonary Council, International Society for Heart and Lung Transplantation. A review of lung transplant donor acceptability criteria. J Heart Lung Transplant. 2003 Nov;22(11):1183-200. Review. — View Citation

Pierre AF, Sekine Y, Hutcheon MA, Waddell TK, Keshavjee SH. Marginal donor lungs: a reassessment. J Thorac Cardiovasc Surg. 2002 Mar;123(3):421-7; discussion, 427-8. — View Citation

Suzuki Y, Cantu E, Christie JD. Primary graft dysfunction. Semin Respir Crit Care Med. 2013 Jun;34(3):305-319. doi: 10.1055/s-0033-1348474. Epub 2013 Jul 2. Review. — View Citation

Ware LB, Wang Y, Fang X, Warnock M, Sakuma T, Hall TS, Matthay M. Assessment of lungs rejected for transplantation and implications for donor selection. Lancet. 2002 Aug 24;360(9333):619-20. — View Citation

Watanabe N, Sakota D, Ohuchi K, Takatani S. Deformability of red blood cells and its relation to blood trauma in rotary blood pumps. Artif Organs. 2007 May;31(5):352-8. — View Citation

Wigfield CH, Cypel M, Yeung J, Waddell T, Alex C, Johnson C, Keshavjee S, Love RB. Successful emergent lung transplantation after remote ex vivo perfusion optimization and transportation of donor lungs. Am J Transplant. 2012 Oct;12(10):2838-44. doi: 10.1111/j.1600-6143.2012.04175.x. — View Citation

Yeung JC, Cypel M, Machuca TN, Koike T, Cook DJ, Bonato R, Chen M, Sato M, Waddell TK, Liu M, Slutsky AS, Keshavjee S. Physiologic assessment of the ex vivo donor lung for transplantation. J Heart Lung Transplant. 2012 Oct;31(10):1120-6. doi: 10.1016/j.healun.2012.08.016. — View Citation

Yeung JC, Cypel M, Waddell TK, van Raemdonck D, Keshavjee S. Update on donor assessment, resuscitation, and acceptance criteria, including novel techniques--non-heart-beating donor lung retrieval and ex vivo donor lung perfusion. Thorac Surg Clin. 2009 May;19(2):261-74. doi: 10.1016/j.thorsurg.2009.02.006. Review. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Count of Participants With Primary Graft Dysfunction (PGD), Grade 3	Primary Graft Dysfunction is a scale published by the International Society of Heart and Lung Transplantation that uses patient oxygenation and radiographic results to score patients on a 0 (zero) to 3 (three) scale, with 3 being the most significant dysfunction.	72 Hours
Primary	Count of Participants Surviving	The number of participants that survived to 30 days post-transplant.	30 Days
Secondary	PGD Score	PGD Score (0-3) at 0, 24, 48 & 72 hours post-transplant	0, 24, 48 & 72 Hours
Secondary	ICU Length of Stay		30 Days
Secondary	Total Lung Preservation Time (TPT)		72 Hours
Secondary	Time to First Extubation		Days
Secondary	Hospital Length of Stay		Days