Novel Lung Trial: Normothermic Ex Vivo Lung Perfusion (Evlp) As An Assessment Of Extended/Marginal Donor Lungs - Full Text View

Purpose

Human donor lungs that do not meet the standard clinical criteria for donor lung utilization but fit into the study inclusion criteria will be retrieved from the donor using current donor lung retrieval techniques.

Condition	Intervention	Phase
Transplantation, Lungs	Drug: Ex vivo lung perfusion with Steen Solution™	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Novel Lung Trial: Normothermic Ex Vivo Lung Perfusion (Evlp) As An Assessment Of Extended/Marginal Donor Lungs

Resource links provided by NLM:

MedlinePlus related topics: Lung Transplantation

U.S. FDA Resources

Further study details as provided by XVIVO Perfusion:

Primary Outcome Measures:

30 Day Mortality [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
Mortality at 30 days post transplant.

Secondary Outcome Measures:

PGD Scores at 0,24,and 72 hours [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
Primary Lung Graft Dysfunction (PGD) is an indicator for significant morbidity and mortality after lung transplantation. PGD is assessed at 0, 24 and 72 hours post operative by the Surgeon using the following scale/categories 0-1, 2, and 3, refer to Appendix III. The 72 hour assessment is analyzed as a secondary objective.
Intensive Care Unit Stay [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
Length of ICU stay post transplant
Day 7 Ventilator/ECMO Status [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
Ventilator status and extra-corporeal membrane oxygenator (ECMO) free is assessed seven days after transplant.
12 Month Survival [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
12 month subject's survival status shall be evaluated.

Estimated Enrollment:	84
Study Start Date:	May 2011
Estimated Study Completion Date:	May 2014
Estimated Primary Completion Date:	May 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: EVLP Group EVLP Group are those recipient lung transplant patients that received donor lungs that had been placed on the ex vivo lung perfusion system with Steen Solution™ .	Drug: Ex vivo lung perfusion with Steen Solution™ The circuit is primed with 2,000cc Steen Solution™. At one hour of EVLP, 500 cc of circulated perfusate was removed and replenished with 500 cc of fresh perfusate. After that, 250 cc of perfusate was exchanged every hour. Other Name: EVLP
No Intervention: Control Group Control Group are those recipient lung transplant patients that receive donor lungs via conventional transplant.

Detailed Description:

These lungs will be brought to the study transplant center to be re-assessed by the transplant team. The lungs will be physiologically assessed during ex vivo perfusion with Steen Solution. Perfusion of these lungs will be performed using Steen solution with the addition of methylprednisolone, heparin and antibiotics. With respect to the decision of lung utilization those organs with a delta pO2 (Δ pO2 = Pulmonary vein pO2 - pulmonary artery pO2) during ex vivo perfusion assessment > 350mmHg, good lung compliance, and a favorable opinion of the transplant surgeon will be considered transplantable. Lungs will be excluded for transplantation: if the Δ pO2 is less than 350mmHg or if they demonstrate >10% deterioration in any of the following functional parameters: pulmonary vascular resistance (PVR), dynamic compliance or airway pressures. Lungs will also be excluded if they are deemed unsuitable based on the clinical judgment of the lung transplant surgeon.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Recipient Inclusion/Exclusion Criteria The recipient inclusion/exclusion criteria apply to patients enrolled in the control or EVLP treatment arms.

Recipient Inclusion Criteria
1. Requires single or bilateral lung transplant.
2. Male or Female, 18 years of age or older.
3. Subject or Subject's Representative provides a legally effective informed consent.
Recipient exclusion Criteria
1. A recipient is HIV positive.
2. A recipient has active Hepatitis.
3. A recipient has Burkholderia cepacia.
4. A recipient is a re-transplant. A re-transplant is defined as a recipient having removal of a previously transplanted lung. A recipient with a previously singled transplant is eligible to enroll in the trial if it is the other lung.
5. A recipient is on Nova Lung, ECMO, or on mechanical ventilation.

Donor Inclusion/Exclusion Criteria for EVLP Assessment

Donor Inclusion Criteria
1. The Donor lung must meet the following criteria to proceed with EVLP:
2. At the time of the clinical evaluation , the PaO2/FiO2 ≤ 300mmHg Or If PaO2/FiO2 > 30mmHg and the donor has any one or more of the following donor risk factors:
  - Multiple blood transfusions.
  - Pulmonary edema detected via CXR, bronchoscopy or palpation of lungs.
  - Donation after cardiac death donors.
  - Investigator evaluation of donor lung as "unsuitable" for standard criteria for lung transplant. List reason for "unsuitable" determination.
Donor Exclusion Criteria
1. lung has significant pneumonia and/or persistent purulent secretions on bronchoscopy as determined by investigator.
2. Donor has aspirated gastric contents in to the lung. Donor lung has significant mechanical lung injury or trauma.
3. Donor lung has active infectious disease such as HIV, Hepatitis B or C, HTLV or Syphilis.

Donor Inclusion/Exclusion Criteria for Transplant Suitability after EVLP

Donor Inclusion Criteria for Transplant Suitability
1. Δ PaO2 greater than 350 mmHg (measured with an FiO2 set at 1.0) at two consecutive time periods at 2h, 3h or 4h of ex vivo perfusion.
2. Stability or improvement of other lung function parameters during EVLP perfusion -PVR, Compliance, Airway Pressures.
3. Surgeon clinically satisfied with lung evaluation. If not provide a reason.
Donor Exclusion Criteria for Transplant Suitability after EVLP
1. Δ PaO2 less than 350 mmHg (measured with an FiO2 set at 1.0) at two consecutive time periods at 2h, 3h , or 4h of ex vivo perfusion
2. >10% Functional deterioration of other lung function parameters (PVR, Compliance, PawP).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01365429

Locations

United States, Colorado
University of Colorado	Recruiting
Aurora, Colorado, United States, 80045
Contact: Michael Weyant, MD 303-724-2800 Michael.Weyant@ucdenver.edu
Contact: Tracey MacDermott 303-724-2757 Tracey.MacDermott@ucdenver.edu
Principal Investigator: Michael Weyant, MD
United States, Indiana
Indiana University Health	Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Annie Thorp, RN, BSN, CCRC 317-962-9904 athorp2@iuhealth.org
Contact: Thomas Wozniak, MD 317-923-1787 TWozniak@IUHealth.org
Principal Investigator: Thomas Wozniak, MD
United States, Maryland
University of Maryland	Recruiting
Balitmore, Maryland, United States, 21201
Contact: Bartley Griffith, MD 410-328-3822 bgriffith@smail.umaryland.edu
Contact: Dana Beach, BSN, CCRC 410-328-0993 DBeach2@smail.umaryland.edu
Principal Investigator: Bartley Griffith, MD
United States, Massachusetts
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Phillip Camp, MD 617-732-7696 PCAMP@PARTNERS.ORG
Contact: Katherine Armstrong, MPH 617-732-5690 karmstrong5@partners.org
Principal Investigator: Phillip Camp, MD
United States, New York
Columbia University Medical Centre	Recruiting
New York, New York, United States, 10032
Contact: Frank D'ovidio, MD 212-342-5226 fd2133@columbia.edu
Contact: Lyn Goldsmith, MA,RN,BSN,CCRC (212) 342-0261 lg2240@columbia.edu
Principal Investigator: Frank D'Ovidio, MD
United States, North Carolina
Duke University	Recruiting
Durham, North Carolina, United States, 27710
Contact: Robert Davis, MD 919-681-4760 davis053@mc.duke.edu
Contact: Jason Hawkins 919-681-5775 jason.hawkins@duke.edu
Principal Investigator: Robert Davis, MD
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Edward Cantu, MD 215-615-6582 Edward.Cantu@uphs.upenn.edu
Contact: Jaya Tiwari 215-834-6525 Jaya.Tiwari@uphs.upenn.edu
Principal Investigator: Edward Cantu, MD

Sponsors and Collaborators

XVIVO Perfusion

More Information

Publications:

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.

Fisher AJ, Donnelly SC, Hirani N, Haslett C, Strieter RM, Dark JH, Corris PA. Elevated levels of interleukin-8 in donor lungs is associated with early graft failure after lung transplantation. Am J Respir Crit Care Med. 2001 Jan;163(1):259-65.

Power BM, Van Heerden PV. The physiological changes associated with brain death--current concepts and implications for treatment of the brain dead organ donor. Anaesth Intensive Care. 1995 Feb;23(1):26-36. Review.

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.

Botha P, Fisher AJ, Dark JH. Marginal lung donors: A diminishing margin of safety? Transplantation. 2006 Nov 27;82(10):1273-9.

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.

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.

Cohen RG, Starnes VA. Living donor lung transplantation. World J Surg. 2001 Feb;25(2):244-50.

Yamane M, Date H, Okazaki M, Toyooka S, Aoe M, Sano Y. Long-term improvement in pulmonary function after living donor lobar lung transplantation. J Heart Lung Transplant. 2007 Jul;26(7):687-92. Epub 2007 Jun 13.

Steen S, Sjöberg T, Pierre L, Liao Q, Eriksson L, Algotsson L. Transplantation of lungs from a non-heart-beating donor. Lancet. 2001 Mar 17;357(9259):825-9.

de Antonio DG, Marcos R, Laporta R, Mora G, García-Gallo C, Gámez P, Córdoba M, Moradiellos J, Ussetti P, Carreño MC, Núñez JR, Calatayud J, Del Río F, Varela A. Results of clinical lung transplant from uncontrolled non-heart-beating donors. J Heart Lung Transplant. 2007 May;26(5):529-34.

Steen S, Liao Q, Wierup PN, Bolys R, Pierre L, Sjöberg T. Transplantation of lungs from non-heart-beating donors after functional assessment ex vivo. Ann Thorac Surg. 2003 Jul;76(1):244-52; discussion 252.

Snell GI, Oto T, Levvey B, McEgan R, Mennan M, Higuchi T, Eriksson L, Williams TJ, Rosenfeldt F. Evaluation of techniques for lung transplantation following donation after cardiac death. Ann Thorac Surg. 2006 Jun;81(6):2014-9.

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. Epub 2009 Jun 28.

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.

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. No abstract available.

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.

Steen S, Ingemansson R, Eriksson L, Pierre L, Algotsson L, Wierup P, Liao Q, Eyjolfsson A, Gustafsson R, Sjöberg T. First human transplantation of a nonacceptable donor lung after reconditioning ex vivo. Ann Thorac Surg. 2007 Jun;83(6):2191-4.

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.

Rega FR, Jannis NC, Verleden GM, Lerut TE, Van Raemdonck DE. Long-term preservation with interim evaluation of lungs from a non-heart-beating donor after a warm ischemic interval of 90 minutes. Ann Surg. 2003 Dec;238(6):782-92; discussion 792-3.

Rega FR, Wuyts WA, Vanaudenaerde BM, Jannis NC, Neyrinck AP, Verleden GM, Lerut TE, Van Raemdonck DE. Nebulized N-acetyl cysteine protects the pulmonary graft inside the non-heart-beating donor. J Heart Lung Transplant. 2005 Sep;24(9):1369-77.

Erasmus ME, Fernhout MH, Elstrodt JM, Rakhorst G. Normothermic ex vivo lung perfusion of non-heart-beating donor lungs in pigs: from pretransplant function analysis towards a 6-h machine preservation. Transpl Int. 2006 Jul;19(7):589-93.

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.

Wierup P, Haraldsson A, Nilsson F, Pierre L, Scherstén H, Silverborn M, Sjöberg T, Westfeldt U, Steen S. Ex vivo evaluation of nonacceptable donor lungs. Ann Thorac Surg. 2006 Feb;81(2):460-6.

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.

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. Epub 2009 Aug 6.

Inci I, Ampollini L, Arni S, Jungraithmayr W, Inci D, Hillinger S, Leskosek B, Vogt P, Weder W. Ex vivo reconditioning of marginal donor lungs injured by acid aspiration. J Heart Lung Transplant. 2008 Nov;27(11):1229-36. Epub 2008 Oct 1.

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. Review.

Van Raemdonck D, Neyrinck A, Verleden GM, Dupont L, Coosemans W, Decaluwé H, Decker G, De Leyn P, Nafteux P, Lerut T. Lung donor selection and management. Proc Am Thorac Soc. 2009 Jan 15;6(1):28-38. Review.

Responsible Party:	XVIVO Perfusion
ClinicalTrials.gov Identifier:	NCT01365429 History of Changes
Other Study ID Numbers:	VSS-NA-001
Study First Received:	June 2, 2011
Last Updated:	April 5, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by XVIVO Perfusion:

Lung Transplant, Transplantation Lung

ClinicalTrials.gov processed this record on May 22, 2013