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

NCT ID: NCT01365429

Last Updated: 2018-03-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

252 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-31

Study Completion Date

2020-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Lung Transplant

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

EVLP Group

EVLP Group are those recipient lung transplant patients that received donor lungs that had been placed on the XPS™ with Steen Solution™ and undergone ex-vivo lung perfusion before being transplanted.

Group Type EXPERIMENTAL

XPS™ with Steen Solution™

Intervention Type DEVICE

The XPS™ System is an integrated cardiac bypass system comprised of various components such as a Maquet CardioHelp centrifugal pump (K102726), the HicoVariotherm Heater/Cooler, the Hamilton C2 ICU (intensive care unit) pressure- controlled ventilator (K092148), the perfusate gas monitors, and the display monitors. The XPS™ System is responsible for housing the organ for preservation, providing the normothermic environment, and perfusing the organ with the STEEN Solution™. Donor lungs that meet inclusion criteria are placed on the XPS™ and rewarmed and perfused with STEEN Solution™ and ventilated for 3-6 hours. If the lungs meet transplant suitability, they are cooled down and transplanted into a consented recipient that meet's trial criteria.

Control Group

Control Group are those recipient lung transplant patients that receive donor lungs via conventional transplant.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

XPS™ with Steen Solution™

The XPS™ System is an integrated cardiac bypass system comprised of various components such as a Maquet CardioHelp centrifugal pump (K102726), the HicoVariotherm Heater/Cooler, the Hamilton C2 ICU (intensive care unit) pressure- controlled ventilator (K092148), the perfusate gas monitors, and the display monitors. The XPS™ System is responsible for housing the organ for preservation, providing the normothermic environment, and perfusing the organ with the STEEN Solution™. Donor lungs that meet inclusion criteria are placed on the XPS™ and rewarmed and perfused with STEEN Solution™ and ventilated for 3-6 hours. If the lungs meet transplant suitability, they are cooled down and transplanted into a consented recipient that meet's trial criteria.

Intervention Type DEVICE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

EVLP ex vivo lung perfusion

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

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 circulatory death donors.
* Investigator evaluation of donor lung as "unsuitable" for standard criteria for lung transplant. List reason for "unsuitable" determination.

1. Surgeon must be clinically satisfied with the lung evaluation (i.e.) overall improvement, if not, the reason for refusal must be listed.
2. Stability or improvement of other lung function parameters during EVLP perfusion - PVR, Compliance, Airway Pressures.
3. Two delta PO2 greater than 350 mmHg, if two delta PO2 mm Hg are not met than three out of four of the following parameters must be present:

* One delta PO2 of \> 350 or absolute PO2 of \> 400.
* Chest x-ray findings with absence or improvement of pulmonary edema/infiltrates
* Compliance static (greater than 35 single and greater than 60 for a double)
* Absence of consolidation by palpation

Exclusion Criteria

1. A recipient is HIV positive.
2. A recipient has active Hepatitis.
3. Investigator believes that the recipient has infection that excludes them from transplant in the study.
4. To receive multi-organ transplant.
5. Is on hemodialysis or has chronic severe renal dysfunction. Severe renal dysfunction is defined as a glomerular filtration rate of 29 or less (mL/min/1.73m2).
6. Is to have planned concurrent cardiac procedures.
7. A recipient is a re-transplant. (A re-transplant is defined as a recipient having the removal and transplant of a previously transplanted lung. A recipient with a previously single lung transplant is eligible to enroll in the trial if it is for the other lung and within 6 months of previous transplant.)
8. A recipient is on Nova Lung, ECMO, or on mechanical ventilation. (CPAP and BIPAP are not exclusionary)



1. Lung has significant pneumonia and/or persistent purulent secretions on bronchoscopy as determined by investigator.
2. Donor has known significant aspiration of gastric contents within the lung.
3. Donor lung has significant mechanical lung injury or trauma determined by chest x-ray, bronchoscopy, CT Scan or visual inspection.
4. Donor lung has active infectious disease such as HIV, Hepatitis B or C, HTLV or Syphilis. Note: This information is not available at the start of EVLP. Therefore this criteria can be assessed during or post EVLP, but prior to transplant.



1. All delta PO2 (s) are less than 350 mmHg (measured with a FiO2 set at 1.0) or all absolute PO2s are less than 400.
2. Overall greater than 10-15% Functional deterioration of other lung function across all parameters (PVR, Compliance, PawP) with chest x-ray findings showing deterioration.
3. Donor lung positive for infectious diseases such as HIV, Hepatitis B or C, or Syphilis.

Note: This information is not available until at the start of EVLP. Therefore this criteria can be assessed during or post EVLP, but prior to transplant.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

XVIVO Perfusion

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jaya Tiwari, BS, CCRP

Role: STUDY_DIRECTOR

XVIVO Perfusion, Inc

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

University of Florida-Gainesville

Gainesville, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Indiana University Health

Indianapolis, Indiana, United States

Site Status

University of Maryland

Baltimore, Maryland, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Henry Ford

Detroit, Michigan, United States

Site Status

Barnes Jewish Hospital

St Louis, Missouri, United States

Site Status

Columbia University Medical Centre

New York, New York, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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. doi: 10.1067/mtc.2002.120345.

Reference Type BACKGROUND
PMID: 11882811 (View on PubMed)

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. doi: 10.1164/ajrccm.163.1.2005093.

Reference Type BACKGROUND
PMID: 11208654 (View on PubMed)

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. doi: 10.1177/0310057X9502300107.

Reference Type BACKGROUND
PMID: 7778744 (View on PubMed)

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. doi: 10.1111/j.1600-6143.2006.01593.x.

Reference Type BACKGROUND
PMID: 17227559 (View on PubMed)

Botha P, Fisher AJ, Dark JH. Marginal lung donors: A diminishing margin of safety? Transplantation. 2006 Nov 27;82(10):1273-9. doi: 10.1097/01.tp.0000236099.52382.74.

Reference Type BACKGROUND
PMID: 17130774 (View on PubMed)

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. doi: 10.1097/01.tp.0000149504.53710.ae.

Reference Type BACKGROUND
PMID: 15699761 (View on PubMed)

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. doi: 10.1016/j.jtcvs.2005.12.037.

Reference Type BACKGROUND
PMID: 16678604 (View on PubMed)

Cohen RG, Starnes VA. Living donor lung transplantation. World J Surg. 2001 Feb;25(2):244-50. doi: 10.1007/s002680020025.

Reference Type BACKGROUND
PMID: 11338028 (View on PubMed)

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. doi: 10.1016/j.healun.2007.04.008. Epub 2007 Jun 13.

Reference Type BACKGROUND
PMID: 17613398 (View on PubMed)

Steen S, Sjoberg 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. doi: 10.1016/S0140-6736(00)04195-7.

Reference Type BACKGROUND
PMID: 11265950 (View on PubMed)

de Antonio DG, Marcos R, Laporta R, Mora G, Garcia-Gallo C, Gamez P, Cordoba M, Moradiellos J, Ussetti P, Carreno MC, Nunez JR, Calatayud J, Del Rio F, Varela A. Results of clinical lung transplant from uncontrolled non-heart-beating donors. J Heart Lung Transplant. 2007 May;26(5):529-34. doi: 10.1016/j.healun.2007.01.028.

Reference Type BACKGROUND
PMID: 17449425 (View on PubMed)

Steen S, Liao Q, Wierup PN, Bolys R, Pierre L, Sjoberg 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. doi: 10.1016/s0003-4975(03)00191-7.

Reference Type BACKGROUND
PMID: 12842550 (View on PubMed)

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. doi: 10.1016/j.athoracsur.2006.01.014.

Reference Type BACKGROUND
PMID: 16731122 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19632569 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18954650 (View on PubMed)

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. doi: 10.1016/s1053-2498(03)00096-2. No abstract available.

Reference Type BACKGROUND
PMID: 14585380 (View on PubMed)

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. doi: 10.1016/s0140-6736(02)09774-x.

Reference Type BACKGROUND
PMID: 12241936 (View on PubMed)

Steen S, Ingemansson R, Eriksson L, Pierre L, Algotsson L, Wierup P, Liao Q, Eyjolfsson A, Gustafsson R, Sjoberg T. First human transplantation of a nonacceptable donor lung after reconditioning ex vivo. Ann Thorac Surg. 2007 Jun;83(6):2191-4. doi: 10.1016/j.athoracsur.2007.01.033.

Reference Type BACKGROUND
PMID: 17532422 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19101308 (View on PubMed)

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. doi: 10.1097/01.sla.0000098625.24363.d9.

Reference Type BACKGROUND
PMID: 14631215 (View on PubMed)

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. doi: 10.1016/j.healun.2004.10.013.

Reference Type BACKGROUND
PMID: 16143259 (View on PubMed)

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. doi: 10.1111/j.1432-2277.2006.00318.x.

Reference Type BACKGROUND
PMID: 16764638 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16564244 (View on PubMed)

Wierup P, Haraldsson A, Nilsson F, Pierre L, Schersten H, Silverborn M, Sjoberg T, Westfeldt U, Steen S. Ex vivo evaluation of nonacceptable donor lungs. Ann Thorac Surg. 2006 Feb;81(2):460-6. doi: 10.1016/j.athoracsur.2005.08.015.

Reference Type BACKGROUND
PMID: 16427831 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19059112 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19663886 (View on PubMed)

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. doi: 10.1016/j.healun.2008.07.027. Epub 2008 Oct 1.

Reference Type BACKGROUND
PMID: 18971096 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19662970 (View on PubMed)

Van Raemdonck D, Neyrinck A, Verleden GM, Dupont L, Coosemans W, Decaluwe 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. doi: 10.1513/pats.200808-098GO.

Reference Type BACKGROUND
PMID: 19131528 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

VSS-NA-001, XVO-NA-002

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.