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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by XVIVO Perfusion
Sponsor:
Information provided by (Responsible Party):
XVIVO Perfusion
ClinicalTrials.gov Identifier:
NCT01365429
First received: June 2, 2011
Last updated: March 2, 2015
Last verified: July 2014
  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
Lung Transplant
Device: 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:


Further study details as provided by XVIVO Perfusion:

Primary Outcome Measures:
  • PAS Study Primary Endpoint [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]

    The primary end point is a co-primary endpoint comparing survival rates and rates of grade 3 PGD at 72 hours with success if and only if both endpoints are met.

    Treatment Group (T) = EVLP transplant subjects Control Group (C) = standard transplant subjects

    Co-Primary Endpoints:

    Endpoint #1: Survival of T is non-inferior to C Ho: C - T ≥ M1 (T is inferior to the control by M1 or more) Ha: C - T < M1 (T is inferior to the control by less than M1) where M1 = 0.12 Endpoint #2: Rate of grade 3 PGD at 72 hours for T is non-inferior to the rate for C Ho: C - T ≥ M2 Ha: C - T < M2 where M2 = 0.12


  • PMA Study Primary Endpoint [ Time Frame: 72hrs and Survival ] [ Designated as safety issue: Yes ]

    The primary end point is non-inferiority of the 3-year survival rate of the EVLP group as compared to 3-year survival rate of the control group.

    Ho: C - T ≥ M3 (T is inferior to the control by M3 or more) Ha: C - T < M3 (T is inferior to the control by less than M3) where M3 = 0.12



Secondary Outcome Measures:
  • PMA Secondary Endpoints [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]

    Primary Lung Graft Dysfunction (PGD) is an indicator for significant morbidity The PMA secondary endpoints are as follows:

    • FEV1 at 3 mos, 6 mos, 9 mos, and 1 yr
    • PGD score at 24 and 48 hrs
    • ICU LOS
    • Hospital LOS
    • Use of ECMO due to lung function post transplant
    • Duration of mechanical ventilation post transplant
    • Quality of Life and functional status at one year

  • PAS Secondary End Point: [ Time Frame: 5 Years ] [ Designated as safety issue: No ]

    Quality of Life measured by functional status, physical capability, and employment limitations.

    • Episodes of rejection per UNOS registry
    • FEV1 at 1, 2, 3, 4, and 5 years


Estimated Enrollment: 104
Study Start Date: May 2011
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2017 (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™ .
Device: 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.

  1. 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.
  2. Recipient 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)

Donor Inclusion/Exclusion Criteria for EVLP Assessment

  1. 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.
  2. 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

  1. Donor Inclusion Criteria for Transplant Suitability

    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
  2. Donor Exclusion Criteria for Transplant Suitability after EVLP

    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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 Completed
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Mary Maliarik, PhD, CCRC    734-615-8627    marymali@med.umich.edu   
Principal Investigator: William Lynch, MD         
Henry Ford Recruiting
Detroit, Michigan, United States, 4822
Contact: Wilma Ruffin, BA, BS, M.Ed    313-916-7506    Wruffin1@hfhs.org   
Principal Investigator: Hassan Nemeh, MD         
Spectrum Health Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Marianne Morrissey, RN, BSN    616-391-1129    marianne.morrissey@spectrumhealth.org   
Principal Investigator: Edward Murphy, MD         
United States, Missouri
Barnes Jewish Hospital Recruiting
St. Louis, Missouri, United States, 63110
Contact: Jennifer Bell, RN, BSN    314-747-6969    bellj@wudosis.wustl.edu   
Principal Investigator: Daniel Kreisel, 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,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: Earl Schwark, MS    919-681-5775    earl.schwark@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         
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15632
Contact: Diana Zaldonis, MPH, BSN    412-647-8323    zaldonisdb@upmc.edu   
Principal Investigator: Christian Bermudez, MD         
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
Contact: Linda Harrison, RN    206-224-3341    lsh3@uw.edu   
Contact: Michael Mulligan, MD       msmmd@uw.edu   
Principal Investigator: Michael Mulligan, MD         
Sponsors and Collaborators
XVIVO Perfusion
Investigators
Study Director: Mary Pohl, RN, BSN, MPH XVIVO Perfusion, Inc
  More Information

Publications:

Responsible Party: XVIVO Perfusion
ClinicalTrials.gov Identifier: NCT01365429     History of Changes
Other Study ID Numbers: VSS-NA-001, XVO-NA-002
Study First Received: June 2, 2011
Last Updated: March 2, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by XVIVO Perfusion:
Lung Transplant, Transplantation Lung

ClinicalTrials.gov processed this record on July 28, 2015