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Belatacept Pilot Study in Lung Transplantation Immunosuppression in Lung Transplantation

Sponsor
Washington University School of Medicine (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03388008
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH), Bristol-Myers Squibb (Industry)
27
Enrollment
2
Locations
2
Arms
29.4
Anticipated Duration (Months)
13.5
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a pilot randomized controlled trial examining the feasibility of conducting a large scale randomized controlled trial of belatacept-based immunosuppression in lung transplantation. This pilot study will enroll 40 lung transplant recipients and randomize them to belatacept-based immunosuppression or standard of care. The primary endpoint of the study is the development of donor-specific HLA antibodies after transplantation. All study participants will be followed for a minimum of 12 months after transplantation.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Lung transplantation is the ultimate treatment for patients with advanced lung disease. However, long-term outcomes remain disappointing and the median survival after transplantation is approximately 5.5 years. Beyond the first year after transplantation, chronic lung allograft dysfunction is the leading cause of death. The exact mechanisms that lead to chronic lung allograft dysfunction are unclear, but the development of donor-specific HLA antibodies is an independent risk factor. In fact, studies have consistently identified the development of donor-specific HLA antibodies as a significant and independent risk factor for chronic lung allograft dysfunction and mortality after transplantation.

Belatacept is a CTLA4-Ig fusion protein that binds CD80 and CD86 thereby blocking CD28 co-stimulatory signals. Belatacept has been extensively studied in kidney transplantation. In a long-term study, patients treated with Belatacept had better survival than those treated with Cyclosporine. Importantly, Belatacept-treated patients were significantly less likely to develop donor-specific HLA antibodies than Cyclosporine-treated patients. Nonetheless, Belatacept has not been formally evaluated after lung transplantation. The investigators hypothesize that Belatacept-based immunosuppression would result in a lower incidence of donor-specific HLA antibodies and that this would result in better chronic lung allograft dysfunction-free survival after transplantation. Before conducting a large scale randomized controlled trial to test this hypothesis, the investigators plan to conduct the current pilot randomized controlled trial to examine the feasibility of conducting the large scale randomized controlled trial.

The investigators plan to enroll and randomize 40 lung transplant recipients at 2 sites. All recipients will be treated with anti-thymocyte globulin for induction immunosuppression. Those randomized to standard of care immunosuppression will be treated with Tacrolimus, Mycophenolate mofetil, and prednisone. Those randomized to Belatacept-based immunosuppression will be treated with Belatacept, Tacrolimus, and prednisone for the first 89 days; on day 90, Mycophenolate mofetil will be substituted for Tacrolimus and patients will be continued on Belatacept, Mycophenolate mofetil, and prednisone for the remainder of year 1 after transplantation.

Patients in both groups will be monitored closely for episodes of acute cellular rejection, lymphocytic bronchiolitis, and antibody-mediated rejection with surveillance bronchoscopy and transbronchial lung biopsies on days 28, 84, 112, 168, 252, and 365 (± 7 days) as part of the sites' routine clinical protocols. In addition, patients will be monitored for the development of donor-specific HLA antibodies with routine blood tests on on days 10 (± 3 days), 28, 56, 84, 112, 168, 252, and 365 (± 7 days).

The primary endpoint of the study is a composite of the development of donor-specific HLA antibodies, re-transplantation, and death. Secondary endpoints include acute cellular rejection, lymphocytic bronchiolitis, antibody-mediated rejection, chronic lung allograft dysfunction, survival, cytomegalovirus infection, bacterial infection, community-acquired respiratory viral infection, chronic kidney disease stage 3, malignancy, hypertension, diabetes, and hypercholesterolemia.

Study Design

Study Type:
Interventional
Actual Enrollment :
27 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Study participants will be randomized to 1 of 2 arms: Belatacept-based immunosuppression or standard of care immunosuppressionStudy participants will be randomized to 1 of 2 arms: Belatacept-based immunosuppression or standard of care immunosuppression
Masking:
Single (Outcomes Assessor)
Masking Description:
Investigators examining lung biopsy results and blood for the development of donor-specific HLA antibodies will be blinded to study participants' treatment arm assignment.
Primary Purpose:
Treatment
Official Title:
A Pilot Randomized Controlled Trial of De Novo Belatacept-Based Immunosuppression in Lung Transplantation
Actual Study Start Date :
Dec 17, 2019
Actual Primary Completion Date :
Aug 31, 2021
Anticipated Study Completion Date :
May 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Standard of care

Tacrolimus + Mycophenolate mofetil + prednisone from day 0 through day 365

Drug: Tacrolimus
Tacrolimus will be dosed enterally or sublingually within 48 hours of transplantation and the dose will be adjusted to target a trough blood level of 8-15 ng/ml
Other Names:
  • Prograf

    • Drug: ATG
    Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation
    Other Names:
  • Thymoglobulin

    • Drug: Mycophenolate Mofetil
    Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation
    Other Names:
  • Cellcept, Myfortic

    • Drug: Methylprednisolone
    Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses
    Other Names:
  • Solumedrol

    • Drug: Prednisone
    Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365
    Experimental: Belatacept-based immunosuppression

    Belatacept + Tacrolimus + prednisone from day 0 through day 89, then Belatacept + Mycophenolate mofetil + prednisone from day 90 through day 365

    Drug: Belatacept
    Belatacept will be dosed at 10 mg/kg of actual body weight on days 0, 7, 14, 28, 56, and 84 then at 5 mg/kg on day 112 and every 28 days through day 364 (i.e., on days 140, 168, 196, 224, 252, 280, 308, 336, and 364)
    Other Names:
  • Nulojix

    • Drug: ATG
    Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation
    Other Names:
  • Thymoglobulin

    • Drug: Mycophenolate Mofetil
    Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation
    Other Names:
  • Cellcept, Myfortic

    • Drug: Methylprednisolone
    Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses
    Other Names:
  • Solumedrol

    • Drug: Prednisone
    Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365

    Outcome Measures

    Primary Outcome Measures

    1. Donor-specific HLA Antibodies, Re-transplantation, or Death [365 days]

      The Outcome Measure is a composite primary endpoint of the development of donor-specific HLA antibodies, re-transplantation, or death. Testing for donor-specifc HLA antibodies was performed at study-specified time points using the single antigen bead assay at the study core lab. Donor-specific HLA antibodies were defined as reactivity with a mean fluorescence intensity (MFI) ≥ 2,000.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Provided written informed consent for study participation

    • Underwent single or bilateral lung transplantation

    • Negative urine pregnancy test for women of child bearing potential and willingness to use highly-effective contraception

    Exclusion Criteria:

    • Requiring invasive mechanical ventilation immediately before transplantation

    • Requiring extracorporeal life support (ECLS) (i.e., ECMO) immediately before transplantation

    • Received treatment to deplete HLA antibodies before transplantation to improve the possibility of transplantation

    • Having DSA immediately before transplantation (i.e., positive virtual crossmatch)

    • Listed for multi-organ transplant (e.g., heart-lung, liver-lung, kidney-lung)

    • Pregnant or breast-feeding

    • Active infection with Hepatitis B or C virus

    • Active infection with human immunodeficiency virus (HIV)

    • Chronic infection with Burkholderia cepacia complex before transplantation

    • Epstein Barr Virus (EBV) seronegative status

    • Participation in another interventional clinical trial

    • Allograft dysfunction requiring ECMO support after transplantation

    • Delayed chest closure after transplantation

    • Severe coagulopathy and significant bleeding in the opinion of the PI

    • Any condition that in the opinion of the site PI introduces undue risk by participating in this study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine Saint Louis Missouri United States 63110
    2 Houston Methodist Hospital Houston Texas United States 77030

    Sponsors and Collaborators

    • Washington University School of Medicine
    • National Heart, Lung, and Blood Institute (NHLBI)
    • Bristol-Myers Squibb

    Investigators

    • Principal Investigator: Ramsey R Hachem, MD, Washington University School of Medicine

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT03388008
    Other Study ID Numbers:
    • Bela Lung Pilot
    First Posted:
    Jan 2, 2018
    Last Update Posted:
    Nov 30, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Washington University School of Medicine
    donor-specific HLA antibodies
    lung transplantation
    Additional relevant MeSH terms:
    Mycophenolic Acid
    Prednisone
    Methylprednisolone
    Methylprednisolone Hemisuccinate
    Abatacept
    Tacrolimus
    Thymoglobulin

    Study Results

    Participant Flow

    Recruitment Details Participants were recruited at 2 centers (Washington University in St. Louis and Houston Methodist Hospital) between 12/2019 and 5/2021.
    Pre-assignment Detail
    Arm/Group Title Standard of Care Belatacept-based Immunosuppression
    Arm/Group Description Tacrolimus + Mycophenolate mofetil + prednisone from day 0 through day 365 Tacrolimus: Tacrolimus will be dosed enterally or sublingually within 48 hours of transplantation and the dose will be adjusted to target a trough blood level of 8-15 ng/ml ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365 Belatacept + Tacrolimus + prednisone from day 0 through day 89, then Belatacept + Mycophenolate mofetil + prednisone from day 90 through day 365 Belatacept: Belatacept will be dosed at 10 mg/kg of actual body weight on days 0, 7, 14, 28, 56, and 84 then at 5 mg/kg on day 112 and every 28 days through day 364 (i.e., on days 140, 168, 196, 224, 252, 280, 308, 336, and 364) ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365
    Period Title: Overall Study
    STARTED 14 13
    COMPLETED 14 13
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Standard of Care Belatacept-based Immunosuppression Total
    Arm/Group Description Tacrolimus + Mycophenolate mofetil + prednisone from day 0 through day 365 Tacrolimus: Tacrolimus will be dosed enterally or sublingually within 48 hours of transplantation and the dose will be adjusted to target a trough blood level of 8-15 ng/ml ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365 Belatacept + Tacrolimus + prednisone from day 0 through day 89, then Belatacept + Mycophenolate mofetil + prednisone from day 90 through day 365 Belatacept: Belatacept will be dosed at 10 mg/kg of actual body weight on days 0, 7, 14, 28, 56, and 84 then at 5 mg/kg on day 112 and every 28 days through day 364 (i.e., on days 140, 168, 196, 224, 252, 280, 308, 336, and 364) ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365 Total of all reporting groups
    Overall Participants 14 13 27
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    59.5
    (11.8)
    57.8
    (7.5)
    58.7
    (9.8)
    Sex: Female, Male (Count of Participants)
    Female
    5
    35.7%
    4
    30.8%
    9
    33.3%
    Male
    9
    64.3%
    9
    69.2%
    18
    66.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    14.3%
    1
    7.7%
    3
    11.1%
    White
    12
    85.7%
    12
    92.3%
    24
    88.9%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    14
    100%
    13
    100%
    27
    100%
    Diagnosis (Count of Participants)
    Interstitial Lung Disease
    8
    57.1%
    7
    53.8%
    15
    55.6%
    COPD
    0
    0%
    4
    30.8%
    4
    14.8%
    Pulmonary Arterial Hypertension
    2
    14.3%
    0
    0%
    2
    7.4%
    Other
    4
    28.6%
    2
    15.4%
    6
    22.2%
    Operation (Count of Participants)
    Bilateral lung transplant
    11
    78.6%
    12
    92.3%
    23
    85.2%
    Single lung transplant
    3
    21.4%
    1
    7.7%
    4
    14.8%

    Outcome Measures

    1. Primary Outcome
    Title Donor-specific HLA Antibodies, Re-transplantation, or Death
    Description The Outcome Measure is a composite primary endpoint of the development of donor-specific HLA antibodies, re-transplantation, or death. Testing for donor-specifc HLA antibodies was performed at study-specified time points using the single antigen bead assay at the study core lab. Donor-specific HLA antibodies were defined as reactivity with a mean fluorescence intensity (MFI) ≥ 2,000.
    Time Frame 365 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Standard of Care Belatacept-based Immunosuppression
    Arm/Group Description Tacrolimus + Mycophenolate mofetil + prednisone from day 0 through day 365 Tacrolimus: Tacrolimus will be dosed enterally or sublingually within 48 hours of transplantation and the dose will be adjusted to target a trough blood level of 8-15 ng/ml ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365 Belatacept + Tacrolimus + prednisone from day 0 through day 89, then Belatacept + Mycophenolate mofetil + prednisone from day 90 through day 365 Belatacept: Belatacept will be dosed at 10 mg/kg of actual body weight on days 0, 7, 14, 28, 56, and 84 then at 5 mg/kg on day 112 and every 28 days through day 364 (i.e., on days 140, 168, 196, 224, 252, 280, 308, 336, and 364) ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365
    Measure Participants 14 13
    Death
    0
    0%
    5
    38.5%
    Donor-specific HLA antibodies
    3
    21.4%
    3
    23.1%
    Re-transplantation
    0
    0%
    0
    0%

    Adverse Events

    Time Frame Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
    Adverse Event Reporting Description
    Arm/Group Title Standard of Care Belatacept-based Immunosuppression
    Arm/Group Description Tacrolimus + Mycophenolate mofetil + prednisone from day 0 through day 365 Tacrolimus: Tacrolimus will be dosed enterally or sublingually within 48 hours of transplantation and the dose will be adjusted to target a trough blood level of 8-15 ng/ml ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365 Belatacept + Tacrolimus + prednisone from day 0 through day 89, then Belatacept + Mycophenolate mofetil + prednisone from day 90 through day 365 Belatacept: Belatacept will be dosed at 10 mg/kg of actual body weight on days 0, 7, 14, 28, 56, and 84 then at 5 mg/kg on day 112 and every 28 days through day 364 (i.e., on days 140, 168, 196, 224, 252, 280, 308, 336, and 364) ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365
    All Cause Mortality
    Standard of Care Belatacept-based Immunosuppression
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/14 (0%) 5/13 (38.5%)
    Serious Adverse Events
    Standard of Care Belatacept-based Immunosuppression
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/14 (71.4%) 10/13 (76.9%)
    Cardiac disorders
    Atrial fibrillation 2/14 (14.3%) 2 0/13 (0%) 0
    Gastrointestinal disorders
    Nausea and vomiting 0/14 (0%) 0 2/13 (15.4%) 2
    Dysphagia 1/14 (7.1%) 1 0/13 (0%) 0
    Immune system disorders
    Acute rejection 1/14 (7.1%) 1 0/13 (0%) 0
    Infections and infestations
    COVID-19 infection 3/14 (21.4%) 3 2/13 (15.4%) 2
    Surgical site infection 1/14 (7.1%) 1 1/13 (7.7%) 1
    Pneumonia 0/14 (0%) 0 1/13 (7.7%) 2
    Cytomegalovirus infection 1/14 (7.1%) 1 2/13 (15.4%) 2
    Parainfluenza virus infection 1/14 (7.1%) 1 0/13 (0%) 0
    Musculoskeletal and connective tissue disorders
    Multiple fractures 0/14 (0%) 0 1/13 (7.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Post-transplant lymphoproliferative disease 0/14 (0%) 0 1/13 (7.7%) 1
    Nervous system disorders
    Syncope 1/14 (7.1%) 1 0/13 (0%) 0
    Headache 0/14 (0%) 0 1/13 (7.7%) 1
    Renal and urinary disorders
    Acute kidney injury 2/14 (14.3%) 2 0/13 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure 4/14 (28.6%) 4 6/13 (46.2%) 12
    Hemoptysis 0/14 (0%) 0 1/13 (7.7%) 1
    Hemothorax 0/14 (0%) 0 1/13 (7.7%) 1
    Vascular disorders
    Venous Thromboembolism 0/14 (0%) 0 2/13 (15.4%) 2
    Limb ischemia 1/14 (7.1%) 1 0/13 (0%) 0
    Other (Not Including Serious) Adverse Events
    Standard of Care Belatacept-based Immunosuppression
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/14 (85.7%) 13/13 (100%)
    Blood and lymphatic system disorders
    Thrombocytopenia 6/14 (42.9%) 6 5/13 (38.5%) 5
    Anemia 8/14 (57.1%) 8 9/13 (69.2%) 10
    Leukocytosis 1/14 (7.1%) 1 0/13 (0%) 0
    Leukopenia 0/14 (0%) 0 3/13 (23.1%) 3
    Cardiac disorders
    Atrial fibrillation 3/14 (21.4%) 3 6/13 (46.2%) 6
    Arrhythmia 1/14 (7.1%) 1 0/13 (0%) 0
    Cardiac dysfunction 1/14 (7.1%) 1 1/13 (7.7%) 1
    Tachycardia 0/14 (0%) 0 2/13 (15.4%) 2
    Endocrine disorders
    Hyperglycemia 2/14 (14.3%) 2 1/13 (7.7%) 1
    Hypercholesterolemia 0/14 (0%) 0 1/13 (7.7%) 1
    Eye disorders
    Cataract 1/14 (7.1%) 1 0/13 (0%) 0
    Gastrointestinal disorders
    Nausea 4/14 (28.6%) 4 4/13 (30.8%) 4
    Diarrhea 1/14 (7.1%) 1 2/13 (15.4%) 2
    Anorexia 1/14 (7.1%) 1 0/13 (0%) 0
    Gastric distention 1/14 (7.1%) 1 3/13 (23.1%) 3
    Gastroparesis 0/14 (0%) 0 1/13 (7.7%) 1
    GERD 0/14 (0%) 0 1/13 (7.7%) 1
    General disorders
    Hoarseness 1/14 (7.1%) 1 0/13 (0%) 0
    Vocal cord dysfunction 2/14 (14.3%) 2 0/13 (0%) 0
    Dysphonia 0/14 (0%) 0 1/13 (7.7%) 1
    Fever 0/14 (0%) 0 1/13 (7.7%) 1
    Immune system disorders
    Acute cellular rejection 7/14 (50%) 7 3/13 (23.1%) 4
    Hypogammaglobulinemia 0/14 (0%) 0 1/13 (7.7%) 1
    Infections and infestations
    Positive bronchoscopy culture 9/14 (64.3%) 31 8/13 (61.5%) 13
    Upper respiratory infection 1/14 (7.1%) 1 2/13 (15.4%) 4
    Oral candidiasis 0/14 (0%) 0 1/13 (7.7%) 1
    Pneumonia 0/14 (0%) 0 1/13 (7.7%) 1
    Mucocutaneous HSV 0/14 (0%) 0 1/13 (7.7%) 1
    Viral infection 0/14 (0%) 0 1/13 (7.7%) 1
    Urinary tract infection 0/14 (0%) 0 1/13 (7.7%) 1
    Metabolism and nutrition disorders
    Lactic acidosis 1/14 (7.1%) 1 0/13 (0%) 0
    Musculoskeletal and connective tissue disorders
    Generalized weakness 1/14 (7.1%) 1 1/13 (7.7%) 1
    Joint pain 1/14 (7.1%) 1 2/13 (15.4%) 2
    Back pain 0/14 (0%) 0 1/13 (7.7%) 1
    Calf pain 0/14 (0%) 0 1/13 (7.7%) 1
    Nervous system disorders
    Delirium 2/14 (14.3%) 2 3/13 (23.1%) 3
    Gait abnormality 1/14 (7.1%) 1 0/13 (0%) 0
    Tremor 1/14 (7.1%) 1 1/13 (7.7%) 1
    Headache 1/14 (7.1%) 1 1/13 (7.7%) 1
    Psychiatric disorders
    Anxiety 0/14 (0%) 0 1/13 (7.7%) 1
    Renal and urinary disorders
    Electrolyte abnormality 7/14 (50%) 7 5/13 (38.5%) 6
    Acute kidney injury 0/14 (0%) 0 4/13 (30.8%) 4
    Respiratory, thoracic and mediastinal disorders
    Ischemic mucosal airway injury 5/14 (35.7%) 5 4/13 (30.8%) 4
    Pulmonary nodule 1/14 (7.1%) 1 1/13 (7.7%) 1
    Bronchitis 1/14 (7.1%) 1 0/13 (0%) 0
    Bronchomalacia 1/14 (7.1%) 1 0/13 (0%) 0
    Cough 1/14 (7.1%) 1 1/13 (7.7%) 2
    Bronchostenosis 1/14 (7.1%) 1 0/13 (0%) 0
    Pneumothorax 1/14 (7.1%) 1 0/13 (0%) 0
    Diaphragmatic dysfunction 1/14 (7.1%) 1 0/13 (0%) 0
    Pleural effusion 0/14 (0%) 0 5/13 (38.5%) 5
    Anastomotic air leak 0/14 (0%) 0 1/13 (7.7%) 1
    Pulmonary embolism 0/14 (0%) 0 3/13 (23.1%) 3
    Atelectasis 0/14 (0%) 0 3/13 (23.1%) 3
    Pulmonary eosinophilia 0/14 (0%) 0 1/13 (7.7%) 1
    Hemothorax 0/14 (0%) 0 1/13 (7.7%) 1
    Skin and subcutaneous tissue disorders
    Calcific panniculitis 0/14 (0%) 0 1/13 (7.7%) 1
    Wound dehiscence 0/14 (0%) 0 1/13 (7.7%) 1
    Vascular disorders
    Hypotension 3/14 (21.4%) 3 2/13 (15.4%) 2
    Hypovolemia 1/14 (7.1%) 1 0/13 (0%) 0
    Aortic root dilation 1/14 (7.1%) 1 0/13 (0%) 0
    Hypertension 0/14 (0%) 0 1/13 (7.7%) 1
    Orthostasis 0/14 (0%) 0 1/13 (7.7%) 1
    Deep venous thrombosis 1/14 (7.1%) 1 0/13 (0%) 0
    Edema 2/14 (14.3%) 2 0/13 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Ramsey Hachem, MD
    Organization Washington University in St. Louis
    Phone (314) 454-7953
    Email Rhachem@wustl.edu
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT03388008
    Other Study ID Numbers:
    • Bela Lung Pilot
    First Posted:
    Jan 2, 2018
    Last Update Posted:
    Nov 30, 2021
    Last Verified:
    Nov 1, 2021