A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved..
BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.
METHODS: We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1.
RESULTS: After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups.
CONCLUSIONS: We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:108 |
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| Enthalten in: |
Transplantation - 108(2024), 3 vom: 01. März, Seite 777-786 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Howard J [VerfasserIn] |
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| Links: |
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| Themen: |
7D0YB67S97 |
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| Anmerkungen: |
Date Completed 23.02.2024 Date Revised 09.03.2024 published: Print-Electronic ClinicalTrials.gov: NCT03388008 Citation Status MEDLINE |
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| doi: |
10.1097/TP.0000000000004841 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a ClinicalTrials.gov: NCT03388008 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD | ||
| 520 | |a METHODS: We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1 | ||
| 520 | |a RESULTS: After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups | ||
| 520 | |a CONCLUSIONS: We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation | ||
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