A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation.
التاريخ
2024-03-01المؤلف
Huang, Howard JSchechtman, Kenneth
Askar, Medhat
Bernadt, Cory
Mitter, Brigitte
Dore, Peter
Goodarzi, Ahmad
Yau, Simon
Youssef, J Georges
Witt, Chad A
Byers, Derek E
Vazquez-Guillamet, Rodrigo
Halverson, Laura
Nava, Ruben
Puri, Varun
Kreisel, Daniel
Gelman, Andrew E
Hachem, Ramsey R
...show more authors ...show less authors
البيانات الوصفية
عرض كامل للتسجيلةالملخص
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. 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. 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. We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.
المجموعات
- أبحاث الطب [1418 items ]