A pilot randomized controlled trial of de novo belatacept-based immunosuppression following anti-thymocyte globulin induction in lung transplantation
The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a two-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial. Twenty-seven participants were randomized to Control (Tacrolimus, Mycophenolate Mofetil, and prednisone, n = 14) or Belatacept-based immunosuppression (Tacrolimus, Belatacept, and prednisone until day 89 followed by Belatacept, Mycophenolate Mofetil, and prednisone, n = 13). All participants were treated with rabbit anti-thymocyte globulin for induction immunosuppression. We permanently stopped randomization and treatment with Belatacept after three participants in the Belatacept arm died compared to none in the Control arm. Subsequently, two additional participants in the Belatacept arm died for a total of five deaths compared to none in the Control arm (log rank p = .016). We did not detect a significant difference in DSA development, acute cellular rejection, or infection between the two groups. We conclude that the investigational regimen used in this study is associated with increased mortality after lung transplantation.
Reviewer: | Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford |
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Conclusion: | This pilot RCT investigated the use of belatacept-based immunosuppression in lung transplant recipients. Standard immunosuppression with Tac/MMF/Pred was compared to belatacept and prednisolone-based immunosuppression in conjunction with tacrolimus for the first 3 months and MMF thereafter. Recruitment was stopped after 3 deaths in the belatacept arm – a further two patients subsequently died. The authors conclude that belatacept-based immunosuppression in lung transplant recipients is associated with excess mortality. The results in such a small number of patients are difficult to interpret – causes of death were different for all 5 recipients (PE, haemothorax, restrictive allograft syndrome, COVID-19 and PTLD). Three deaths related to possible viral infection, which may reflect the overall immunosuppressive burden of the regimen. Given the excess mortality, the DSMB were correct to stop the trial despite the small sample size. |
Jadad score | 2 |
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Allocation concealment | NO |
Data analysis | PER PROTOCOL |
Aims: | This pilot randomised controlled trial (RCT) aimed to examine the efficacy and safety of belatacept-based immunosuppression following lung transplantation. |
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Interventions: | Patients were randomised into two arms: the belatacept- based immunosuppression arm, in which patients received tacrolimus, belatacept, and prednisone until day 89 followed by belatacept, mycophenolate mofetil (MMF), and prednisone; or the control arm, where patients received tacrolimus, MMF and prednisone. |
Participants: | 27 lung transplant recipients. |
Outcomes: | The primary outcome was the feasibility metric of randomising 80% of eligible patients within 4 hours posttransplantation. |
Follow Up: | 365 days |
Funding: | Industry funding and Non-industry funding |
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Publication type: | Randomized Controlled Trial, Randomised Controlled Trial |
Trial registration: | ClinicalTrials.gov - NCT03388008 |
Organ: | Lung |
Language: | English |
Author email: | rhachem@wustl.edu |
MeSH terms: | Abatacept; Antilymphocyte Serum; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Lung Transplantation; Mycophenolic Acid; Pilot Projects; Prednisone; Tacrolimus; 0 (Antilymphocyte Serum); 0 (Immunosuppressive Agents); 7D0YB67S97 (Abatacept); HU9DX48N0T (Mycophenolic Acid); VB0R961HZT (Prednisone); WM0HAQ4WNM (Tacrolimus) |