| Autor: |
Alexandre Loupy, Olivier Aubert, Gillian Divard, Christophe Legendre, Julio Pascual, Claudia Sommerer, Federico Oppenheimer, Franco Citterio, Helio Tedesco, Steve Chadban, Mitchell Henry, Flavio Vincenti, Titte Srinivas, Yoshihiko Watarai, Peter Bernhardt |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
BMJ Open, Vol 11, Iss 10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2044-6055 |
| DOI: |
10.1136/bmjopen-2021-052138 |
| Popis: |
Objectives Development of pharmaceutical agents in transplantation is currently limited by long waits for hard endpoints. We applied a validated integrative risk-prognostication system integrative Box (iBox) as a surrogate endpoint to the TRANSFORM Study, a large randomised controlled trial, to project individual patient long-term kidney allograft survival from 1 year to 11 years after randomisation.Design Post-hoc analysis of a randomised open-label controlled trial.Setting Multicentre study including 186 centres in 42 countries worldwide.Participants 2037 de novo kidney transplant recipients.Intervention Participants were randomised (1:1) to receive everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) or mycophenolic acid with standard-exposure CNI (MPA+sCNI).Primary outcome measure The iBox scores were computed for each participant at 1 year after randomisation using functional, immunological and histological parameters. Individual long-term death-censored allograft survival over 4, 6 and 11 years after randomisation was projected with the iBox risk-prognostication system.Results Overall, 940 patients receiving EVR+rCNI and 932 receiving MPA+sCNI completed the 1-year visit. iBox scores generated at 1 year yielded graft survival prediction rates of 90.9% vs 92.1%, 87.9% vs 89.5%, and 80.0% vs 82.4% in the EVR+rCNI versus MPA+sCNI arms at 4, 6, and 11 years post-randomisation, respectively (all differences below the 10% non-inferiority margin defined by study protocol). Inclusion of immunological and histological Banff diagnoses parameters in iBox scores resulted in comparable and non-inferior predicted graft survival for both treatments.Conclusions This proof-of-concept study provides the first application of a validated prognostication system as a surrogate endpoint in the field of transplantation. The iBox system, by projecting kidney allograft survival up to 11 years post-randomisation, confirms the non-inferiority of EVR+rCNI versus MPA+sCNI regimen. Given the current process engaged for surrogate endpoints qualification, this study illustrates the potential to fast track development of pharmaceutical agents.Trial registration number TRANSFORM trial: NCT01950819.iBox prognostication system: NCT03474003. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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