Application of the iBox prognostication system as a surrogate endpoint in the TRANSFORM randomised controlled trial: proof-of-concept study
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 proj...
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| Hauptverfasser: | , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
7 October 2021
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| In: |
BMJ open
Year: 2021, Jahrgang: 11, Heft: 10, Pages: 1-8 |
| ISSN: | 2044-6055 |
| DOI: | 10.1136/bmjopen-2021-052138 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1136/bmjopen-2021-052138 Verlag, kostenfrei, Volltext: https://bmjopen.bmj.com/content/11/10/e052138 
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| Verfasserangaben: | Olivier Aubert, Gillian Divard, Julio Pascual, Federico Oppenheimer, Claudia Sommerer, Franco Citterio, Helio Tedesco, Steve Chadban, Mitchell Henry, Flavio Vincenti, Titte Srinivas, Yoshihiko Watarai, Christophe Legendre, Peter Bernhardt, Alexandre Loupy |
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| 245 | 1 | 0 | |a Application of the iBox prognostication system as a surrogate endpoint in the TRANSFORM randomised controlled trial |b proof-of-concept study |c Olivier Aubert, Gillian Divard, Julio Pascual, Federico Oppenheimer, Claudia Sommerer, Franco Citterio, Helio Tedesco, Steve Chadban, Mitchell Henry, Flavio Vincenti, Titte Srinivas, Yoshihiko Watarai, Christophe Legendre, Peter Bernhardt, Alexandre Loupy |
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| 520 | |a 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. | ||
| 650 | 4 | |a clinical trials | |
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| 650 | 4 | |a statistics & research methods | |
| 650 | 4 | |a transplant medicine | |
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| 700 | 1 | |a Pascual, Julio |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Loupy, Alexandre |e VerfasserIn |4 aut | |
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