Long-term follow-up of a phase III clinical trial comparing tacrolimus extended-release/MMF, tacrolimus/MMF, and cyclosporine/MMF in de novo kidney transplant recipients.
Silva HT, Yang HC, Meier-Kriesche HU, et al.Transplantation 2014; 97(6): 636-641
Aims
To compare the safety and efficacy of tacrolimus extended-release, tacrolimus, and cyclosporine in a four year long term trial, in de novo kidney transplant recipients.
Interventions
All participants received basiliximab, mycophenolate mofetil and corticosteroids, in addition to tacrolimus extended release (Astagraf XL) once daily, tacrolimus (Prograf) twice daily, or cyclosporine (CsA) twice daily.
Participants
668 de novo kidney transplant recipients.
Outcomes
The study outcomes included patient and graft survival, renal function and development of new-onset diabetes after transplantation.
Follow-up
4 years.
CET Conclusions
This is a long term follow up of a three armed randomised trial comparing Astagraf XL, Prograf and CSA Neoral. Patient and graft survival was not significantly different in the three arms, although there was a trend for better survival in the two tacrolimus arms. Renal function was better in the Astagraf arm than the Prograf or Neoral arms at 4 years, while the incidence of New Onset Diabetes (NODAT) was very much higher in the tacrolimus arms than the Neoral arm, around 40% in the tacrolimus arms at 4 years compared to approximately 20% in the Neoral arm. One confounding effect in this study is that Astagraf XL was supplied by the sponsors for the duration of the study, whereas Prograf and CSA Neoral were only provided for the first year of the study and is perhaps the reason that withdrawals were much higher in the latter two arms. Nevertheless the efficacy of the Astagraf XL was certainly not inferior to Prograf and the only downside was the incidence of NODAT, which was higher in the Atragraf XL arm than the Prograf arm.
Data analysis
Modified intention-to-treat analysis
Quality notes
Previously assessed in Silva HT, Yang HC, Abouljoud M, et al. One-year results with extended release tacrolimus/MMF, tacrolimus/MMF and cyclosporine/MMF in de novo kidney transplant recipients. Am J Transplant 2007; 7: 595
Trial registration
Not reported