Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (the 3C Study) - results of a randomized controlled clinical trial.Haynes R, Blackwell L, et al.
American Journal of Transplantation 2017; 11: 11.
This paper reports the results of the sirolimus- versus tacrolimus-based maintenance therapy of the 3C study* which compared mTORi with calcineurin inhibitors in combination with either alemtuzumab- or basiliximab-based induction therapy in kidney transplant recipients.
Participants were randomly assigned to sirolimus-based therapy versus tacrolimus-based therapy.
394 kidney transplant recipients aged ≥18 years with a functioning transplant between 5-7 months after transplantation.
The primary outcome measured was estimated glomerular filtration rate (eGFR) at 18 months after maintenance therapy randomisation. Other measured outcomes included serious adverse events including possible rejection episodes and opportunistic infections, non serious adverse events, site-specific cancer and cause specific mortality and hospitalisations.
This manuscript reports the results of the second randomisation in the UK 3C trial. To recap, de novo kidney transplant recipients were randomised to either alemtuzumab or basiliximab induction, with tacrolimus and myfortic maintenance. At 6 months post-transplant, a second randomisation allocated patients to either continue tacrolimus, or switch to sirolimus. No difference in eGFR was seen between tacrolimus or sirolimus-treated patients at 18 months, and there was an excess of acute rejection in the sirolimus arm (14.7% vs. 3%). There were also more serious infections in sirolimus-treated patients. In all, only 48% participants randomised to sirolimus remained on treatment at the end of the study, with the majority being switched back to tacrolimus. These results provide the strongest evidence yet that routine conversion of stable post-transplant patients to sirolimus is not justified. Whilst the subgroup of patients able to remain on sirolimus did demonstrate improved function, the benefit was small (2.9 ml/min) and given the high probability of adverse events/rejection this cannot be recommended. There are a few small caveats – the study is open label, and less than 50% of those recruited to the initial study underwent the second randomisation, mainly due to clinician preference. This does raise the risk of selection bias, although demographics in those entering/not-entering the second randomisation appear superficially similar.
Previously assessed as *The 3C Study Collaborative Group. Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet. 2014;384(9955):1684-1690.
ClinicalTrials.gov - NCT01120028 and ISRCTN - 88894088