Transplant Trial Watch

Early conversion to prednisolone/everolimus as an alternative weaning regimen associates with beneficial renal transplant histology and function: the randomized-controlled MECANO trial.

Bemelman FJ, de Fijter JW, et al.

American Journal of Transplantation 2016 [record in progress].


Aims
To determine whether minimizing exposure to calcineurin inhibitors and total amount of immunosuppression by switching to a non-nephrotoxic double drug regimen early after transplantation would maintain efficacy in renal transplant recipients.

Interventions
Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS) and CsA. At 6 months, patients without rejection were randomized to receive one of three treatment arms; P/CsA, P/MPS, or P/everolimus.

Participants
224 patients aged 18-70 years receiving a first or second renal transplant from a deceased or living donor.

Outcomes
The primary measured outcome was the development of interstitial fibrosis at the 24-month protocol biopsy. Secondary outcomes included the estimated glomerular filtration rate, incidence of acute rejection, and drug-related adverse events.

Follow-up
24 months

CET Conclusions
This report details a well conducted randomised controlled trial. Renal transplant recipients were randomised to conversion from maintenance immune suppression to either prednisolone and cyclosporine or prednisolone and everolimus. There was also a third arm (prednisolone and mycophenolate) that was terminated early due to poor results. At 24 months a protocol biopsy was taken and these showed significantly less fibrosis with everolimus than cyclosporine. Everolimus also showed a better renal function with about 5ml/min better eGFR over several months than cyclosporine. There was no significant difference in rates of clinical rejection over the same time period, development of DSA, patient or graft survival. Importantly there were significantly more serious adverse events with everolimus than cyclosporine, with much higher rates of change in regimen and cardiovascular events. This is of concern given the proven increased risk of hypercholesterolaemia with everolimus.

Jadad score
3

Data analysis
Strict intention-to-treat analysis

Allocation concealment
Yes

Quality notes
Previously assessed as Bemelman FJ, et al. Minimization of maintenance immunosuppression early after renal transplantation: An interim analysis. Transplantation 2009; 88: 421–428.

Trial registration
Netherlands Trial Registry - NTR1615

Funding source
Industry funded