RCT Comparing Immunosuppressive Regimens in Elderly Renal Transplant Recipients

In this study two immunosuppressive regimes will be tested; In both groups basiliximab induction will be applied. Additionally, the standard therapy consisting of prednisolone, mycophenolic acid and tacrolimus once-daily (Envarsus®), or the comparator in which mycophenolic acid will be replaced by everolimus combined with strongly reduced levels of tacrolimus once-daily (Envarsus®). When not tolerated,tacrolimus may be replaced by ciclosporin. The hypothesis is that reduced calcineurin inhibitor (CNI) exposure in combination with everolimus will lead to improved allograft function, a reduced incidence of complications and improved quality of life.

This study will consist of two strata: Stratum A: Elderly recipients (≥65 years) of kidneys from elderly deceased donors (≥65 years) within the Eurotransplant Senior Program. Stratum B: Elderly recipients (≥65 years) of kidneys from living donors (all ages) or deceased donors (<65 years). The primary endpoint will be "successful transplantation" which is defined as survival with a functioning allograft with a minimum estimated GFR of 30 ml/min per 1.73 m2 in stratum A and 45 ml/min per 1.73 m2 in stratum B, after 2 years.

The study will be performed by the Dutch transplant centers and the Dutch Kidney Patient Organization (NVN) will participate.

Inclusion criteria

• Written informed consent must be obtained before any assessment is performed
• Male or female subject ≥65 years old
• Subject randomized within 24 hours of completion of transplant surgery
• Stratum A: Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased donor aged 65 years or older
• Stratum B: Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased donor aged below 65 years or a living donor of any age

Exclusion criteria

Exclusion criteria for both stratum A and B

• Subject is a multi-organ transplant recipient
• Recipient of bloodgroup ABO incompatible allograft or CDC cross-match positive transplant
• Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity
• Recipient of a kidney with a cold ischaemia time (CIT) >24 hr
• Recipients of a kidney from an HLA-identical related living donor
• Known intolerability for one or more of the study drugs
• Subject who is HIV positive
• HBsAg and/or a HCV positive subject with evidence of elevated liver function tests (ALT/AST levels ≥2.5 times ULN). Viral serology results obtained within 6 months prior to randomization are acceptable
• Recipient of a kidney from a donor who tests positive for human immunodeficiency virus, (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV)
• Subject with severe systemic infections, current or within the two weeks prior to randomization
• Subject with severe restrictive or obstructive pulmonary disorders
• Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled
• Subject with white blood cell (WBC) count ≤ 2,000/mm3 or with platelet count ≤ 50,000/mm3