Rationale and design of the TACMONO-XL trial; a randomized trial of tacrolimus monotherapy compared to standard triple immune suppressive medication in elderly recipients of a kidney transplant to reduce infection-related mortality and improve quality of life

The number of elderly recipients of a kidney transplant is increasing and now 40% of all kidney recipients in the Netherlands are above 60 years of age at time of transplantation. These recipients are more prone to infections and malignancy and death with a functioning graft is the major cause of graft loss. On the other hand, the incidence of rejection and rejection-related graft loss is substantially lower in elderly recipients. Therefore, lowering immune suppression in this population is a rational approach to finding a better balance between prevention of rejection and side effects. As the rejection incidence sharply decreases after the first months of transplantation, we hypothesize that reduction of immunosuppressive medication after 3 months leading to tacrolimus monotherapy in one year will lead to less infections and better patient survival in KTRs aged 60 years and older, compared to standard immunosuppression. This open label, randomized, multicenter clinical trial will randomize 306 elderly kidney transplant recipients (≥ 60 years) 3 months after kidney transplantation. All recipients will receive basiliximab induction therapy followed by tacrolimus, mycophenolate mofetil and prednisone maintenance. The major criteria for randomization are an eGFR ≥ 25 ml/min per 1.73 m 2 and no prior T cell depletion or antibody-mediated rejection. Recipients are randomized to continuation of the triple immune suppressive regimen or phasing out of prednisone between 3 and 6 months followed by mycophenolate mofetil until tacrolimus monotherapy at 12 months. The primary endpoints are infection-related death and infectious burden while important secondary endpoints are graft and patient survival, rejection-free survival, and quality of life. Follow-up will end at 3 years after transplantation. The TACMONO-XL trial will show whether tacrolimus monotherapy as long-term maintenance therapy after kidney transplantation in the elderly will result in less infections and infection-related death without an increase in rejection incidence while improving quality of life. EU trial number : 2024-517709-10-00, registered June 6th, 2025.