Comparison of Sirolimus to Tacrolimus for Long Term Therapy in Kidney Transplant With no Steroids
Condition: Kidney Diseases
MeSH terms: Kidney Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      Kidney transplant patients will be treated with Thymoglobulin (5 days), tacrolimus (Prograf),
      and mycophenolate mofetil (Cellcept) from the time of transplant. They will only receive
      steroids for 4 days and no prednisone after that. At 1 month, they will have a kidney biopsy
      and if it is ok, patients will be treated long term with either continued
      tacrolimus/mycophenolate mofetil or be switched to sirolimus (Rapamune)/mycophenolate
      mofetil. This will be done randomly in a manner similar to flipping a coin. The investigators
      are trying to determine if after the initial therapy patients can stay off steroids long term
      and get better kidney function if they are treated with sirolimus compared to tacrolimus.
      Patients will be followed for 3 years and will repeat kidney biopsies at 1 and 2 years after
      transplant.
    

Detailed description: 
      Abstract:

      Corticosteroids have been a mainstay of immunosuppression for kidney transplantation, but
      they are associated with significant toxicity after long-term use. Recent studies have
      concluded that steroid avoidance is safe and effective when combined with modern
      immunosuppressive maintenance therapy in low risk kidney transplant recipients. These studies
      have included antilymphocyte induction therapy with either an anti IL-2 receptor antibody, or
      an antithymocyte globulin, such as rabbit polyclonal antithymocyte globulin (Thymoglobulin).
      Mayo Clinic Scottsdale has adopted Thymoglobulin induction, tacrolimus, and mycophenolate
      mofetil with rapid steroid taper as their standard immunosuppressive therapy in low risk
      patients. Mayo Clinic Jacksonville is also utilizing this protocol. Together, both sites have
      utilized this approach in 64 patients. Recent improvements in immunosuppressive regimens have
      decreased acute rejection in kidney transplant recipients and increased one-year graft
      survival to nearly 90%. However, long-term graft survival has changed little with 30% of
      grafts being lost to ''chronic allograft nephropathy'' (CAN) in the first five years after
      transplantation. A recent paper highlighted this dilemma and demonstrated that a major cause
      of late CAN was chronic exposure to the nephrotoxic effects of calcineurin inhibitors (CNI)
      tacrolimus and cyclosporine and possibly cytomegalovirus infection. In this study, we will
      focus on the role of CNI in CAN. We propose a prospective, randomized, non-blinded trial of
      Thymoglobulin induction with rapid steroid elimination accompanied by tacrolimus (TAC) and
      mycophenolate mofetil (MMF) maintenance therapy. Patients are to be randomized at 1 month
      post-operatively to either remain on TAC/MMF or switch to SRL/MMF. The primary endpoint will
      be renal function at 1-year post-transplant. Secondary endpoints will include renal function
      at 2 years post-transplant, histology seen on protocol biopsies at 1 and 2 years
      post-transplant, incidence of biopsy proven rejection at 12 months, patient survival, graft
      survival, proportion of patients steroid free at 12 months, infectious complications, bone
      mineral density analysis, incidence of hyperlipidemia, and the incidence of new onset
      post-transplant diabetes mellitus.
    

Intervention name(s): Sirolimus
Intervention type(s): Drug
Intervention description(s): 10 mg oral loading dose followed by 5 mg/day. Measure Sirolimus level weekly and adjust to level of 10-15 ng/ml.
Intervention MeSH terms: Sirolimus
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Kidney Transplantation