Steroid Free Immunosuppression or Calcineurin Inhibitor Minimization After Basiliximab Induction Therapy in Kidney Transplantation: Comparison With a Standard Quadruple Immunosuppressive Regimen
Condition: Renal Insufficiency; Kidney Transplantation
MeSH terms: Renal Insufficiency
Study type: Interventional
Phase: Phase 4

Summary: 
      A prospective, open, randomized trial, in which the investigators aim to achieve optimal
      immunosuppression after renal renal transplantation with maximal reduction of side effects,
      especially of vascular injury, chronic allograft nephropathy, osteoporosis and malignancies.
      Immunosuppression without steroids and CNI minimization is compared to standard
      immunosuppression, consisting of tacrolimus OD, mycophenolic acid and corticosteroids.
    

Detailed description: 
      Before transplantation 300 patients will be randomized 1:1:1 in three groups. Group 1 will be
      treated with basiliximab induction and a three day course of steroids followed by a steroid
      free maintenance regimen consisting of standard-dose tacrolimus OD and mycophenolic acid.
      Group 2 will be treated with Basiliximab induction followed by standard-dose tacrolimus OD,
      mycophenolic acid and steroids. Group 3 will be treated with basiliximab induction followed
      by standard-dose tacrolimus OD for six months, whereafter the dose will be reduced plus
      mycophenolic acid and steroids. The total study period will be 2 years. Primary endpoint will
      be renal function, proteinuria and microalbuminuria measured 24 months after transplantation.
      Renal function will be measured by serum Creatinine, Creatinine clearances and CKD-EPI.
      Secondary endpoints will be the degree of tubular atrophy and interstitial fibrosis and the
      degree of arteriolar hyalinosis in renal biopsies taken at 12 and 24 months after
      transplantation. Biopsies will be evaluated according to the Banff Criteria for Renal
      Allograft Biopsy Interpretation. Quantitative morphometric analysis of interstitial fibrous
      tissue will be performed using the digital image analysis technique. Other secondary
      endpoints are patient and graft survival, the incidence of allograft rejection,
      cardiovascular accidents, pulse wave velocity, blood pressure, the number of
      antihypertensives, lipid profile, the incidence of malignancies, the incidence of infectious
      complications, the incidence of post transplant diabetes mellitus and the development of
      osteoporosis.
    

Intervention name(s): tacrolimus OD, mycophenolic acid, prednisolone
Intervention type(s): Drug
Intervention description(s): tacrolimus maintenance 6-10 ng/ml, in the low dose tacrolimus group after 6 months fixed dose reduction of 50% tacrolimus through levels will be 3-5 ng/ml mycophenolic acid 2 dd 720mg, after 2 weeks reduced to 2 dd 540 mg in all groups methylprednisolone 500, 250, 125 mg on day 0, 1, and 2 in all groups prednisolone 1 dd 10 mg, and from week 6 prednisolone 7.5 mg in the standard immunosuppression and low dose tacrolimus group No prednisolone will be given the steroid free group
Other intervention name(s): advagraf, mycophenolic acid
Intervention MeSH terms: Mycophenolic Acid; Prednisolone; Tacrolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: kidney transplantation; immunosuppression; steroids; tacrolimus OD