Steroid Free Immunosuppression or Calcineurin Inhibitor Minimization After Basiliximab Induction Therapy in Kidney Transplantation: Comparison With a Standard Quadruple Immunosuppressive Regimen
- Conditions
- Renal InsufficiencyKidney Transplantation
- Interventions
- Registration Number
- NCT01560572
- Lead Sponsor
- University Medical Center Groningen
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 305
- recipient of a kidney graft (first of second) from a deceased or living (non-HLA identical) donor
- patients with multi-organ transplants
- patients who are receiving a third or fourth transplant
- patients who have > 75% (current of historic) panel reactive antibodies
- patients receiving a kidney from a HLA identical living donr
- female patients who are pregnant or unwilling to used adequate contraception during the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description standard immunosuupression tacrolimus OD, mycophenolic acid, prednisolone triple maintenance immunosuppression with tacrolimus OD (maintenance 6-10 ng/ml), mycophenolic acid 2 dd 540mg and prednisolone 7.5 mg steroidfree tacrolimus OD, mycophenolic acid, prednisolone maintenance immunosuppression with tacrolimus OD (target range 6-10 ng/ml), mycophenolic acid (2 dd 540 mg) low dose tacrolimus tacrolimus OD, mycophenolic acid, prednisolone triple maintenance immunosuppression with tacrolimus OD (maintenance 6-10 ng/ml), mycophenolic acid 2 dd 540mg and prednisolone 7.5 mg. After 6 months lowering of tacrolimus OD maintenance 3-5 ng/ml
- Primary Outcome Measures
Name Time Method renal function parameters 24 months renal function as measured by serum Creatinine and Creatinine Clearance, CKD-EPI, proteinuria
- Secondary Outcome Measures
Name Time Method rejection episodes two years number of treated biopsy proven acute rejection episodes (as scored by pathologist via Banff classification)
graft and patient survival two years graft and patient survival
myocardial infarctions two years number of myocardial infarctions
tubular atrophy and interstitial fibrosis 24 months tubular atrophy and interstitial fibrosis in renal biopsies
cerebrovascular accidents two years number of cerebrovascular accidents
number of participants with osteoporosis 2 years as established by dexa bone densitometry
number of participants with infectious complications two years bacterial and viral infections as measured by culture (bacterial infections) or PCR (viral infections)
Trial Locations
- Locations (3)
Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands