Novartis Everolimus Transition

Phase 4

Completed

Brief Summary: Transition from tacrolimus based triple therapy with Mycophenolate Mofetil (MMF) and steroids in stable renal transplant patients to low intensity tacrolimus, everolimus and prednisone will be associated with improvement in Glomular Filtration Rate (GFR) and allograft fibrosis.

Recruitment & Eligibility

Inclusion Criteria

At least 18 years of age and able to give informed consent.
Received a first or repeat cadaveric (including ECD) or living donor renal transplant.
Patient has stable graft function, defined as no change of greater than 40% of baseline serum creatinine and no acute rejection during the past month.
Currently receiving tacrolimus, mycophenolate mofetil and prednisone as their immunosuppression regimen

Exclusion Criteria

Biopsy proven acute rejection episode that occurred within the past month.
Malignancy within the past 3 years, except for non-melanoma skin cancer.
Currently enrolled in an investigational drug trial.
Woman of child bearing potential not utilizing an effective form of birth control.
Patients with uncontrolled dyslipidemia, defined at serum fasting LDL >200 mg/dL or serum fasting triglycerides >500 mg/dL.
Patients with a spot urine protein to creatinine ratio of > 800 mg of protein per gram of creatinine.
WBC < 2,000 cells/mm3
Platelets < 75,000 cells/mm3
Patients who have received an organ transplant other than a kidney.
Patients with a history of biopsy proven FSGS, MPGN, or PGN.

Arm && Interventions

Group	Intervention	Description
Standard of Care	Standard of Care	Tacrolimus, mycophenolate mofetil and steroids
Low intensity Tacrolimus	Everolimus	Low tacrolimus, everolimus, and steroids

Primary Outcome Measures

Name	Time	Method
Kidney Allograft Fibrosis Assessment	1 year	Measure and compare the change in interstitial fibrosis (morphometric analysis of trichrome stained slides) at one-year post-transplant in patients converted to everolimus, low intensity tacrolimus and prednisone versus the standard of care tacrolimus, mycophenolate and prednisone regimen. The scale is a percentage of the tissue that demonstrates fibrosis. The scale range is 0 to 100%. The higher the percentage, the worse the fibrosis and the poorer the prognosis. A lower score (percentage) is therefore better.

Secondary Outcome Measures

Name	Time	Method
Renal Function Measured by Estimated Glomerular Filtration Rate (eGFR)	1 year	Measure and compare the estimated GFR (using the 4-variable modified MDRD equation) in patients converted to everolimus, low intensity tacrolimus and prednisone versus the standard of care tacrolimus, mycophenolate and prednisone regimen, both at one year and two years post-transplant.
Adverse Drug Reactions	2 year	Measure and compare the incidence of significant immunosuppressant-related adverse drug reactions for each group.
Kidney Allograft Survival	1 year	Compare the patient and graft survival rates at one-year post-transplant in each group.
Percentage of Participants Discontinuing or Modifying Immunosuppressant Use	2 year	Measure and compare the rates of immunosuppressant discontinuation and modification for each group.
Infection	2 year	Compare the rates of post-transplant infections, including CMV, BK, and admissions to the hospital for infectious causes in each group.