Novartis Everolimus Transition

Study Overview
=================
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.

Official Title
-----------------
Safety and Efficacy of Everolimus Transition in Minimizing Progressive Graft Dysfunction and Interstitial Fibrosis in Adult Kidney Transplant Recipients

Conditions
-----------------
Graft Dysfunction, Interstitial Fibrosis

Intervention / Treatment
-----------------
* Drug: Everolimus
* Other: Standard of Care


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low intensity Tacrolimus<br>Low tacrolimus, everolimus, and steroids | Drug: Everolimus<br>* Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus<br>|
| Other: Standard of Care<br>Tacrolimus, mycophenolate mofetil and steroids | Other: Standard of Care<br>* Tacrolimus, mycophenolate mofetil and steroids<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney Allograft Fibrosis Assessment | 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. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function Measured by Estimated Glomerular Filtration Rate (eGFR) | 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. | 1 year | 
| Kidney Allograft Survival | Compare the patient and graft survival rates at one-year post-transplant in each group. | 1 year | 
| Percentage of Participants Discontinuing or Modifying Immunosuppressant Use | Measure and compare the rates of immunosuppressant discontinuation and modification for each group. | 2 year | 
| Adverse Drug Reactions | Measure and compare the incidence of significant immunosuppressant-related adverse drug reactions for each group. | 2 year | 
| Infection | Compare the rates of post-transplant infections, including CMV, BK, and admissions to the hospital for infectious causes in each group. | 2 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Everolimus, Graft dysfunction, Interstitial fibrosis