Comparison of the Efficacy and Safety of Sirolimus Versus Everolimus Versus Mycophenolate in Kidney Transplantation

Study Overview
=================
Brief Summary
-----------------
This study was designed to compare 3 immunosuppression regimens: sirolimus and tacrolimus versus everolimus and tacrolimus versus mycophenolate and tacrolimus. The primary outcome is the incidence of cytomegalovirus infection / disease, a relevant medical need in the absence of pharmacological prophylaxis.

Official Title
-----------------
Comparison of the Efficacy and Safety of Sirolimus, Everolimus or Mycophenolate in Renal Transplant Recipients Receiving Induction With Anti-thymocyte Globulin, Tacrolimus and Prednisone

Conditions
-----------------
Kidney Transplant Infection

Intervention / Treatment
-----------------
* Drug: Sirolimus
* Drug: Everolimus
* Drug: Mycophenolic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Recipients, adults of the first living or deceased donor kidney transplant; Patients who agreed to participate in the study and signed the informed consent form Exclusion Criteria: Receptors with a medical history of nephrotic syndrome or focal and segmental glomerulosclerosis confirmed as the etiology of end-stage renal disease; Receptors with poor understanding about chronic kidney disease and its treatment alternatives; Receptors with early history of non compliance to treatment with immunosuppressive drugs; Retransplantation; Multi-organ recipients; Recipients with BMI> 30 kg / m2; KDPI> 80%; Cold ischemia time greater than 24 hours; Receptors with a percentage of anti-HLA antibodies above 50%, either class I or Class II; Women of childbearing potential who do not undertake contraceptive methods (condoms or oral contraceptives). Patients receiving immunosuppressive therapy prior to transplantation, except low dose of prednisone; Patients with severe uncontrolled dyslipidemia; Patients who have a known contraindication for administration of any of the immunosuppressive drugs provided for in this study;

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sirolimus +tacrolimus<br>Patients will receive initial dose of 0,05 mg/kg BID oftacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of sirolimus of 3mg once a day to reach blood trough concentration between 4-8 ng/mL. | Drug: Sirolimus<br>* sirolimus combined to reduced dose of tacrolimus<br>* Other names: Rapamune;|
| Experimental: everolimus +tacrolimus<br>Patients will receive initial dose of 0,05 mg/kg BID de tacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of 1.5 mg BID of everolimus to reach blood trough concentration between 4-8 ng/mL. | Drug: Everolimus<br>* everolimus combined to reduced dose of tacrolimus<br>* Other names: Certican;|
| Active Comparator: mycophenolate +tacrolimus<br>Patients will receive initial dose of 0,1 mg/kg BID de tacrolimusto reach blood trough concentration between Fixed dose of mycophenolate (mycophenolate mofetil, 1 g BID or sodium mycophenolate, 720 mg BID). | Drug: Mycophenolic acid<br>* Control arm: mycophenolate combined to regular tacrolimus<br>* Other names: mycophenolate sodium;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Cytomegalovirus Infection or Disease | Incidence of CMV infection/disease in three study groups (SRL, EVR anda MPS). | 12 months follow up |