24 Months Follow-up, Two Arm Study to Compare the Cardiovascular Profile in a Regimen With Everolimus + Mycophenolic Acid (MPA) Versus (vs.) a Regimen of CNI+MPA in Maintenance Renal Transplant Recipients

Phase 4

Completed

Conditions: Renal Transplant

Interventions: Drug: Tacrolimus
Drug: Everolimus
Drug: Mycophenolic acid (MPA)

Registration Number: NCT01169701

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The objective of the study is to compare the cardiovascular profile of an everolimus and mycophenolic acid immunosuppressive regimen with a calcineurin inhibitor and mycophenolic acid regimen in maintenance renal transplant patients

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 71

Inclusion Criteria

Received kidney transplant > 6 months and < 3 years prior to study enrollment
Receiving immunosuppressive regimen that includes tacrolimus and mycophenolic acid
Between 18 and 70 years of age
Willing to provide written informed consent

Exclusion Criteria

Patients with an actual serum creatinine ≥ 2 mg/dl and/or eGFR≤ 40 ml/min and/or proteinuria≥ 500mg/day
Patients who suffered from severe humoral and/or cellular rejection (≥ BANFF IIb, recurrent acute rejection or steroid resistant acute rejection in the previous years
Patients who have severe hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >8.5 mmol/L). Patients with controlled hyperlipidemia are acceptable.
Diabetic patients
Woman of child-bearing potential who is planning to become pregnant or is pregnant and/or lactating who is unwilling to use effective means of contraception
Presence of psychiatric illness (i.e., schizophrenia, major depression) that, in the opinion of the site investigator, would interfere with study requirements
Any other medical condition that, in the opinion of the site investigator based on recall or chart review would interfere with completing the study
Receiving any investigational drug or have received any investigational drug within 30 days prior to study enrollment

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tacrolimus	Mycophenolic acid (MPA)	Participants continued with the same tacrolimus+Mycophenolic acid (MPA) (Myfortic® or Cell-Cept®) doses that were taken before study initiation (tacrolimus levels 4-7 ng/ml).
Everolimus	Mycophenolic acid (MPA)	Participants received an initial dose (day 1) of Everolimus (EVL) 2mg at night and tacrolimus (if taking Prograf®, a full dose of Prograf® in the morning and a 50% dose of Prograf® at night; if taking Advagraf®, a 75% dose in the morning. On days 2 and 3, participants took EVL 2 mg twice daily (bid) without tacrolimus. On days 4 and 5, the EVL dose was adjusted and levels maintained between 5-8 ng/mL. Participants also continued with their MPA doses that were taken prior to study initiation.
Tacrolimus	Tacrolimus	Participants continued with the same tacrolimus+Mycophenolic acid (MPA) (Myfortic® or Cell-Cept®) doses that were taken before study initiation (tacrolimus levels 4-7 ng/ml).
Everolimus	Tacrolimus	Participants received an initial dose (day 1) of Everolimus (EVL) 2mg at night and tacrolimus (if taking Prograf®, a full dose of Prograf® in the morning and a 50% dose of Prograf® at night; if taking Advagraf®, a 75% dose in the morning. On days 2 and 3, participants took EVL 2 mg twice daily (bid) without tacrolimus. On days 4 and 5, the EVL dose was adjusted and levels maintained between 5-8 ng/mL. Participants also continued with their MPA doses that were taken prior to study initiation.
Everolimus	Everolimus	Participants received an initial dose (day 1) of Everolimus (EVL) 2mg at night and tacrolimus (if taking Prograf®, a full dose of Prograf® in the morning and a 50% dose of Prograf® at night; if taking Advagraf®, a 75% dose in the morning. On days 2 and 3, participants took EVL 2 mg twice daily (bid) without tacrolimus. On days 4 and 5, the EVL dose was adjusted and levels maintained between 5-8 ng/mL. Participants also continued with their MPA doses that were taken prior to study initiation.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Left Ventricular Mass Index (LVMI)	Baseline, Month 24	Left ventricular hypertrophy grade was assessed by echocardiogram where the left ventricular mass index was calculated. The presence of LVM was defined as \> 49.2 g/m\^2.7 in men and \>46.7 g/m\^2.7 in women. A negative change from baseline indicates improvement.

Secondary Outcome Measures

Name	Time	Method
Pulse Wave Velocity (PWV)	Month 6, month 24	Utilizing the SphygmoCor Device, ECG leads placed at the carotid and femoral arteries provided the measure of the pulse wave at that particular arterial location. The distance between the two vascular beds divided by the pulse wave time shift provided a measure of the pulse wave velocity.
Renal Function Measured by Serum Creatinine	Month 6, month 12, month 24	Serum samples were collected to analyze serum creatinine.
Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP)	Baseline, month 6, month 24	Blood samples were collected to analyze Troponin I and collagen type 1 C-telopeptide (ICTP). A negative change from baseline indicates improvement.
Change From Baseline in the Cardiovascular Biomarker, Glycosylated Hemoglobin (HbA1c)	Baseline, month 6, month 24	Blood samples were collected to analyze HbA1c. A negative change from baseline indicates improvement.
Change From Baseline in the Cardiovascular Biomarker, Type 1 Procollagen Amino-terminal-propeptide (PINP)	Baseline, month 6, month 24	Blood samples were collected to analyze PCR. A negative change from baseline indicates improvement.
Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure	Baseline, Month 6, month 12, month 24	Blood pressure was measured using ambulatory blood pressure monitoring (ABPM). A negative change from baseline indicates improvement.
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up	Month 24	The incidence of BPAR, graft loss, death and lost to follow-up events was calculated using relative frequency.
Percentage of Participants With Major Cardiovascular Events (MACE)	Month 24	The percentage of participants who experienced MACE were reported. MACE included acute myocardial infarction, insertion or replacement of implantable defibrillator, peripheral vascular disorders, congestive heart failure, coronary artery bypass, other events, percutaneous coronary intervention and stroke.
Renal Function as Measured by Creatinine Clearance	Month 6, month 12, month 24	Creatinine clearance was calculated using the Cockroft-Gault formula.
Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR)	Month 6, month 12, month 24	Estimated GFR was caluclated using the modification of diet in renal disease (MDRD) formula.
Change From Baseline in the Cardiovascular Biomarker, N-terminal Pro-brain Natriuretic Peptide Fraction (NT-proBNP)	Baseline, month 6, month 24	Blood samples were collected to analyze NT-proBNP. A negative change from baseline indicates improvement.
Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO)	Baseline, month 6, month 24	Blood samples were collected to analyze MPO. A negative change from baseline indicates improvement.
Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP)	Baseline, month 6, month 24	Blood samples were collected to analyze CRP. A negative change from baseline indicates improvement.