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

Renal Transplant Clinical Trial

— EVITA  

Official title:

Multicenter, Open-label, Randomized, 24 Months Follow-up, Two Arm Study to Compare the Efficacy of Everolimus in Improving the Cardiovascular Profile in a Regimen With Mycophenolic Acid vs. a Regimen of CNI+MPA in Maintenance Renal Transplant Recipients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01169701
• Other study ID #: CRAD001AES07
• Secondary ID: 2009-013780-19
• Status: Completed
• Phase: Phase 4
• First received: July 22, 2010
• Last updated: November 6, 2015
• Start date: August 2010
• Est. completion date: March 2014

Study information

• Verified date: November 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Transplant

Intervention

Drug:
• Everolimus
Everolimus was supplied in boxes with 60 tablets. Available tablets: 1.0 mg, 0.5 mg and 0.25 mg.
• Tacrolimus
Tacrolimus was administrated as Prograf® or Advagraf®, but could not be changed during study.
• Mycophenolic acid (MPA)
Myfortic® (MFS) was given as 720-1440 mg/day or 360-1440 mg/day. Cell-Cept® (MMF) was given as 1000-2000 mg/day or 500-2000 mg/day.

Locations

Country	Name	City	State
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Left Ventricular Mass Index (LVMI)	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.	Baseline, Month 24	No
Secondary	Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure	Blood pressure was measured using ambulatory blood pressure monitoring (ABPM). A negative change from baseline indicates improvement.	Baseline, Month 6, month 12, month 24	No
Secondary	Pulse Wave Velocity (PWV)	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.	Month 6, month 24	No
Secondary	Percentage of Participants With Major Cardiovascular Events (MACE)	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.	Month 24	Yes
Secondary	Renal Function Measured by Serum Creatinine	Serum samples were collected to analyze serum creatinine.	Month 6, month 12, month 24	No
Secondary	Renal Function as Measured by Creatinine Clearance	Creatinine clearance was calculated using the Cockroft-Gault formula.	Month 6, month 12, month 24	No
Secondary	Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR)	Estimated GFR was caluclated using the modification of diet in renal disease (MDRD) formula.	Month 6, month 12, month 24	Yes
Secondary	Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP)	Blood samples were collected to analyze Troponin I and collagen type 1 C-telopeptide (ICTP). A negative change from baseline indicates improvement.	Baseline, month 6, month 24	No
Secondary	Change From Baseline in the Cardiovascular Biomarker, Glycosylated Hemoglobin (HbA1c)	Blood samples were collected to analyze HbA1c. A negative change from baseline indicates improvement.	Baseline, month 6, month 24	No
Secondary	Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO)	Blood samples were collected to analyze MPO. A negative change from baseline indicates improvement.	Baseline, month 6, month 24	No
Secondary	Change From Baseline in the Cardiovascular Biomarker, N-terminal Pro-brain Natriuretic Peptide Fraction (NT-proBNP)	Blood samples were collected to analyze NT-proBNP. A negative change from baseline indicates improvement.	Baseline, month 6, month 24	No
Secondary	Change From Baseline in the Cardiovascular Biomarker, Type 1 Procollagen Amino-terminal-propeptide (PINP)	Blood samples were collected to analyze PCR. A negative change from baseline indicates improvement.	Baseline, month 6, month 24	No
Secondary	Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP)	Blood samples were collected to analyze CRP. A negative change from baseline indicates improvement.	Baseline, month 6, month 24	No
Secondary	Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up	The incidence of BPAR, graft loss, death and lost to follow-up events was calculated using relative frequency.	Month 24	No