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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 (EVITA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01169701
First received: July 22, 2010
Last updated: November 6, 2015
Last verified: November 2015
  Purpose
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

Condition Intervention Phase
Renal Transplant
Drug: Everolimus
Drug: Tacrolimus
Drug: Mycophenolic acid (MPA)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Left Ventricular Mass Index (LVMI) [ Time Frame: Baseline, Month 24 ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure [ Time Frame: Baseline, Month 6, month 12, month 24 ] [ Designated as safety issue: No ]
    Blood pressure was measured using ambulatory blood pressure monitoring (ABPM). A negative change from baseline indicates improvement.

  • Pulse Wave Velocity (PWV) [ Time Frame: Month 6, month 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Major Cardiovascular Events (MACE) [ Time Frame: Month 24 ] [ Designated as safety issue: Yes ]
    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 Measured by Serum Creatinine [ Time Frame: Month 6, month 12, month 24 ] [ Designated as safety issue: No ]
    Serum samples were collected to analyze serum creatinine.

  • Renal Function as Measured by Creatinine Clearance [ Time Frame: Month 6, month 12, month 24 ] [ Designated as safety issue: No ]
    Creatinine clearance was calculated using the Cockroft-Gault formula.

  • Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Month 6, month 12, month 24 ] [ Designated as safety issue: Yes ]
    Estimated GFR was caluclated using the modification of diet in renal disease (MDRD) formula.

  • Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP) [ Time Frame: Baseline, month 6, month 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, month 6, month 24 ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze HbA1c. A negative change from baseline indicates improvement.

  • Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO) [ Time Frame: Baseline, month 6, month 24 ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze MPO. A negative change from baseline indicates improvement.

  • Change From Baseline in the Cardiovascular Biomarker, N-terminal Pro-brain Natriuretic Peptide Fraction (NT-proBNP) [ Time Frame: Baseline, month 6, month 24 ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze NT-proBNP. A negative change from baseline indicates improvement.

  • Change From Baseline in the Cardiovascular Biomarker, Type 1 Procollagen Amino-terminal-propeptide (PINP) [ Time Frame: Baseline, month 6, month 24 ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze PCR. A negative change from baseline indicates improvement.

  • Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP) [ Time Frame: Baseline, month 6, month 24 ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze CRP. A negative change from baseline indicates improvement.

  • Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
    The incidence of BPAR, graft loss, death and lost to follow-up events was calculated using relative frequency.


Enrollment: 71
Study Start Date: August 2010
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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).
Drug: Tacrolimus
Tacrolimus was administrated as Prograf® or Advagraf®, but could not be changed during study.
Other Name: Prograf®, Advagraf®
Drug: 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.
Other Names:
  • Myfortic®
  • Cell-Cept®
Experimental: 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.
Drug: Everolimus
Everolimus was supplied in boxes with 60 tablets. Available tablets: 1.0 mg, 0.5 mg and 0.25 mg.
Other Name: Certican®
Drug: Tacrolimus
Tacrolimus was administrated as Prograf® or Advagraf®, but could not be changed during study.
Other Name: Prograf®, Advagraf®
Drug: 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.
Other Names:
  • Myfortic®
  • Cell-Cept®

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01169701

Locations
Spain
Novartis Investigative Site
Malaga, Andalucia, Spain, 29010
Novartis Investigative Site
Hospitalet de Llobregat, Barcelona, Spain, 08907
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08025
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Barcelona, Cataluña, Spain, 08003
Novartis Investigative Site
Madrid, Spain, 28040
Novartis Investigative Site
Madrid, Spain, 28041
Novartis Investigative Site
Madrid, Spain
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01169701     History of Changes
Other Study ID Numbers: CRAD001AES07  2009-013780-19 
Study First Received: July 22, 2010
Results First Received: April 10, 2015
Last Updated: November 6, 2015
Health Authority: United States: Food and Drug Administration
Spain: Spanish Agency of Medicines

Keywords provided by Novartis:
Renal transplant, everolimus, cardiovascular profile, CNI-free immunosuppression, left ventricular hypertrophy, biopsy proved acute rejection (BPAR)

Additional relevant MeSH terms:
Everolimus
Sirolimus
Mycophenolic Acid
Tacrolimus
Mycophenolate mofetil
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 05, 2016