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

NCT01169701 | Completed Phase 4 Results

• 2 other identifiers: CRAD001AES072009-013780-19
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 9

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

Conditions

Renal Transplant

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (13)

• Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure

  Baseline, Month 6, month 12, month 24

• Pulse Wave Velocity (PWV)

  Month 6, month 24

• Percentage of Participants With Major Cardiovascular Events (MACE)

  Month 24

• Renal Function Measured by Serum Creatinine

  Month 6, month 12, month 24

• Renal Function as Measured by Creatinine Clearance

  Month 6, month 12, month 24

Study Arms (2)

Tacrolimus

ACTIVE COMPARATOR

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; Drug: Mycophenolic acid (MPA)

Everolimus

EXPERIMENTAL

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; Drug: Tacrolimus; Drug: Mycophenolic acid (MPA)

Interventions

Everolimus DRUG

Everolimus was supplied in boxes with 60 tablets. Available tablets: 1.0 mg, 0.5 mg and 0.25 mg.

Also known as: Certican®

Everolimus

Tacrolimus DRUG

Tacrolimus was administrated as Prograf® or Advagraf®, but could not be changed during study.

Also known as: Prograf®, Advagraf®

Everolimus; Tacrolimus

Mycophenolic acid (MPA) DRUG

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.

Also known as: Myfortic®, Cell-Cept®

Everolimus; Tacrolimus

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08025, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28040, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28041, Spain

Location

Novartis Investigative Site

Madrid, Madrid, Spain

Location

Related Publications (1)

• Cruzado JM, Pascual J, Sanchez-Fructuoso A, Seron D, Diaz JM, Rengel M, Oppenheimer F, Hernandez D, Paravisini A, Saval N, Morales JM; Evita Study Group. Controlled randomized study comparing the cardiovascular profile of everolimus with tacrolimus in renal transplantation. Transpl Int. 2016 Dec;29(12):1317-1328. doi: 10.1111/tri.12862. Epub 2016 Oct 17.

  PMID: 27648523 DERIVED

MeSH Terms

Conditions

Hypertrophy, Left Ventricular

Interventions

Everolimus; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2010
• First Posted: July 26, 2010
• Study Start: August 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: December 7, 2015
• Results First Posted: April 30, 2015

Record last verified: 2015-11

Locations

ES (9)