Efficacy, Safety and Evolution of Cardiovascular Parameters in Renal Transplant Recipients (ELEVATE)

April 24, 2017 updated by: Novartis Pharmaceuticals

A 24-month, Multi-center, Open-label, Randomized, Controlled Trial to Investigate Efficacy, Safety and Evolution of Cardiovascular Parameters in de Novo Renal Transplant Recipients After Early Calcineurin Inhibitor to Everolimus Conversion

The purpose of this study was to determine whether an early Calcineurin Inhibitor (CNI) to everolimus conversion at 10-14 weeks post transplantation improves renal allograft function without compromising efficacy compared to standard CNI treatment in de novo renal allograft recipients. In addition, the study was designed to evaluate the impact of a CNI-free regimen on evolution of cardiovascular parameters in de novo renal allograft recipients

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This was a 24-month, multi-center, randomized, open-label trial with two parallel arms in adult de novo renal allograft recipients. The study consisted of a run-in period from transplantation to Randomization and a treatment period from Randomization until Month 24. At baseline visit, patients were transplanted and entered the run-in period from transplantation (Baseline) to Randomization (week 10-14 post-transplantation). At Week 10-14, eligible patients were randomized into one of the 2 treatment arms: standard CNIs and Myfortic versus everolimus and Myfortic and entered the treatment period of the study from Randomization to Month 24. Patients in both arms received steroids as per center practice and in any caseat least 5 mg/Day. At Randomization, patients were stratified according to their renal allograft function and previous cardiovascular events. The main analysis was performed at Month 12 and the follow-up analysis was performed at Month 24.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
828

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Cordoba, Argentina, X5016KEH
        • Novartis Investigative Site
      • Cordoba, Argentina, X5022CPU
        • Novartis Investigative Site
      • Cordoba, Argentina, X5016JDA
        • Novartis Investigative Site
      • Santa Fe, Argentina, S3000EPV
        • Novartis Investigative Site
    • Buenos Aires
      • Caba, Buenos Aires, Argentina, C1118AAT
        • Novartis Investigative Site
      • San Martin, Buenos Aires, Argentina, C1107BEA
        • Novartis Investigative Site
    • Chaco
      • Resistencia, Chaco, Argentina, H3508AZP
        • Novartis Investigative Site
  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Novartis Investigative Site
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Novartis Investigative Site
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Novartis Investigative Site
      • Melbourne, Victoria, Australia, 3050
        • Novartis Investigative Site
  • Austria
      • Linz, Austria, A-4010
        • Novartis Investigative Site
      • Linz, Austria, A-4020
        • Novartis Investigative Site
      • Wien, Austria, 1090
        • Novartis Investigative Site
  • Belgium
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
  • Estonia
      • Tartu, Estonia, 51014
        • Novartis Investigative Site
  • France
      • Brest, France, 29200
        • Novartis Investigative Site
      • Nice Cedex 1, France, 06602
        • Novartis Investigative Site
      • Toulouse Cedex 4, France, 31054
        • Novartis Investigative Site
      • Tours Cedex, France, 37044
        • Novartis Investigative Site
      • Vandoeuvre Les Nancy, France, 54511
        • Novartis Investigative Site
  • Germany
      • Aachen, Germany, 52074
        • Novartis Investigative Site
      • Berlin, Germany, 12203
        • Novartis Investigative Site
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Frankfurt am Main, Germany, 60596
        • Novartis Investigative Site
      • Hamburg, Germany, 20246
        • Novartis Investigative Site
      • Hannover Muenden, Germany, 34346
        • Novartis Investigative Site
      • Heidelberg, Germany, 69120
        • Novartis Investigative Site
      • Muenster, Germany, 48149
        • Novartis Investigative Site
  • Greece
      • Athens, Greece, GR 11527
        • Novartis Investigative Site
      • Athens, Greece, GR-106 76
        • Novartis Investigative Site
      • Patras, Greece, 265 00
        • Novartis Investigative Site
  • India
      • New Delhi, India, 110044
        • Novartis Investigative Site
    • Andhra Pradesh
      • Vishakhapatnam, Andhra Pradesh, India
        • Novartis Investigative Site
    • Delhi
      • New Delhi, Delhi, India, 110017
        • Novartis Investigative Site
    • Karnataka
      • Bangalore, Karnataka, India, 560 055
        • Novartis Investigative Site
    • Uttar Pradesh
      • Lucknow, Uttar Pradesh, India, 226014
        • Novartis Investigative Site
  • Italy
    • BO
      • Bologna, BO, Italy, 40138
        • Novartis Investigative Site
    • PD
      • Padova, PD, Italy, 35128
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00144
        • Novartis Investigative Site
    • SI
      • Siena, SI, Italy, 53100
        • Novartis Investigative Site
    • TO
      • Torino, TO, Italy, 10126
        • Novartis Investigative Site
  • Latvia
      • Riga, Latvia, 1002
        • Novartis Investigative Site
  • Lithuania
      • Vilnius, Lithuania, LT-08661
        • Novartis Investigative Site
  • Mexico
      • Aguascalientes, Mexico, 20230
        • Novartis Investigative Site
      • Veracruz, Mexico, 91700
        • Novartis Investigative Site
    • Coahuila
      • Torreón, Coahuila, Mexico, 27250
        • Novartis Investigative Site
    • Distrito Federal
      • Mexico, Distrito Federal, Mexico, 14080
        • Novartis Investigative Site
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Novartis Investigative Site
      • Groningen, Netherlands, 9713 GZ
        • Novartis Investigative Site
      • Leiden, Netherlands, 2300 RC
        • Novartis Investigative Site
  • Norway
      • Oslo, Norway, 0424
        • Novartis Investigative Site
  • Portugal
      • Lisbon, Portugal, 1069-166
        • Novartis Investigative Site
      • Porto, Portugal, 4200-319
        • Novartis Investigative Site
    • Lisboa
      • Carnaxide - Linda-A-Velha, Lisboa, Portugal, 2790-134
        • Novartis Investigative Site
  • Romania
    • Jud Cluj
      • Cluj-Napoca, Jud Cluj, Romania, 400006
        • Novartis Investigative Site
  • Russian Federation
      • Krasnodar, Russian Federation, 350086
        • Novartis Investigative Site
      • Moscow, Russian Federation, 123182
        • Novartis Investigative Site
      • Moscow, Russian Federation, 115446
        • Novartis Investigative Site
      • Nizhnii Novgorod, Russian Federation, 603000
        • Novartis Investigative Site
      • Novosibirsk, Russian Federation, 630087
        • Novartis Investigative Site
      • S.-Petersburg, Russian Federation, 192242
        • Novartis Investigative Site
      • Samara, Russian Federation, 443079
        • Novartis Investigative Site
      • Volzhskiy, Russian Federation, 404120
        • Novartis Investigative Site
  • Spain
      • Zaragoza, Spain, 50009
        • Novartis Investigative Site
    • Andalucia
      • Malaga, Andalucia, Spain, 29010
        • Novartis Investigative Site
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
      • Barcelona, Catalunya, Spain, 08003
        • Novartis Investigative Site
    • Cataluña
      • Hospitalet de Llobregat, Cataluña, Spain, 08907
        • Novartis Investigative Site
    • Galicia
      • A Coruña, Galicia, Spain, 15006
        • Novartis Investigative Site
  • Thailand
      • Bangkok, Thailand, 10330
        • Novartis Investigative Site
    • THA
      • Khon Kaen, THA, Thailand, 40002
        • Novartis Investigative Site
  • Turkey
      • Antalya, Turkey, 07000
        • Novartis Investigative Site
      • Büyükçekmece / Ýstanbul, Turkey, 34520
        • Novartis Investigative Site
      • Fatih / Istanbul, Turkey, 34098
        • Novartis Investigative Site
      • Istanbul, Turkey, 34093
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria at Baseline:

  • Male or female renal allograft recipients at least 18 years old.
  • Written informed consent.
  • Patient receiving a primary or secondary kidney transplant from a cadaveric or living unrelated-/related donor.
  • Cold ischemia time (CIT) < 24 hours.
  • Negative pregnancy test for female patients.

Inclusion Criteria at Randomization:

  • Patients on CNI (TAC or CsA) + Myfortic + steroids.
  • Serum creatinine < 2.8 mg/dL (250 µmol/L) and an actual eGFR (MDRD4) ≥ 25 mL/min/1.73m exp2 (without renal replacement therapy).

Exclusion Criteria at Baseline:

Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

  • Recipient of multiple organ transplants.
  • Recipient of ABO incompatible allograft or a positive cross-match.
  • Panel Reactive Antibodies (PRA) level ≥ 30 %.
  • Positive test for human immunodeficiency virus (HIV).
  • Patient receiving an allograft from a Hepatitis B surface Antigen (HBsAg) or a Hepatitis C Virus (HCV) positive donor.
  • HBsAg and/or a HCV positive patient with evidence of elevated LFTs (ALT/AST levels ≥ 2.5 times ULN).
  • Severe restrictive or obstructive pulmonary disorders.
  • Patient with severe allergy requiring acute or chronic treatment or hypersensitivity to any of the study drugs or similar drugs.
  • Severe hypercholesterolemia or hypertriglyceridemia.
  • Low platelet count.
  • Low white blood cell count.
  • History of malignancy of any organ system

Exclusion Criteria at Randomization:

  • Graft loss.
  • Patient on renal replacement therapy.
  • Patient who experienced severe humoral and/or cellular rejection (BANFF ≥ IIb).
  • Patient with ≥ 2 episodes of AR or an AR episode that needed antibody treatment.
  • Patient with ongoing or currently treated AR (2 weeks prior to randomization).
  • Proteinuria > 1 g/day.
  • Patients with recurrence of Focal Segmental Glomerulosclerosis (FSGS).
  • Low platelet count; Low white blood cell count; Low absolute neutrophil count; Low hemoglobin.
  • Severe liver disease.
  • Systemic infection requiring continued therapy that would interfere with the objectives of the study.
  • Severe hypercholesterolemia or hypertriglyceridemia.
  • Patients with ongoing wound healing problems, clinically significant infection requiring continued therapy.
  • Presence of intractable immunosuppressant complications or side effects.
  • Patients on anticoagulants that prevents renal allograft biopsy.
  • Use of prohibited medication.
  • Use of immunosuppressive agents not utilized in the protocol.
  • Pregnant or nursing (lactating) women.
  • Women of child-bearing potential not using a highly effective method of birth control.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Everolimus
Conversion from CNI to everolimus in combination with Myfortic and steroids
Drug: Everolimus
Early CNI to everolimus conversion
Other Names:
  • Certican, Zortress, RAD001
Active Comparator: Calcineurin inhibitor, Prograf or Neoral
Control arm: CNI continuation, either Prograf or Neoral in combination with Myfortic and steroids
Drug: Prograf or Neoral
Active CNI-based control (Prograf or Neoral)
Other Names:
  • Tacrolimus or Cyclosporine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Estimated Glomerular Filtration Rate (eGFR)
Time Frame: Month 12
Assessment of renal function by comparing change from randomization to Month 12 in eGFR (MDRD4) between treatment arms (Full analysis set). Renal function was assessed by estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. MDRD formula: GFR [mL/min/1.73m˄2] = 186.3*(C˄-1.154)*(A˄-0.203)*G*R. DEFINITIONS: C = serum concentration of creatinine [mg/dL]; A = age [years]; G = 0.742 when gender is female, otherwise G = 1; R = 1.21 when race is black, otherwise R = 1
Month 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24
Time Frame: at 12 months and month 24 post-transplantation
Efficacy failure rate used the composite endpoint of: (1) treated biopsy-proven acute rejection (BPAR)*, (2) graft loss**, or (3) death . *A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. **Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted.
at 12 months and month 24 post-transplantation
Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24
Time Frame: Randomization, Month 12 and Month 24
Evolution of left ventricular mass and hypertrophy were evaluated by left ventricular mass index (LVMi) assessed by echocardiography. LVMi is derived using a standard formula from dimensional measurements on the echocardiogram. Analysis of covariance was applied with treatment, center (as a random effect), and donor type as factors and LVMi at Randomization as covariate.
Randomization, Month 12 and Month 24
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis)
Time Frame: at 24 months post-transplantation
(treated BPAR ≥ IB, graft loss or death)A comparison of the incidence rates for the individual components of the composite efficacy endpoint between treatment arms
at 24 months post-transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 9, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 30, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 27, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 3, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 30, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CRAD001A2429
  • 2009-015918-22 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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