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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01114529
First received: April 27, 2010
Last updated: April 24, 2017
Last verified: April 2017
  Purpose
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

Condition Intervention Phase
Kidney Transplantation Drug: Everolimus Drug: Prograf or Neoral Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.

  • 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.

  • 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


Enrollment: 828
Actual Study Start Date: August 9, 2010
Study Completion Date: October 30, 2014
Primary Completion Date: October 30, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus
Conversion from CNI to everolimus in combination with Myfortic and steroids
Drug: Everolimus
Early CNI to everolimus conversion
Other Name: 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 Name: Tacrolimus or Cyclosporine

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01114529

  Show 77 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01114529     History of Changes
Other Study ID Numbers: CRAD001A2429
2009-015918-22 ( EudraCT Number )
Study First Received: April 27, 2010
Results First Received: October 26, 2015
Last Updated: April 24, 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
de novo renal allograft recipients
renal allograft function
CNI-free regimen

Additional relevant MeSH terms:
Everolimus
Sirolimus
Tacrolimus
Cyclosporine
Cyclosporins
Calcineurin Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 27, 2017