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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01114529
First received: April 27, 2010
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

The purpose of this study is 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 is designed to evaluate the impact of a CNI-free regimen on evolution of cardiovascular parameters in de novo renal allograft recipients


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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
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:

Primary Outcome Measures:
  • Assessment of renal function by estimated Glomerular Filtration Rate [ Time Frame: at 12 months post-transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Composite efficacy failure as treated biopsy proven acute rejection (BPAR ), graft loss or death [ Time Frame: at 12 months post-transplantation ] [ Designated as safety issue: No ]
  • Improvement of Left Ventricular Hypertrophy (LVH) as assessed by LV mass index (LVMi) using echocardiogram [ Time Frame: at 12 months post-transplantation ] [ Designated as safety issue: No ]
  • incidence, time to event and severity of treated BPAR ≥ IB; incidence of BPAR that need antibody treatment; incidence of humoral rejection; incidence of treated BPAR ≥ IB, [ Time Frame: at 12 and 24 months post-transplantation ] [ Designated as safety issue: No ]
  • Incidence, time to event and severity of any acute rejection (suspected AR, treated acute AR, Biopsy AR, treated biopsy proven AR, subclinical AR) [ Time Frame: at 12 and 24 months post-transplantation ] [ Designated as safety issue: No ]
  • Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: at 12 and 24 months post-transplantation ] [ Designated as safety issue: No ]

Enrollment: 717
Study Start Date: August 2010
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01114529     History of Changes
Other Study ID Numbers: CRAD001A2429, 2009-015918-22
Study First Received: April 27, 2010
Last Updated: June 17, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Everolimus
Sirolimus
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 18, 2014