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

Phase 3
Completed
Conditions
Kidney Transplantation
Interventions
Registration Number
NCT01114529
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
828
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
EverolimusEverolimusConversion from CNI to everolimus in combination with Myfortic and steroids
Calcineurin inhibitor, Prograf or NeoralPrograf or NeoralControl arm: CNI continuation, either Prograf or Neoral in combination with Myfortic and steroids
Primary Outcome Measures
NameTimeMethod
Estimated Glomerular Filtration Rate (eGFR)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
NameTimeMethod
Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24at 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 24Randomization, 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)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

Trial Locations

Locations (1)

Novartis Investigative Site

🇹🇷

Istanbul, Turkey

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