A Study Investigating the Renal Tolerability, Efficacy, and Safety of a CNI-free Versus a Standard Regimen in de Novo Heart Transplant (HTx) Recipients

Phase 4

Completed

• Conditions: Heart Transplantation
• Interventions: Drug: Everolimus (EVR); Drug: cyclosporine A (CyA); Drug: tacrolimus (TAC); Drug: Corticosteroids; Drug: Enteric coated mycophenolate sodium (EC-MPS); Drug: mycophenolate mofetil (MMF)

• Registration Number: NCT00862979
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This study will assess whether a calcineurin inhibitor (CNI)-free regimen with everolimus and mycophenolic acid is associated with a better renal outcome as compared to the standard regimen containing cyclosporine A (which belongs to the class of CNIs) and everolimus; while both treatments are expected to be comparable with respect to efficacy.

Detailed Description

This study will assess whether a calcineurin inhibitor (CNI)-free regimen with everolimus and mycophenolic acid is associated with a better renal outcome as compared to the standard regimen containing cyclosporine A (which belongs to the class of CNIs) and everolimus; while both treatments are expected to be comparable with respect to efficacy.

Study Timeline

• Study Start: 2009-02-24
• Study First Submitted: 2009-03-16
• Study First Submitted QC: 2009-03-16
• Study First Posted: 2009-03-17
• Primary Completion: 2017-03-06
• Study Completion: 2017-03-06
• Results First Submitted: 2018-03-05
• Results First Submitted QC: 2018-05-23
• Results First Posted: 2018-06-25
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-09
• Last Update Posted: 2018-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 162

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CNI-free-regimen	mycophenolate mofetil (MMF)	CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
CNI-regimen	tacrolimus (TAC)	CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids
CNI-regimen	Corticosteroids	CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids
CNI-free-regimen	Everolimus (EVR)	CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
CNI-free-regimen	tacrolimus (TAC)	CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
CNI-regimen	Everolimus (EVR)	CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids
CNI-regimen	cyclosporine A (CyA)	CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids
CNI-free-regimen	cyclosporine A (CyA)	CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
CNI-free-regimen	Enteric coated mycophenolate sodium (EC-MPS)	CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
CNI-free-regimen	Corticosteroids	CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids

Primary Outcome Measures

Name	Time	Method
Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 18	Month 18	Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 18 cGFR (in mL/min/1.73 m2) = 186.3\*(C-1.154)\*(A-0.203)\*G\*R where C = the 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

Name	Time	Method
Occurrence of Treatment Failures From Month 6 to 9 and Month 9 to 18	Month 6 to Month 9; Month 9 to Month 18	Treatment failure was defined as composite endpoint of biopsy proven acute rejection of ISHLT 1990 grade ≥ 3A resp. ISHLT 2004 grade ≥ 2R, acute rejection episodes associated with hemodynamic compromise, graft loss / re-transplant, death, loss to follow up (at least one condition must be present). If participant had an occurrence in each period it was counted for each period.
Occurrence of Major Cardiac Events (MACE) From Month 6 to 18	Month 6 to Month 18	Major cardiac events (MACE) was defined as one of the following: any death, myocardial infarction, coronary artery bypass grafting
Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 12 and 18	Month 12 and 18	Calculated Glomerular Filtration Rate (cGFR) according to Cockcroft-Gault at Month 12 and 18. For men: GFR=(140-Age) x Body weight (kg) / 72 x Serum Creatinine (mg/dl) For women: GFR=0.85 (140 -Age) x Body weight(kg)/ 72 x Serum Creatinine (mg/dl)
Serum Creatinine at Month 6, 8, 9, 10 12 and 18	Month 6, 8, 9, 10 12 and 18	Serum Creatinine is an indicator of renal function measured in the blood
Reciprocal Creatinine Slope Between Month 6 and Month 18	Between Month 6 and Month 18	Reciprocal Creatinine Slope is an indication of renal function over time with a higher slope value indicating an improvement in renal function.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇩🇪 Regensburg, Germany