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

Heart Transplantation Clinical Trial

— MANDELA  

Official title:

A Multi-center, Randomized, Open-label, Parallel Group Study Investigating the Renal Tolerability, Efficacy and Safety of a CNI-free Regimen (Everolimus and MPA) Versus a CNI-regimen With Everolimus in Heart Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00862979
• Other study ID #: CRAD001ADE14
• Secondary ID: 2007-002671-14
• Status: Completed
• Phase: Phase 4
• Start date: February 24, 2009
• Est. completion date: March 6, 2017

Study information

• Verified date: July 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: March 6, 2017
• Est. primary completion date: March 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria:

• Heart transplantation, 3 months prior to enrollment

• Patients have to receive an immunosuppressive regimen with Sandimmun® Optoral, Certican® and corticosteroids

• Sufficient graft function

• Sufficient renal function

• Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at baseline, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility

Exclusion criteria:

• Multi-organ recipients, re-transplantation, or previous transplant with any other organ.

• Patients who are recipients of A-B-O incompatible transplants

• Cold ischemia time >6 hours

• Historical or current peak PRA of > 25% at time of transplantation

• Already existing antibodies against the HLA-type of the receiving transplant Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Heart Transplantation

Intervention

Drug:
• Everolimus (EVR)
Everolimus 0.25mg, 0.75mg or 1.0mg based on blood levels (5-10 ng/mL)
• cyclosporine A (CyA)
10 mg, 25 mg, 50 mg or 100 mg capsule according to blood levels for CNI-regimen group. For CNI-free-regimen dispense on month 6 to 9 only
• tacrolimus (TAC)
0.5 mg, 1 mg, or 5 mg capsule given according to blood levels for CNI-regimen. For CNI-free-regimen give on month 6 to 9 only
• Enteric coated mycophenolate sodium (EC-MPS)
180 mg or 360 mg tablet dosed 1440-2280 mg per day
• mycophenolate mofetil (MMF)
250 mg or 500 mg tablets with a dose of 1500-3000 mg per day
• Corticosteroids
according to local standard: 0.05-0.3 mg/kg of prednisolone or equivalent

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Bad Oeynhausen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Regensburg

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at 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.	Month 18
Secondary	Occurrence of Treatment Failures From Month 6 to 9 and Month 9 to 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.	Month 6 to Month 9; Month 9 to Month 18
Secondary	Occurrence of Major Cardiac Events (MACE) From Month 6 to 18	Major cardiac events (MACE) was defined as one of the following: any death, myocardial infarction, coronary artery bypass grafting	Month 6 to Month 18
Secondary	Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at 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)	Month 12 and 18
Secondary	Serum Creatinine at Month 6, 8, 9, 10 12 and 18	Serum Creatinine is an indicator of renal function measured in the blood	Month 6, 8, 9, 10 12 and 18
Secondary	Reciprocal Creatinine Slope 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.	Between Month 6 and Month 18