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

Purpose

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.

Condition	Intervention	Phase
Heart Transplantation	Drug: Sandimmun Optoral / Tac + RAD001 Drug: MPA + RAD001	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A 15-month, Multi-center, Randomized, Open-label, Parallel Group Study Investigating the Renal Tolerability, Efficacy, and Safety of a CNI-free Regimen (Everolimus and Mycophenolic Acid) Versus a Standard Regimen (Cyclosporine A and Everolimus) in de Novo Heart Transplant Recipients

Resource links provided by NLM:

MedlinePlus related topics: Heart Transplantation Kidney Tests

Drug Information available for: Mycophenolic acid Mycophenolate sodium Sirolimus Cyclosporine Mycophenolate mofetil hydrochloride Mycophenolate mofetil Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Renal function assessed as glomerular filtration rate (GFR) - MDRD formula [ Time Frame: 18 months after heart transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Occurrence of treatment failures [ Time Frame: up to or at Month 18 ] [ Designated as safety issue: Yes ]
incidence of major cardiac events and each of its components [ Time Frame: Month 18 ] [ Designated as safety issue: Yes ]
renal function by GFR - Cockcroft-Gault method [ Time Frame: Month 12 and 18 ] [ Designated as safety issue: No ]
renal function and evolution of renal function (creatinine slope) [ Time Frame: between Month 6 and Month 18 ] [ Designated as safety issue: No ]
safety and tolerability [ Time Frame: Month 6, 9 and 18 ] [ Designated as safety issue: Yes ]


Enrollment:	178
Study Start Date:	February 2009
Estimated Study Completion Date:	April 2017
Estimated Primary Completion Date:	April 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Certican CNI MMF OR Myfortic, Certican®, Sandimmun® optoral reduced	Drug: Sandimmun Optoral / Tac + RAD001 RAD001 / CNI group
Experimental: Certican MMF or Myfortic+ Everolimus + corticosteroids	Drug: MPA + RAD001 RAD001 / MPA group

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.

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

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: NCT00862979

Locations


Germany
Novartis Investigative Site
Bad Oeynhausen, Germany, 32545
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Leipzig, Germany, 04289
Novartis Investigative Site
Muenster, Germany, 48149
Novartis Investigative Site
München, Germany, 81377
Novartis Investigative Site
Regensburg, Germany, 93053

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00862979 History of Changes
Other Study ID Numbers:	CRAD001ADE14 2007-002671-14
Study First Received:	March 16, 2009
Last Updated:	August 2, 2016
Health Authority:	United States: Food and Drug Administration Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:


Heart Transplantation Cardiac Transplantation CNI-sparing renal function	CNI Cyclosporine A Everolimus enteric coated mycophenolic acid

Additional relevant MeSH terms:


Everolimus Sirolimus Mycophenolic Acid Cyclosporins Cyclosporine Mycophenolate mofetil 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 Calcineurin Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016

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