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
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
2 other identifiers
interventional
162
1 country
9
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4
Started Feb 2009
Longer than P75 for phase_4
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 24, 2009
CompletedFirst Submitted
Initial submission to the registry
March 16, 2009
CompletedFirst Posted
Study publicly available on registry
March 17, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 6, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
March 6, 2017
CompletedResults Posted
Study results publicly available
June 25, 2018
CompletedAugust 7, 2018
July 1, 2018
8 years
March 16, 2009
March 5, 2018
July 9, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (5)
Occurrence of Treatment Failures From Month 6 to 9 and Month 9 to 18
Month 6 to Month 9; Month 9 to Month 18
Occurrence of Major Cardiac Events (MACE) From Month 6 to 18
Month 6 to Month 18
Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 12 and 18
Month 12 and 18
Serum Creatinine at Month 6, 8, 9, 10 12 and 18
Month 6, 8, 9, 10 12 and 18
Reciprocal Creatinine Slope Between Month 6 and Month 18
Between Month 6 and Month 18
Study Arms (2)
CNI-regimen
ACTIVE COMPARATORCNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids
CNI-free-regimen
EXPERIMENTALCNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
Interventions
Everolimus 0.25mg, 0.75mg or 1.0mg based on blood levels (5-10 ng/mL)
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
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
180 mg or 360 mg tablet dosed 1440-2280 mg per day
250 mg or 500 mg tablets with a dose of 1500-3000 mg per day
according to local standard: 0.05-0.3 mg/kg of prednisolone or equivalent
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
Novartis Investigative Site
Bad Oeynhausen, 32545, Germany
Novartis Investigative Site
Berlin, 13353, Germany
Novartis Investigative Site
Hamburg, 20246, Germany
Novartis Investigative Site
Hanover, 30625, Germany
Novartis Investigative Site
Heidelberg, 69120, Germany
Novartis Investigative Site
Leipzig, 04289, Germany
Novartis Investigative Site
München, 81377, Germany
Novartis Investigative Site
Münster, 48149, Germany
Novartis Investigative Site
Regensburg, 93053, Germany
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 16, 2009
First Posted
March 17, 2009
Study Start
February 24, 2009
Primary Completion
March 6, 2017
Study Completion
March 6, 2017
Last Updated
August 7, 2018
Results First Posted
June 25, 2018
Record last verified: 2018-07