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Completed

NCT Number: NCT00862979

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

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.

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Key information

Conditions

Heart Transplantation

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Novartis Investigative Site, Bad Oeynhausen, Germany

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Everolimus (EVR)

Drug

Everolimus 0.25mg, 0.75mg or 1.0mg based on blood levels (5-10 ng/mL)

Other names: Certican, RAD001

cyclosporine A (CyA)

Drug

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

Other names: Sandimmun Optoral

Tacrolimus (TAC)

Drug

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

Other names: Prograf

Enteric coated mycophenolate sodium (EC-MPS)

Drug

180 mg or 360 mg tablet dosed 1440-2280 mg per day

Other names: Myfortic

Mycophenolate Mofetil (MMF)

Drug

250 mg or 500 mg tablets with a dose of 1500-3000 mg per day

Other names: CellCept

Corticosteroids

Drug

according to local standard: 0.05-0.3 mg/kg of prednisolone or equivalent

Primary outcomes

  1. Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 18

    Time frame: 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 outcomes

  1. Occurrence of Treatment Failures From Month 6 to 9 and Month 9 to 18

    Time frame: 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.

  2. Occurrence of Major Cardiac Events (MACE) From Month 6 to 18

    Time frame: Month 6 to Month 18

    Major cardiac events (MACE) was defined as one of the following: any death, myocardial infarction, coronary artery bypass grafting

  3. Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 12 and 18

    Time frame: 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)

  4. Serum Creatinine at Month 6, 8, 9, 10 12 and 18

    Time frame: Month 6, 8, 9, 10 12 and 18

    Serum Creatinine is an indicator of renal function measured in the blood

  5. Reciprocal Creatinine Slope Between Month 6 and Month 18

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: MANDELA

Important dates

Study start
2009
Primary completion
2017
Study completion
2017
First posted
Mar 17, 2009
Registry last updated
Aug 7, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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