Heart TransplantationPhase 4MANDELANCT00862979
A Study Investigating the Renal Tolerability, Efficacy, and Safety of a CNI-free Versus a Standard Regimen in de Novo Heart Transplant (HTx) Recipients
A Phase 4 study testing Everolimus (EVR), cyclosporine A (CyA) and tacrolimus (TAC) in people with Heart Transplantation, run by Novartis Pharmaceuticals at 9 sites in Germany.
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Heart Transplantation
- What is being tested?
- Everolimus (EVR), cyclosporine A (CyA) and tacrolimus (TAC)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 162 participants
- Where
- 9 sitesGermany
- Study dates
- 24 Feb 2009to 6 Mar 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Germany9 sites
Novartis Investigative Site
Bad Oeynhausen, 32545
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Leipzig, 04289
Novartis Investigative Site
München, 81377
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Regensburg, 93053
About this study
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
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.
Read the 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.
- Conditions
- Heart Transplantation
- Being tested
- Everolimus (EVR), cyclosporine A (CyA), tacrolimus (TAC), Enteric coated mycophenolate sodium (EC-MPS), mycophenolate mofetil (MMF)
- Keywords
- Heart Transplantation, Cardiac Transplantation, CNI-sparing, renal function, CNI, Cyclosporine A, Everolimus, mycophenolic acid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus (EVR)Drug
Also called Certican, RAD001
Everolimus 0.25mg, 0.75mg or 1.0mg based on blood levels (5-10 ng/mL)
cyclosporine A (CyA)Drug
Also called Sandimmun Optoral
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)Drug
Also called Prograf
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)Drug
Also called Myfortic
180 mg or 360 mg tablet dosed 1440-2280 mg per day
mycophenolate mofetil (MMF)Drug
Also called CellCept
250 mg or 500 mg tablets with a dose of 1500-3000 mg per day
CorticosteroidsDrug
according to local standard: 0.05-0.3 mg/kg of prednisolone or equivalent
| Study group | Role | What they receive |
|---|---|---|
| CNI-regimen | Active comparator | CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids Receives: Drug: Everolimus (EVR); Drug: cyclosporine A (CyA); Drug: tacrolimus (TAC); Drug: Corticosteroids |
| CNI-free-regimen | Experimental | CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids Receives: Drug: Everolimus (EVR); Drug: cyclosporine A (CyA); Drug: tacrolimus (TAC); Drug: Enteric coated mycophenolate sodium (EC-MPS); Drug: mycophenolate mofetil (MMF); Drug: Corticosteroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Month 18
Secondary outcomes (5)
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.
Measured: Month 6 to Month 9; Month 9 to Month 18
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
Measured: Month 6 to Month 18
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)
Measured: Month 12 and 18
Serum Creatinine at Month 6, 8, 9, 10 12 and 18
Serum Creatinine is an indicator of renal function measured in the blood
Measured: Month 6, 8, 9, 10 12 and 18
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.
Measured: Between Month 6 and Month 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2009 (estimated)
- Study start24 Feb 2009
- Primary completion6 Mar 2017
- Study completion6 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart TransplantationStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 162 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00862979
- Sponsor's protocol ID
- CRAD001ADE14
- Other IDs
- 2007-002671-14
- Acronym
- MANDELA
- Status last verified
- Jul 2018
- First submitted
- 16 Mar 2009
- Last updated
- 7 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00862979
- Acronym / sponsor ID
- MANDELA / CRAD001ADE14
- Conditions
- Heart Transplantation
- Keywords
- Heart Transplantation, Cardiac Transplantation, CNI-sparing, renal function, CNI, Cyclosporine A, Everolimus, mycophenolic acid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 162 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 Feb 2009 (actual)
- Primary completion
- 6 Mar 2017 (actual)
- Study completion
- 6 Mar 2017 (actual)
- First posted
- 17 Mar 2009 (estimated)
- Results
- Posted 25 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CNI-regimen | Active comparator | Drug: Everolimus (EVR), Drug: cyclosporine A (CyA), Drug: tacrolimus (TAC), Drug: CorticosteroidsCNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids |
| CNI-free-regimen | Experimental | Drug: Everolimus (EVR), Drug: cyclosporine A (CyA), Drug: tacrolimus (TAC), Drug: Enteric coated mycophenolate sodium (EC-MPS), Drug: mycophenolate mofetil (MMF), Drug: CorticosteroidsCNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Everolimus (EVR)Also: Certican, RAD001Everolimus 0.25mg, 0.75mg or 1.0mg based on blood levels (5-10 ng/mL) | Drug | CNI-free-regimen, CNI-regimen |
| cyclosporine A (CyA)Also: Sandimmun Optoral10 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 | Drug | CNI-free-regimen, CNI-regimen |
| tacrolimus (TAC)Also: Prograf0.5 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 | Drug | CNI-free-regimen, CNI-regimen |
| Enteric coated mycophenolate sodium (EC-MPS)Also: Myfortic180 mg or 360 mg tablet dosed 1440-2280 mg per day | Drug | CNI-free-regimen |
| mycophenolate mofetil (MMF)Also: CellCept250 mg or 500 mg tablets with a dose of 1500-3000 mg per day | Drug | CNI-free-regimen |
| Corticosteroidsaccording to local standard: 0.05-0.3 mg/kg of prednisolone or equivalent | Drug | CNI-free-regimen, CNI-regimen |
Primary outcome
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.
5 secondary outcomes
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
Occurrence of Major Cardiac Events (MACE) From Month 6 to 18
Time frame: Month 6 to Month 18
Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 12 and 18
Time frame: Month 12 and 18
Serum Creatinine at Month 6, 8, 9, 10 12 and 18
Time frame: Month 6, 8, 9, 10 12 and 18
Reciprocal Creatinine Slope Between Month 6 and Month 18
Time frame: Between Month 6 and Month 18
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Everolimus (EVR), cyclosporine A (CyA) and tacrolimus (TAC) in people with Heart Transplantation, run by Novartis Pharmaceuticals at 9 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 18 (time frame: Month 18). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2018.