Investigation of renal tolerability, efficacy and safety of a CNI-free regimen versus a low-dose CNI- regimen in de novo heart transplant recipients

A 15-month, multi-center, randomized, open-label, parallel group study investigating the renal tolerability, efficacy and safety of a CNI-free regimen (Certican® and MPA) versus a low-dose CNI- regimen (Sandimmun® Optoral and Certican®) in de novo heart transplant recipients - MANDELA

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2007-002671-14-DE

Enrollment

200

Registered

2007-12-17

Start date

2008-02-18

Completion date

Unknown

Last updated

2018-03-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

heart transplantation MedDRA version: 14.1 Level: PT Classification code 10019314 Term: Heart transplant System Organ Class: 10042613 - Surgical and medical procedures

Interventions

Trade Name: Certican Tabletten Product Name: RAD001 Product Code: RAD001 Pharmaceutical Form: Tablet INN or Proposed INN: Everolimus CAS Number: 159351-69-6 Current Sponsor code: RAD001 Concentration

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Males or females, aged 18 – 70 years 2. Recipients of de novo cardiac transplants, 3 months prior to enrolment 3. Patients with sufficient renal function, i.e. GFR >30 and =65 years) yes F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1. Multi-organ recipients, re-transplantation, or previous transplant with any other organ. 2. Donor age: 70 years 3. Patients who are recipients of A-B-O incompatible transplants 4. Calculated ischemia time >6 hours (calculated ischemia time = total ischemia time MINUS tme of the transplant in the OCS (Organ Care System) 5. Patients with a historical or current peak PRA of > 25% at time of transplantation 6. Patients with already existing antibodies against the HLA-type of the receiving transplant 7. Patients with insufficient graft function, i.e.who suffered from severe rejection (i.e. more than 2 episodes of ISHLT 1990 > Grade 2 resp. ISHLT 2004 3 times UNL) 16. Presence of severe hypercholesterolemia (=350 mg/dL; =9 mmol/L) or hypertriglyceridemia (= 750 mg/dL; =8.5 mmol/L) 17. History of significant coagulopathy or medical condition requiring long term anticoagulation after transplantation (low dose aspirin treatment is allowed) 18. Females of childbearing potential who are planning to become pregnant, who are pregnant or lactating, and/or who are unwilling to use effective means of contraception 19. Presence of a clinically significant infection requiring continued therapy, severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus that in the opinion of the investigator would interfere with the appropriate conduct of the study 20. Evidence of drug or alcohol abuse 21. Patients receiving drugs known to significantly interact with CsA and/or everolimus according to the list provided in Appendix 3 to this protocol. Especially the administration of terfenadine, astemizole, or cisapride as well as strong inducers or inhibitors of cytochrome P450 3A4 will not be allowed.

Design outcomes

Primary

Measure	Time frame
Timepoint(s) of evaluation of this end point: Month 18;Secondary Objective: Secondary objectives of this trial are: • to asses occurrence of treatment failures up to or at Month 18 post Tx, while treatment failure is defined as a composite endpoint of biopsy proven acute rejection of ISHLT 1990 grade =3A, acute rejection episodes associated with hemodynamic compromise, graft loss / re-transplant, death, loss to follow up (at least one condition must be present) • to assess incidence of MACE and each of its components at Month 18 post Tx • to assess renal function by glomerular filtration rate - Cockcroft-Gault method - at Month 12 and 18 post Tx • to assess renal function (serum creatinine) and evolution of renal function between Month 6 and 18 post Tx (creatinine slope) • to assess safety and tolerability at Month 6, 9 and 18 post Tx (according to safety parameters ;Main Objective: The primary objective of this trial is to demonstrate superiority of a CNI-free regimen with respect to the renal function at Month 18 post Tx assessed by glomerular filtration rate – MDRD method – as compared to a low dose CNI-based regimen in de novo heart transplant patients.;Primary end point(s): The primary variable for assessment of renal function is the glomerular filtration rate (GFR) at Month 18, as assessed by the MDRD method.	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: Month 18;Secondary Objective: Secondary objectives of this trial are: • to asses occurrence of treatment failures up to or at Month 18 post Tx, while treatment failure is defined as a composite endpoint of biopsy proven acute rejection of ISHLT 1990 grade =3A, acute rejection episodes associated with hemodynamic compromise, graft loss / re-transplant, death, loss to follow up (at least one condition must be present) • to assess incidence of MACE and each of its components at Month 18 post Tx • to assess renal function by glomerular filtration rate - Cockcroft-Gault method - at Month 12 and 18 post Tx • to assess renal function (serum creatinine) and evolution of renal function between Month 6 and 18 post Tx (creatinine slope) • to assess safety and tolerability at Month 6, 9 and 18 post Tx (according to safety parameters ;Main Objective: The primary objective of this trial is to demonstrate superiority of a CNI-free regimen with respect to the renal function at Month 18 post Tx assessed by glomerular filtration rate – MDRD method – as compared to a low dose CNI-based regimen in de novo heart transplant patients.;Primary end point(s): The primary variable for assessment of renal function is the glomerular filtration rate (GFR) at Month 18, as assessed by the MDRD method.

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Secondary

Measure	Time frame
Secondary end point(s): • to asses occurrence of treatment failures up to or at Month 18 post Tx, while treatment failure is defined as a composite endpoint of biopsy proven acute rejection of ISHLT 1990 grade =3A, acute rejection episodes associated with hemodynamic compromise, graft loss / re-transplant, death, loss to follow up (at least one condition must be present) • to assess incidence of MACE and each of its components at Month 18 post Tx • to assess renal function by glomerular filtration rate - Cockcroft-Gault method - at Month 12 and 18 post Tx • to assess renal function (serum creatinine) and evolution of renal function between Month 6 and 18 post Tx (creatinine slope) • to assess safety and tolerability at Month 6, 9 and 18 post Tx (according to safety parameters ;Timepoint(s) of evaluation of this end point: see E.5.2	—

Measure

Time frame

Secondary end point(s): • to asses occurrence of treatment failures up to or at Month 18 post Tx, while treatment failure is defined as a composite endpoint of biopsy proven acute rejection of ISHLT 1990 grade =3A, acute rejection episodes associated with hemodynamic compromise, graft loss / re-transplant, death, loss to follow up (at least one condition must be present) • to assess incidence of MACE and each of its components at Month 18 post Tx • to assess renal function by glomerular filtration rate - Cockcroft-Gault method - at Month 12 and 18 post Tx • to assess renal function (serum creatinine) and evolution of renal function between Month 6 and 18 post Tx (creatinine slope) • to assess safety and tolerability at Month 6, 9 and 18 post Tx (according to safety parameters ;Timepoint(s) of evaluation of this end point: see E.5.2

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Countries

Germany

Contacts

Public ContactMedizinischer Infoservice

Novartis Pharma GmbH

infoservice.novartis@novartis.com+491802232300

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026