Estudio de no inferioridad, multicéntrico, abierto, aleatorizado, de 24 meses de seguimiento, de eficacia y seguridad, que compara dos exposiciones a Certican ®(everolimus) con control de la concentración y dosis reducidas de Sandimmun Neoral ®(Ciclosporina para microemulsión) frente a 3.0 g de MMF y dosis estándares de Sandimmun Neoral®, en pacientes receptores de un trasplante cardíaco de novo.

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2005-003413-32-ES
• Date of registration: 18/04/2006
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmaceútica S.A
• Public title: Estudio de no inferioridad, multicéntrico, abierto, aleatorizado, de 24 meses de seguimiento, de eficacia y seguridad, que compara dos exposiciones a Certican ®(everolimus) con control de la concentración y dosis reducidas de Sandimmun Neoral ®(Ciclosporina para microemulsión) frente a 3.0 g de MMF y dosis estándares de Sandimmun Neoral®, en pacientes receptores de un trasplante cardíaco de novo.
• Scientific title: Estudio de no inferioridad, multicéntrico, abierto, aleatorizado, de 24 meses de seguimiento, de eficacia y seguridad, que compara dos exposiciones a Certican ®(everolimus) con control de la concentración y dosis reducidas de Sandimmun Neoral ®(Ciclosporina para microemulsión) frente a 3.0 g de MMF y dosis estándares de Sandimmun Neoral®, en pacientes receptores de un trasplante cardíaco de novo.
• Date of first enrolment: 06/06/2006
• Target sample size: 630
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003413-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: yes; Placebo: Other:
• Phase: Human pharmacology (Phase I): Therapeutic exploratory (Phase II): Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV):

Countries of recruitment

Austria, Belgium, Denmark, Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female cardiac recipients 18-70 years of age undergoing primary heart transplantation.
• Patients who have given written informed consent to participate in the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Calculated creatinine clearance <40 ml/min at screening (MDRD Formula)
•Patients with platelet count <50,000/mm at the evaluation before randomization.
•Patients who are recipients of multiple solid organ transplants.
•Patients who are recipients of ABO incompatible transplants
•Patients with active systemic infection.
•Patients receiving drugs used for non-approved indications in the 30 days prior to study entry.
•Patients receiving induction therapy in non induction center
•Patients not receiving induction therapy in an induction center
•Induction therapy other than Simulect
•Presence of severe hypercholesterolemia (=?350 mg/dL; =?9 mmol/L) or hypertriglyceridemia (= 750 mg/dL; =?8.5 mmol/L) before randomization.
•Patients with an absolute neutrophil count of =?1,500/mm3 or white blood cell count of = 4000/mm3 at baseline before surgery
•Patients with a history of significant coagulopathy or medical condition requiring long term anti-coagulation after transplantation (low dose aspirin treatment is allowed)
•Patients who are HIV-positive or Hepatitis C (PCR+ only) or B surface antigen positive. Laboratory results obtained within 6 months prior to study entry are acceptable.
•Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C (PCR+ only) are excluded
•Patients being treated with terfenadine, astemoizole, or cisapride
•Patients with any past (within the past 5 years) or present malignancy (other than excised basal cell carcinoma)
•Patients with a known hypersensitivity to drugs of this class.
•Patients with donor greater than 65 years and/or with known donor heart disease at the time of transplant.
•Patients who are treated with drugs strong inducers or inhibitors of cytochrome P450 3A4.
•Cold ischemia time >6 hours.
•Unable to take oral medication.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Trasplante Cardiaco de novo De novo heart transplantation

Intervention(s)

Trade Name: Certican®
Product Name: Certican®
Product Code: RAD001 Everolimus
Pharmaceutical Form: Tablet
INN or Proposed INN: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.75-

Trade Name: Cellcept®
Product Name: Cellcept®
Product Code: mycophenolate mofetil
Pharmaceutical Form: Tablet
INN or Proposed INN: mycophenolate mofetil
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Sandimmun Neoral®
Product Name: Sandimmun Neoral®
Pharmaceutical Form: Tablet
INN or Proposed INN: CICLOSPORINA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Primary end point(s): The primary objective of the study is to show that either one of the Certican arms is non-inferior to the MMF treatment arm, with respect to primary efficacy failure rate at 12 months

To test non-inferiority of Certican 1.5mg dose to MMF

Main Objective: To assess if comparable rates of the composite efficacy failure (biopsy-proven acute rejection of ISHLT grade = 3A, acute rejection episodes associated with hemodynamic compromise, graft loss/re-transplant, death, or loss to follow-up) are achieved in cohorts of de novo heart recipients treated with Certican-reduced Neoral versus MMF-Neoral standard dose at 12 months after initial dose of study medication

Secondary Objective: • To assess incidence rate of graft loss/re-transplant, death or loss to follow-up at 12 months
• To demonstrate that similar renal function assessed by calculated GFR by MDRD formula (Coresh et. al. 2003) is achieved in the Certican treatment arm compared to the MMF treatment arm within 12 months of initial dose of study medication.

• IVUS sub-study analysis (sub-study performed only in selected centers) - To evaluate the change in average maximum intimal thickness from Baseline and the incidence of chronic rejection (allograft vasculopathy) in patients receiving two oral doses of RAD and those receiving MMF as measured by intravascular ultrasound (IVUS) at 12 months.

Secondary ID(s)

2005-003413-32-GB

CRAD001A2310

Ethics review

Status: Approved
Approval date: 09/05/2006
Contact:

Results

• Results available: Yes
• Date Posted: 15/04/2016
• Date Completed: 11/07/2011
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-003413-32/results