A 24-month, multi-center, randomized, open-label non-inferiority study of efficacy and safety comparing two exposures of concentration-controlled Certican with reduced Neoral versus 3.0 g MMF with standard dose Neoral in de novo heart transplant recipients

• Register: EUCTR
• Last refreshed on: 1 May 2012
• Main ID: EUCTR2005-003413-32-DE
• Date of registration: 17/07/2006
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 24-month, multi-center, randomized, open-label non-inferiority study of efficacy and safety comparing two exposures of concentration-controlled Certican with reduced Neoral versus 3.0 g MMF with standard dose Neoral in de novo heart transplant recipients
• Scientific title: A 24-month, multi-center, randomized, open-label non-inferiority study of efficacy and safety comparing two exposures of concentration-controlled Certican with reduced Neoral versus 3.0 g MMF with standard dose Neoral in de novo heart transplant recipients
• Date of first enrolment: 22/09/2006
• 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: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Austria, 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.
• Women of childbearing potential should have a negative serum or urine pregnancy
test with a sensitivity of at least 25 mIU/mL within 1 week prior to beginning
therapy. Females are eligible if they are postmenopausal for at least 24 months past
last natural menses. Study medication should not be administered until a negative
pregnancy test report is obtained. Two or more acceptable methods of contraception
should be started 1 month prior to beginning study drug unless abstinence is the
chosen method, during therapy, and for 3 months after stopping the study.
Abstinence is an allowed contraceptive method if in the judgment of the investigator the patient is reliably abstaining. Celibate members of religious orders (like nuns,
priests, etc...) will be considered in consultation with the local Novartis Medical
Advisor on a case by case basis. Although there may be local/ country specific
differences, acceptable forms of birth control include any two or more of the
following methods: surgical sterilization (e.g. bilateral tubal ligation, hysterectomy),
hormonal contraception (implantable, patch, oral), IUD and barrier methods (male
or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Periodic
abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and
withdrawal are not acceptable methods of contraception.

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/mm3 at the evaluation before randomization.
•Patients who are recipients of multiple solid organ ro tissues transplants or have previously received organ transplants.
•Patients who are recipients of ABO incompatible transplants
•Patients with clinically significant systemic infection at time of transplant or within 2 weeks prior to transplant
•Patients receiving investigational drug or who have been treated with a non-protocol immunosuppresive drug or treatment within 1 months prior to randomisation.
•Patients receiving induction therapy in non induction center
•Patients not receiving induction therapy in an induction center
•Induction therapy other than Simulect or thymoglobulin
•Patients at Simulect resp. thymoglobulin induction therapy receiving an induction therapy that is not Simulect rsp. thymoglobulin
•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 been tested positive for HIV or Hepatitis C or are positive for Hepatitis B surface AG. Laboratory results obtained within 6 months prior to study entry are acceptable; otherwise these tests should be performed within 1 week after randomisation
•Recipients of organs from donors who test positive for Hepatitis B surface AG or Hepatitis C
•Patients being treated with terfenadine, astemizole, or cisapride
•Patients with any past history (within the past 5 years) or present malignancy, whether or not there is evidence of local recurrence or metastases (other than excised non-melanoma skin lesions)
•Patients with a known hypersensitivity to drugs of this class.
•Patients with donor greater than 65 years and/or with known donor coronary or 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 by mouth (short-term NG administration allowed not longer than Day 5).
•Existence of any surgical or medical condition significantly altering ADME of study medication; and/or presence of severe diarrhea or active peptic ulcer.
•abnormal physical or laboratory findings of clinical significance with 2 weeks of randomisation interfering with the objectives of the study
•Femals of childbearing potential planning to become pregnant, being pregnant and/or lactating, unwilling to use effective means of contraception
•Females of childbearing potential who are planning to become pregnant, who are
pregnant and/or lactating, who are unwilling to use at least two effective means of
contraception.



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

Health Condition(s) or Problem(s) studied

de novo heart transplantation
MedDRA version: 8.1 Level: LLT Classification code 10019314 Term: Heart transplant

Intervention(s)

Trade Name: Certican 0,25 mg Tabletten
Product Name: Certican
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Trade Name: Certican 0,5 mg Tabletten
Product Name: Certican
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Trade Name: Certican 0,75 mg Tabletten
Product Name: Certican
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.75-

Trade Name: CellCept 500 mg Tabletten
Product Name: CellCept
Pharmaceutical Form: Tablet
INN or Proposed INN: Mycophenolate mofetil
CAS Number: 115007-34-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Sandimmun Optoral 10 mg Kapseln
Product Name: Sandimmun Optoral
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Ciclosporin
CAS Number: 59865-13-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Sandimmun Optoral 25 mg Kapseln
Product Name: Sandimmun Optoral
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Ciclosporin
CAS Number: 59865-13-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Sandimmun Optoral 50 mg Kapseln
Product Name: Sandimmun Optoral
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Ciclosporin
CAS Number: 59865-13-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Sandimmun Optoral 100 mg Kapseln
Product Name: Sandimmun Optoral
Pharmaceutical Form: Capsule, soft
INN or Propose

Primary Outcome(s)

Primary end point(s): The primary objective of the study is to show that Certican 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

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 Cerican 1.5 mg/d and those receiving MMF as measured by intravascular ultrasound (IVUS) at 12 months.

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 ID(s)

2005-003413-32-GB

CRAD001A2310