E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This study is designed to evaluate whether Certican® initiation, together with discontinuation of calcineurin inhibitors (CNIs) will have a beneficial effect on the renal function in maintenance heart transplant recipients with CNI-related renal impairment, while maintaining efficacy. |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Change in renal function assessed by mGFR from baseline to month 12 after randomization between the group of patients receiving Certican® and the control group with unchanged CNI-based immunosuppressive treatment. |
|
E.2.2 | Secondary objectives of the trial |
• Incidence of treated acute rejection episodes • Proteinuria (protein/creatinine ratio, measured in first morning urine sample) • Incidence of graft loss/retransplantation • Patient survival • Ultrasound left ventricular ejection fraction • Incidence of MACEs. MACEs include: acute myocardial infarction, congestive heart failure, percutaneous coronary intervention (PCI), automatic implanted cardiac defibrillator (AICD), coronary artery bypass graft surgery (CABG), cerebral vascular accident, and peripheral vascular disease. • Calculated GFR (cGFR n-MDRD formula) change from baseline. • Ambulatory 24h blood pressure monitoring • Safety parameters including: hypertension, diabetes mellitus, hyperlipidemia, anemia, infections and malignancies • Incidence of discontinuations, AEs and SAEs
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female over 18 years old • Patients who have undergone a heart transplantation at least 12 months ago • Patients with a calculated GFR (MDRD formula) ≤ 60 ml/min and ≥ 30 ml/min/1.73m2 (CKD stage 3) • Patients who are willing and capable to participate in the study for 12 months and who have given written informed consent. • Females capable of becoming pregnant must have a negative pregnancy test within 7 days prior to randomization and are required to practice a medically approved method of birth control for the duration of the study.
|
|
E.4 | Principal exclusion criteria |
• Dialysed patients • Patients with any treated acute rejection within 6 months prior to randomization • Patients with an identifiable cause of renal dysfunction other than CNI toxicity • Patients with platelet count ≤ 75.000/mm3 or white blood cell count ≤ 2.500/mm3 or hemoglobin value ≤ 8 g/dL • Patients with proteinuria ≥ 0.8 g/24h • Presence of a severe hypercholesterolemia (total cholesterol 9 mmol/l; 350mg/dl) or hypertriglyceridemia ( 8.5 mmol/l, 750 mg/dl) despite lipid lowering therapy • Patients with a current severe systemic infection • Patients with any history(within the past 5 years) or currently suffering from a malignancy, with an expected life-span of less than 2 years • Patients currently being treated with a mTOR inhibitor • Patients with a known intolerance or hypersensitivity to Certican® (everolimus) or similar drugs. • Severe hepatic disorders • Patients suffering from chronic hepatitis C (PCR positive) or who are HIV- or HBsAg-positive. The result of a laboratory test performed within the 6 months preceding the inclusion must be available. • Patients with a significant mental illness, which in the opinion of the investigator may interfere with patients’ ability to comply with the protocol. • Women who are pregnant or breastfeeding • Patients who have received an investigational drug within 4 weeks prior to study enrolment
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Change in renal function assessed by mGFR from baseline to month 12 after randomization between the group of patients receiving Certican® and the control group with unchanged CNI-based immunosuppressive treatment. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |