E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart transplantation or lung transplantation |
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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 |
The primary objective is to investigate whether initiation of everolimus together with reduction of calcineurin inhibitors (CNI) in maintenance heart or lung transplant patients with renal impairment will improve renal function. This will be assessed by comparing renal function assessed by measured glomerular filtration rate (mGFR) between the treatment groups, using the change from baseline to Month 12 of treatment. |
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E.2.2 | Secondary objectives of the trial |
To compare: • number and severity of treated biopsy proven acute rejections • number of treated acute rejections • patient and graft survival • slopes of reciprocal serum creatinine (1/Cr) and slope of change of calculated GFR levels over study duration • safety parameters (incidence of hypertension, hyperlipidemia, diabetes mellitus, anemia, thrombocytopenia, malignancies and infections) • number of patients in need of dialysis during the study • health economy data measured as average total days of hospitalization between the groups • number of treatment failures • intima media thickness changes of coronary artery by intravascular ultrasound • the incidence or worsening of bronchiolitis obliterans syndrome • changes in lung function (lung transplant recipients) • the incidence of major adverse cardiovascular events (heart transplant recipients) • left ventricular function (heart transplant recipients) |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Male or female patient at least 18 years of age. Patient who have undergone a heart or lung transplantation more than 12 months ago. Patient receiving Neoral® or Prograf®. Patients with a measured or calculated GFR > 20 and <70 mL/min /1,73m2, and in the opinion of the investigator have a deteriorating renal function.
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E.4 | Principal exclusion criteria |
Patient who is recipient of multiple organ transplants. Patient with measured or calculated GFR < 20 mL/min/1,73m2 or > 70 mL/min/1,73m2. Patient with a treated acute rejection episode within the last 3 months. Patient with a platelet count of < 50,000/mm3 or with a white blood cell count of ≤ 2,500/mm3 or with a hemoglobin value < 8 g/dL. Presence of severe hypercholesterolemia (≥ 8,0 mmol/L) or hypertriglyceridemia (≥ 6,0 mmol/L) despite conventional lipid lowering treatment. Patient being currently treated or who has been treated with a mTOR inhibitor. Patient who had received an investigational drug within 4 weeks. Patient who is human immunodeficiency virus positive or who has a current severe systemic infection according to the investigator judgment requiring continued therapy. Present use of any other immunosuppressive drugs than Neoral®/Prograf® , MPA/AZA and steroids. Patients with a known hypersensitivity to drugs similar to everolimus.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective will be assessed by comparing renal function assessed by measured glomerular filtration rate (mGFR), using the change from baseline to month 12 of treatment, between the 2 groups of patients: • Group A: current immunosuppressive regimen continuation (Control arm) • Group B: initiation of everolimus (3-8 ng/mL) with reduction of CNI (Test arm) That is, the primary objective is to show either Group B will be superior to control Group A with respect to mean mGFR change from baseline to month 12 of treatment |
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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 | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Current Immunosuppressive regimen continuation |
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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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |