E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019314 |
E.1.2 | Term | Heart transplant |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
To compare the efficacy between treatment regimes by assessing the difference in renal function evaluated by measured glomerular filtration rate (mGFR) 12 months after heart transplantation (HTX). |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy between treatment regimes by assessing the difference in
•Progression of chronic allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS) examination
•Renal function; change of GFR from visit 5 (week 7-11) to Month 12
•Renal function; cGFR (MDRD formula)at each follow-up visit
•Number of rejections
•Occurrence of treatment failures up to or at 12 months
•Development and magnitude of proteinuria
•Lipid profile at 12 months
•Quality of Life assessed by SF-36, EQ-5D and Becks
•Hemodynamic variables
•Left ventricular function
•Optional: Working capacity (Peak Oxygen uptake at week 7 and month 12)
•Metabolic parameters
•Inflammatory variables
•Safety and tolerability
•Optional: measurements of microvascular circulation in connection to the IVUS examinations
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be fulfilled at the time of transplantation and before entering period 1 of the study
- Male or female cardiac recipients 18-70 years of age undergoing primary heart transplantation. The graft must be functional at the time of randomization.
- Patient willing and capable of giving written informed consent for study participation and anticipated to be able to participate in the study for 12 months
- Patients received induction therapy with ATG (Thymoglobulin)
At time of entering period 2:
- Patients completed period 1 on the maintained immunosuppressive regimen they were randomized to within the target doses and levels specified for each group. |
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E.4 | Principal exclusion criteria |
To be fulfilled at the time of transplantation and before entering period 1 of the study
1.Recipient of multi-organ transplants or previously transplanted organs
2.Patients with donor greater than 70 years
3.Donor heart cold ischemic time > 6 hours.
4.Patients who are recipients of ABO incompatible transplants
5.Patients with platelet count < 50,000/mm3 at the evaluation before transplantation
6.Patient who have received an unlicensed drug or therapy within one month prior to study entry or if such therapy is to be instituted post-transplantation
7.Patient with a known hypersensitivity to cyclosporine
8.Patient with a current severe systemic infection
9.Patient unable to participate in the study for the full 12-month period
10.Presence of severe hypercholesterolemia (≥ 350 mg/dL; ≥ 9 mmol/L) or hypertriglyceridemia (≥ 750 mg/dL; ≥ 8.5 mmol/L)
11.Patients with any past (within the past 5 years) or present malignancy (other than excised basal cell carcinoma)
12.Females capable of becoming pregnant must have a negative pregnancy test prior to randomization and are required to practice a medically approved method of birth control for the duration of the study and a period of 8 weeks following discontinuation of study medication, even where there has been a history of infertility.
13.Patients with HIV, hepatitis B or C
At time of entering period 2:
1. Graft loss
2.Patients with ongoing treatment for rejection
3. Patients that have experienced a biopsy proven ISHLT grade 3R rejection or two or more grade 2R rejections during period 1
4. Patients who have experienced a humoral (antibody mediated) rejection with a hemodynamic compromise during period 1).
5.Patients with a hemoglobin count < 8,0 g/l (5.0 mmol/l); and/or a platelet count < 50 x 109/l and/or white blood cell count < 2.5 x 109/l)
6.Patients with total cholesterol (TC) >9 mmol/l and or triglycerides (TG) >6 mmol/l despite lipid lowering treatment
7.Patients with a spot urinary protein/creatinine or albumin/creatinine ratio > 100 mg/mmol
8.Patients with ongoing wound healing problems or other severe surgical complication in the opinion of the investigator
9.Patient with a current clinically severe systemic infection
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E.5 End points |
E.5.1 | Primary end point(s) |
•Measured Glomerular Filtration Rate (mGFR),Cr-EDTA clearance at week 7-11 and at 12 months
•Development of CAV : Intravascular Ultrasound (IVUS) and Virtual Histology (VH)
•Number of rejections
•Number of treatment failures
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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 | 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 | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 2 |