E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
After kidney transplantation all patients need to use immunosuppression to prevent rejection |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
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 |
To evaluate if steroid-free immunosuppressive protocol, based on thymoglobulin induction, reduces the incidence of new onset diabetes after transplantation |
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E.2.2 | Secondary objectives of the trial |
The composite measure of freedom from acute rejection (AR), graft survival, and patient survival at 12 and 24 months after transplantation. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients receiving a first or second single kidney transplant from a deceased or a living donor.
2. Female or male aged above 18 years.
3. Patients considered for a standard immunosuppressive protocol.
4. Patients capable of giving written informed consent for participation in the study for 24 months.
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E.4 | Principal exclusion criteria |
1. Patients with known diabetes mellitus or plasma glucose >11.1 mmol/l at admission
2. Patients receiving steroids at the time of transplantation or likely to need steroids after transplantation
3. Recipients of multiorgan transplants, and or previously transplanted with any other organ than kidney
4. Patients with CDC-PRA > 25 % in most recent test or for any other reason considered to be of a high risk for rejection which requires an enhanced immunosuppression.
5. Patients receiving a renal transplant from a HLA-identical sibling
6. Patients with hypersensitivity to, or other reasons to not be able to take the immunosuppressive drugs used in the study
7. Patients who are recipients of ABO-incompatible transplants
8. Patients who are unlikely to comply with the study requirements
9. Patients, and/or those receiving organs from donors, who are positive for HIV, Hepatitis B surface antigen or Hepatitis C virus.
10. Females of childbearing potential, who are, or are planning to be, pregnant, and/or are unwilling to use effective means of contraception.
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E.5 End points |
E.5.1 | Primary end point(s) |
Cumulative incidence of one of the following:
≥2 FPG ≥7, 0 mmol/l ≥ 30 days apart or
2-h Plasma Glucose ≥11,1 mmol/l in the OGTT≥ 30 days apart or
Oral hypoglycemic ≥30 consecutive days or
Insulin ≥30 consecutive days
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• The cumulative incidence of NODAT (new onset of diabetes after transplantation) 3, 6 and 24 months after transplantation as defined above.
• Use of antidiabetic medication at 3, 6, 12 and 24 months.
• The composite measure of freedom from acute rejection (AR), graft survival, and patient survival at 12 and 24 months after transplantation. The diagnosis of AR will be based on histological biopsy confirmation using the Banff Working Classification of Kidney Transplant Pathology (Sis, 2010). Per protocol, graft loss was defined as the occurrence of transplant nephrectomy or a return to permanent maintenance dialysis for more than 8 weeks post-transplant.
• The incidence of antibody-mediated rejection using the Banff Working Classification (Sis, 2010) and of HLA-donor specific antibodies.
• Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance, at 12 and 24 months,
• The incidence of both acute and chronic changes, analyzed by protocol biopsies at transplantation and after 12 months, evaluated by the Banff system (Sis, 2010).
• Incidence of hypertension measured in a standardized way at 3 and 12 24 months
• Number of antihypertensive drugs at 3,12 and 24 months
• Number of lipid lowering drugs at 12 and 24 months
• Incidence of cardiovascular complications and events
• Incidence of malignancy
• Incidence of infections
• Safety and tolerability
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | No |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |