E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
kidney transplantation |
nier transplantatie |
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E.1.1.1 | Medical condition in easily understood language |
kidney transplantation |
nier transplantatie |
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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 minimize the occurrence of sub-therapeutic and supra-therapeutic C0 of tacrolimus on day 3 after transplantation by basing the starting dose of tacrolimus on a dosing algorithm, rather than the standard bodyweight-only-based approach. More specifically, we will investigate whether a tacrolimus starting dose based on the algorithm will lead to a sufficient percentage of patients being within the tacrolimus target C0 on day 3 after transplantation, w.r.t. the percentage found in one historic control group of patients who have received a standard starting dose of tacrolimus; in that case a randomized trial might be an option. |
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E.2.2 | Secondary objectives of the trial |
We will also describe:
• The percentage of patients with extremely high or low tacrolimus C0 on day 3 after transplantation;
• The percentage of patients within the target C0 on days 5, 7 and 10 after transplantation;
• The time to achievement of tacrolimus target C0;
• Incidence of BPAR and (serious) adverse events within the first 30 days after transplantation;
• The relationship between the intracellular tacrolimus concentration in PBMCs and the whole blood concentration
and compare them with those observed in the historic control group which could add to the decision to perform a randomized trial.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 years old
• Patients receiving a kidney from a living donor (related or unrelated)
• Patients receiving a kidney from a blood group AB0-compatible donor
• Patients receiving a kidney form an HLA-compatible donor (non-desensitized patients)
• Patients who will receive tacrolimus as part of the initial immunosuppressive therapy
• Signed written informed consent |
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E.4 | Principal exclusion criteria |
• Recipients of a non-renal organ transplant at the same occasion
• Recipients receiving immunosuppressive therapy (except steroid treatment) within the preceding 28 days.
• Recipients using medication known to have a pharmacokinetic interaction with tacrolimus |
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E.5 End points |
E.5.1 | Primary end point(s) |
The main study endpoint of the study is the proportion of patients reaching the target C0 (7.5-12.5 ng/mL) on day 3 after transplantation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 days after transplantation |
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E.5.2 | Secondary end point(s) |
• The proportion of patients reaching the target C0 (7.5-12.5 ng/mL) on day 5, 7 and 10.
• The proportion of patients with markedly supra- (>20 ng/mL) or sub-therapeutic (<5 ng/mL) tacrolimus C0 on day 3 after transplantation.
• The time to reach the target C0 (7.5-12.5 ng/mL).
• Incidence of BPAR and (serious) adverse events within the first 30 days after transplantation.
• The relationship between the intracellular tacrolimus concentration in PBMCs and the whole blood concentration |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3, 5, 7 and 10 days after transplantation.
The incidence of BPAR will be evaluated the first 30 days after transplantation |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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) | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |