E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with renal dysfunction undergoing liver transplantation |
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E.1.1.1 | Medical condition in easily understood language |
Patients with renal dysfunction undergoing liver transplantation |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019846 |
E.1.2 | Term | Hepatorenal syndrome |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038474 |
E.1.2 | Term | Renal insufficiency |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024678 |
E.1.2 | Term | Liver failure |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024667 |
E.1.2 | Term | Liver cirrhosis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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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 |
The objective of the study is to evaluate a de novo calcineurin-inhibitor (CNI)-free immunosuppressive regimen based on induction therapy with anti-CD25 monoclonal anti- body (basiliximab), mycophenolic acid (MPA), and mTOR-inhibition with everolimus to determine its safety and to investigate the preliminary efficacy in patients with impaired renal function at the time-point of liver transplantation (LT) with regards to the incidence of steroid-resistant acute rejection within the first 30 days after liver transplantation.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess liver and kidney function in patients receiving the proposed reno-protective immunosuppressive regimen for up to one year after liver transplantation.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients undergoing primary liver transplantation. 2. Patients older than 18 years. 3. Patients with a hepatorenal syndrome 4. Female patients of childbearing potential willing to perform a highly effective contraception during the study and 12 weeks after conclusion of study participation. 5. eGFR < 50 ml/min at the time point of transplantation 6. Serum creatinine levels > 1.5 mg/dL at the time-point of transplantation
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E.4 | Principal exclusion criteria |
1. Patients with pre-transplant renal replacement therapy > 14 days. 2. Patients with a reason for renal impairment other than a hepatorenal syndrome. 3. Patients with a known hypersensitivity to mTOR-inhibitors. 4. Patients with a known hypersensitivity to mycophenolate acid. 5. Patients with a known hypersensitivity to anti-CD25-monoclonal antibodies. 6. Patients with platelets < 50.000/nl prior to initiation of therapy with mTOR inhibition. 7. Patients with triglycerides > 350 mg/dl and cholesterol > 300 mg/dl refractory to optimal medical treatment prior to initiation of therapy with mTOR inhibition. 8. Severe systemic infections and wound-healing disturbances. 9. Multiple organ graft recipients. 10. Patients with signs of a hepatic artery stenosis directly prior to initiation of therapy with Sirolimus. 11. Pregnant women will not be included in the study. 12. Patients with a psychological, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule. 13. Patients under guardianship (e. g. individuals who are not able to freely give their informed consent).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint in our study is the time-point of biopsy proven steroid resistant acute rejection within the first 30 days after LT.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
within the first 30 days after LT |
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E.5.2 | Secondary end point(s) |
Incidence of acute rejections within 30 days and 3, 6 and 12 months after LT Number of acute rejections per patient Timepoint of acute rejection´s after LT Improvement and deteriration of renal function at 1, 3, 6 and 12 months in comparison to pretransplant renal function; estimated by estimated glomerular filtration rate (eGFR) calculated by MDRDformula Number of patients requiring renal replacement therapy Duration of renal replacement therapy Liver allograft function Infectious complications Treatment failure, defined as reintroduction of CNI Hemato-lymphatic side effects Incidence of hepatic artery stenoses Wound-healing disturbances Mortality
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 3 |
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 | 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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Trial is ended at the completion of follow-up of the last patient included in 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 | 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 | 0 |
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 |