E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Biliary strictures after orthotopic liver transplantation caused by microthrombi in the donorliver during procurement |
Het voorkomen van galwegstricturen na transplantatie die veroorzaakt worden door microhthrombi in de donorlever. |
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E.1.1.1 | Medical condition in easily understood language |
Narrowing of the biliary tree after liver transplantation |
Het voorkomen van vernauwingen van de galwegen door donorlever te spoelen met een stolseloplossend medicijn |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
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 |
Prevention of biliary strictures after liver transplantation |
Voorkoming van galwegstricturen na levertransplantatie |
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E.2.2 | Secondary objectives of the trial |
• Graft survival • Patient survival • Number of graft failures due to biliary strictures
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• Transplantaat overleving • Patient overleving • Het aantal leverfalen door galwegstricturen
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Recipient inclusion criteria
- All patients who are eligible for liver transplantation
Donor inclusion criteria
- Donors from donation after cardiac death (DCD)
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Ontvanger inclusie criteria
- Alle patiënten die in aanmerking komen voor levertransplantatie
Donor inclusie criteria
- Donor lever afkomstig van donoren na hartstilstand
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E.4 | Principal exclusion criteria |
Patients eligible for liver transplantation younger than <18 Pregnant women |
Patienten die aanmerking komen voor levertransplantatie jonger dan 18 jaar Zwangere vrouwen |
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E.5 End points |
E.5.1 | Primary end point(s) |
The incidence (number) of biliary strictures after liver transplantation |
Het aantal galwegstricturen na levertransplantatie |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) On indication due to clinical symptoms 2) Evaluation using MRI of the biliary tree 1 year after liver transplantation |
1) Op indicatie bij klinische symptomen 2) Evaluatie van de galboom 1 jaar na levertransplantatie |
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E.5.2 | Secondary end point(s) |
1) Graft survival 2) Patient survival 3) Number of graft failures due to biliary strictures 4) Number of ERCPs, PTCs and surgical interventions performed to treat NAS in the first year 5) Number of hospitalizations and time of hospitalization 6) Number of admission days to the Intensive Care Unit (ICU) 7) Number of episodes of cholangitis 8) Adverse events (AE) and serious adverse events (SAE) 9) Ischemia times and relation to NAS 10)Transaminase peaks (ALAT/ASAT, bilirubin) 11)Peri-operative blood loss 12)Clotting, fibinolysis and remnants of t-PA in the recipients plasma 13)Primary non-function 14)Hepatic artery thrombosis (HAT) 15)Retransplantations due to biliary strictures 16)1-week liver biopsy for evaluation of ischemia/reperfusion damage |
1) Transplantaat overleving 2) Patient overleving 3) Aantal leverfalen door galwegstricturen 4) Aantal ERCPs, PTCs en chirurgische interventies om galwegstricturen te behandelen binnen 1 jaar 5) Aantal ziekenhuisopnames en aantal dagen van opname 6) Aantal opnamedagen op de Intensive Care Unit (ICU) 7) Aantal cholangitiden 8) Adverse events (AE) en serious adverse events (SAE) 9) Ischemie tijden 10) Transaminase pieken(ALAT/ASAT, bilirubin) 11) Peri-operatief bloedverlies 12) Restanten van t-PA activiteit in het plasma van de ontvanger 13) Primaire non-functie (PNF) 14) Arteria Hepatica Trombose (HAT) 15) Retransplantaties door galwegstricturen 16) Leverbiopt na 1 week ter evaluatie van de ischemie-reperfusieschade |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) On indication (retransplantation) 2) On indication 3) On indication (clinical symptoms) within 1 year 4) On indication (clinical symptoms) within 1 year 5) On indication (clinical symptoms) within 1 year 6) On indication (clinical symptoms) within 1 year 7) On indication (clinical symptoms) within 1 year 8) On indication (clinical symptoms) within 1 year 9) pre-operatively 10) 1week post transplantation 11) per-operatively 12) per-operatively 13) On indication (clinical symptoms) within 1 year 14) On indication (clinical symptoms) within 1 year 15) On indication (clinical symptoms) within 1 year 16) 1 week post-transplantation |
1) Op indicatie (retransplantatie) 2) Op indicatie 3) Op indicatie (klinische symptomen) binnen 1 jaar 4) Op indicatie (klinische symptomen) binnen 1 jaar 5) Op indicatie (klinische symptomen) binnen 1 jaar 6) Op indicatie (klinische symptomen) binnen 1 jaar 7) Op indicatie (klinische symptomen) binnen 1 jaar 8) Op indicatie (klinische symptomen) binnen 1 jaar 9) pre-operatief 10) 1week post transplantatie 11) per-operatief 12) per-operatief 13) Op indicatie (klinische symptomen) binnen 1 jaar 14) Op indicatie (klinische symptomen) binnen 1 jaar 15) Op indicatie (klinische symptomen) binnen 1 jaar 16) 1 week post-transplantatie |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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
| 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 | 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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The end of the trial will be at when the total number of patients are included and the last patient has 1 year of follow-upm. An interim-analysis will be performed upon 70% inclusion fraction to study efficacy. |
De studie zal eindigen als de laatste patient 1 jaar follow-up heeft gehad. Er zal tevens een interim-analyse plaatsvinden (70% inclusiefractie) voor superioriteits of futiliteits analyse. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |