| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Liver transplantation. |
| Transplante hepático. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients who will undergo liver transplantation. |
| Pacientes que se someterán a un trasplante de hígado. |
|
| E.1.1.2 | Therapeutic area | Not possible to specify |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10024714 |
| E.1.2 | Term | Liver transplant |
| E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10024716 |
| E.1.2 | Term | Liver transplantation |
| E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10050434 |
| E.1.2 | Term | Prophylaxis against liver transplant rejection |
| E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
| 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 the area under the curve (AUC) GPT (ALT) after transplantation during 7 days. |
| Evaluar el área bajo la curva (AUC) GPT (ALT) después del trasplante durante 7 días. |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the absolute peak LDH within 7 days after transplantation
2. To evaluate the initial poor function, defined as one or more of the following laboratory parameters: bilirubin ≥ 10 mg/dl on Day 7 after the surgery; INR ≥ 1.6 on Day 7 after the surgery; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2000 IU/L within the first 7 days after the surgery (Olthoff criteria)
3. To evaluate the moment (day) of peak GPT and peak LDH
4. To evaluate the serum bilirubin, GOT, GPT, LDH, total albumin and PT at 3 months and 6 months
5. To evaluate the biliary complications: number of episodes of cholestasis, therapy for cholangitis, episodes of biliary leakage and intrahepatic and/or extrahepatic biliary strictures.
6. To compare liver transplants with extended criteria donors (ECD) and DCD donors with both preservation solutions. |
1. Evaluar el pico absoluto de LDH dentro de los 7 días posteriores al trasplante.
2. Evaluar la mala función inicial, definida como uno o más de los siguientes parámetros de laboratorio: bilirrubina ≥ 10 mg / dl el día 7 después de la cirugía; INR ≥ 1,6 el día 7 después de la cirugía; alanina aminotransferasa (ALT) o aspartato aminotransferasa (AST)> 2000 UI / L dentro de los primeros 7 días después de la cirugía (criterios de Olthoff)
3. Evaluar el momento (día) de pico de GPT y pico de LDH.
4. Evaluar la bilirrubina sérica, GOT, GPT, LDH, albúmina total y PT a los 3 y 6 meses
5. Evaluar las complicaciones biliares: número de episodios de colestasis, tratamiento de colangitis, episodios de fuga biliar y estenosis biliares intrahepáticas y / o extrahepáticas.
6. Comparar trasplantes de hígado con donantes de criterios extendidos (ECD) y donantes DCD con ambas soluciones de conservación. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Recipients awaiting their first transplant
2. Recipients ≥18 years
3. Recipient’s signed informed consent of data use and protection before the transplantation
4. Full organ transplantation |
1. Receptores en espera de su primer trasplante
2. Destinatarios ≥18 años
3. Consentimiento informado firmado del destinatario sobre el uso y la protección de los datos antes del trasplante
4. Trasplante completo de órganos |
|
| E.4 | Principal exclusion criteria |
1. Pregnant or lactating patients
2. Recipients participating in any interventional study (e.g. another study involving compound/interventions aimed at the reduction of preservation and/or ischemia/reperfusion injury)
3. All combined allocations other than pancreas and kidney
4. High urgency patients |
1. Pacientes embarazadas o lactantes
2. Receptores que participan en cualquier estudio de intervención (por ejemplo, otro estudio que involucre compuestos / intervenciones dirigidas a la reducción de la preservación y / o lesión por isquemia / reperfusión)
3. Todas las asignaciones combinadas distintas del páncreas y el riñón
4. Pacientes de alta urgencia |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Area under the curve (AUC) GPT (ALT) after transplantation during 7 days: with each liver transplant patient enrolled in the study, GPT will be measured once per day during the first 7 days, according to the standard practice of the center laboratory. Area under the curve will be analysed for this variable comparing Custodiol and Custodiol-N groups. |
| Área bajo la curva (AUC) GPT (ALT) después del trasplante durante 7 días: con cada paciente de trasplante de hígado inscrito en el estudio, la GPT se medirá una vez al día durante el primeros 7 días, de acuerdo con la práctica estándar del laboratorio del centro. Se analizará el área bajo la curva para esta variable comparando los grupos Custodiol y Custodiol-N. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| After transplantation during 7 days. |
| Después del trasplante durante 7 días. |
|
| E.5.2 | Secondary end point(s) |
1. Absolute peak LDH within 7 days after transplantation: the highest peak of lactate-dehydrogenase within 7 days after transplantation according to the practice of the site laboratory.
2. Olthoff criteria: bilirubin, international normalized ratio of prothrombin (INR), ALT/AST will be measured according to the practice of the site laboratory. The Olthoff criteria will be applied to evaluate initial poor function when one or more of the following parameters would be present:
• Bilirubin ≥ 10 mg/dl on Day 7 after the surgery
• INR ≥ 1.6 on Day 7 after the surgery
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2000 IU/L within the first 7 days after the surgery
3. MEAF score (Model for early allograft dysfunction)
4. Evaluation of the moment (day) of peak GPT and peak LDH: the highest daily peak GPT and peak LDH will be evaluated for comparisons between groups.
5. Evaluation of the serum bilirubin, GOT, GPT, LDH, total albumin and PT at 3 months and 6 months: these parameters will be measured at 3 months and 6 months after liver transplantation according to the references values of the site laboratory.
6. Number of episodes of cholestasis.
7. Therapy for cholangitis.
8. Episodes of biliary leakage and intrahepatic and/or extrahepatic biliary strictures.
9. Comparison in Extended Criteria Donors: the influence of Custodiol-N in liver transplants with ECD and DCD donors will be compared. ECD donors are defined as high risk donors with a donor risk index (DRI) higher than 1.7.
10. Comparison in DCD donors: DCD donors are defined as donation after circulatory death donors and will be compared in liver transplants with Custodiol and Custodiol-N. |
1. Pico absoluto de LDH dentro de los 7 días posteriores al trasplante: el pico más alto de lactato-deshidrogenasa dentro de los 7 días posteriores al trasplante según la práctica del laboratorio del centro.
2. Criterios de Olthoff: bilirrubina, índice internacional normalizado de protrombina (INR), ALT / AST se medirá de acuerdo con la práctica del laboratorio del sitio. Los criterios de Olthoff se aplicarán para evaluar la función deficiente inicial cuando uno o más de los siguientes parámetros estarían presentes:
• Bilirrubina ≥ 10 mg / dl el día 7 después de la cirugía
• INR ≥ 1,6 el día 7 después de la cirugía
• Alanina aminotransferasa (ALT) o aspartato aminotransferasa (AST)> 2000 UI / L dentro de los primeros 7 días después de la cirugía
3. Puntaje MEAF (modelo para la disfunción temprana del aloinjerto)
4. Evaluación del momento (día) del pico de GPT y del pico de LDH: se evaluarán el pico diario más alto de GPT y el pico de LDH para realizar comparaciones entre los grupos.
5. Evaluación de la bilirrubina sérica, GOT, GPT, LDH, albúmina total y PT a los 3 meses y 6 meses: estos parámetros se medirán a los 3 meses y 6 meses después del trasplante hepático según los valores de referencia del laboratorio del centro.
6. Número de episodios de colestasis.
7. Terapia de la colangitis.
8. Episodios de fuga biliar y estenosis biliares intrahepáticas y / o extrahepáticas.
9. Comparación en donantes de criterios extendidos: se comparará la influencia de Custodiol-N en trasplantes de hígado con donantes ECD y DCD. Los donantes de ECD se definen como donantes de alto riesgo con un índice de riesgo del donante (DRI) superior a 1,7.
10. Comparación en donantes DCD: Los donantes DCD se definen como donación tras muerte circulatoria y se compararán en trasplantes de hígado con Custodiol y Custodiol-N. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 7 days, 1 month, 3 months and 6 months after transplantation. |
| 7 días, 1 mes, 3 meses y 6 meses después del trasplante. |
|
| 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 | No |
| E.8.1.3 | Single blind | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 5 |
| 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
|
| LVLS. |
| Última visita del último paciente. |
|
| 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 | 33 |
| E.8.9.1 | In the Member State concerned days | |
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