E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
compensated advanced chronic liver disease |
enfermedad hepática crónica avanzada compensada |
|
E.1.1.1 | Medical condition in easily understood language |
chronic liver disease |
enfermedad hepática crónica |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001422 |
E.1.2 | Term | Advanced chronic liver disease |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
|
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 whether the oral administration of zinc acexamate (ACZ) at a dose of 600mg/day (equivalent to 100mg/day of elemental zinc) to patients with cACLD, improves your prognosis by reducing expected clinical events and the risk of suffering from them during during study follow-up. |
El objetivo principal de este ensayo clínico es evaluar si la administración oral de Acexamato de zinc (ACZ) a la dosis de 600mg/día (equivalente a 100 mg/día de zinc elemento) a pacientes con cACLD, mejora su pronóstico reduciendo los eventos clínicos esperables y el riesgo de padecerlos durante el seguimiento del estudio. |
|
E.2.2 | Secondary objectives of the trial |
To assess whether the administration of ACZ improves the risk of first decompensation and what type. To assess whether it reduces the overall risk of clinically significant portal hypertension [CSPH] estimated by the model described Assess whether it improves the risk of hepatocarcinoma. To study if it reduces the risk of bacterial infections. To assess whether it improves overall transplant-free survival. Assess whether it improves transplant-free survival in relation to liver-related deaths. Assess whether liver function improves as measured by the Child-Pugh score and the MELD scale. To assess whether the effects on the main variable or on each of the secondary variables separately, correlate with blood zinc levels during treatment. To evaluate the possible adverse effects of treatment with ACZ. |
Evaluar si la administración de ACZ mejora el riesgo de primera descompensación y que tipo. Evaluar si disminuye el riesgo global de hipertensión portal clínicamente significativa [CSPH] estimado por el modelo descrito Valorar si mejora el riesgo de hepatocarcinoma. Estudiar si disminuye el riesgo de infecciones bacterianas. Evaluar si mejora la supervivencia global libre de trasplante. Valorar si mejora la supervivencia libre de trasplante en relación a muertes de causa hepática. Valorar si mejora la función hepática medida por la puntuación de Child-Pugh y la escala MELD. Evaluar si los efectos sobre la variable principal o sobre cada una de las secundarias por separado, se correlacionan con los niveles de zinc en sangre durante el tratamiento. Evaluar los posibles efectos adversos al tratamiento con ACZ. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients of both sexes with cACLD diagnosed by hepatic stiffness by transition elastography >15 kPa. Age between 18 and 80 years, both inclusive. Absence of previous or current decompensation. In women of childbearing age, a possible pregnancy will be ruled out by means of a pregnancy test prior to the start of the study. Once the test has been carried out, the woman must use an effective contraceptive method during sexual intercourse to be maintained from the days prior to the start of treatment, and will continue to use them while the treatment is ongoing, as well as until a few days after finishing it. Sign the informed consent.
Notes: Patients with esophageal varices at baseline endoscopy should be treated prophylactically with beta-blockers (preferably carvedilol) and may be included if they meet the inclusion criteria. Patients who present or have a high probability of presenting CSPH may be treated with beta-blockers (carvedilol preferably). The presence of CSPH is defined as: - HVPH ≥ 10 mm Hg - Presence of collateral circulation in imaging tests - Liver stiffness by transition elastography ≥25 kPa. |
Pacientes de ambos sexos con cACLD diagnosticada por una rigidez hepática por elastografía de transición >15 kpa. Edad comprendida entre los 18 y los 80 años, ambos inclusive. Ausencia de descompensación previa o actual. En las mujeres en edad fértil se descartará un posible embarazo mediante una prueba de embarazo previa al inicio del estudio. Una vez realizada la prueba, la mujer deberá utilizar un método anticonceptivo eficaz en las relaciones sexuales (ver Anexo I) que mantenga en los días previos al inicio del tratamiento, y seguirá aplicándolos mientras dure el tratamiento, así como hasta unos días después de finalizarlo. Firmar el consentimiento informado.
Notas: Los pacientes que presenten varices esofágicas en la endoscopia basal deberán ser tratados profilácticamente con beta-bloqueantes (carvedilol preferentemente) y podrán ser incluidos, si cumplen los criterios de inclusión. Los pacientes que presenten o tengan alta probabilidad de presentar CSPH podrán ser tratados con beta-bloqueantes (carvedilol perferentemente). La presencia de CSPH queda definida como: - HVPH ≥ 10 mm Hg - Presencia de circulación colateral en las pruebas de imagen - Rigidez hepática por elastografía de transición ≥25 kPa. |
|
E.4 | Principal exclusion criteria |
History or current presence of hepatocarcinoma. Concomitant systemic disease, with low short-term prognosis for life. Pregnancy, breastfeeding, or refusal to use contraceptive measures whilst participating in the study. Patients with cACLD due to HBV on antiviral treatment and with cACLD due to HCV cured with antiviral treatment. |
Antecedentes o presencia actual de hepatocarcinoma. Enfermedad concomitante sistémica, con pronóstico de vida bajo a corto plazo. Embarazo, lactancia, o negativa a emplear medidas anticonceptivas durante su participación en el estudio. Pacientes con cACLD por VHB en tratamiento antiviral y con cACLD por VHC curados con tratamiento antiviral. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Occurrence of time-dependent clinical events during study follow-up, along with the distribution of CSPH risk estimated by the ANTICIPATE model. Clinical events are defined as the sum of: 1. Hepatic decompensation defined as the presence of clinical ascites, gastrointestinal bleeding due to portal hypertension, and hepatic encephalopathy. 2. Hepatocellular carcinoma. 3. Death from liver causes (considering non-hepatic death as a competitive risk). 4. Liver transplant. |
Aparición de eventos clínicos dependientes del tiempo, durante el seguimiento del estudio, junto con la distribución del riesgo de CSPH estimado por el modelo ANTICIPATE. Los eventos clínicos quedan definidos como la suma de: 1. Descompensación hepática definida como presencia de ascitis clínica, hemorragia gastrointestinal por hipertensión portal y encefalopatía hepática. 2. Carcinoma hepatocelular. 3. Muerte de causa hepática (considerando la muerte de causa no hepática como riesgo competitivo). 4. Trasplante hepático. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The clinical follow-up will be every 3 months during the first 2 years, and then every 6 months until the end of the stud. Specific tests will be every 12 months and routine tests every 6 months. |
El seguimiento clínico será cada 3 meses durante los 2 primeros años, y posteriormente cada 6 meses hasta al final del estudio. Las pruebas específicas serán cada 12 meses y las rutinarias cada 6 meses. |
|
E.5.2 | Secondary end point(s) |
The secondary variables will consist of the evolutionary development of each of the secondary objectives |
Las variables secundarias consistirán en el desarrollo evolutivo de cada uno de los objetivos secundarios |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The clinical follow-up will be every 3 months during the first 2 years, and then every 6 months until the end of the study. Specific tests will be every 12 months and routine tests every 6 months. |
El seguimiento clínico será cada 3 meses durante los 2 primeros años, y posteriormente cada 6 meses hasta al final del estudio. Las pruebas específicas serán cada 12 meses y las rutinarias cada 6 meses. |
|
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 | No |
E.8.1.4 | Double blind | Yes |
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 | 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 | 15 |
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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |