E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Compensated cirrhosis |
Cirrosis compensada |
|
E.1.1.1 | Medical condition in easily understood language |
Compensated cirrhosis |
Cirrosis compensada |
|
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 | 10064844 |
E.1.2 | Term | Compensated cirrhosis |
E.1.2 | System Organ Class | 100000004871 |
|
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 assess whether the oral administration of zinc acexamate (ACZ) at a dose of 600mg / day (equivalent to 100mg / day of elemental zinc) to patients with compensated liver cirrhosis reduces the expected clinical events during the study follow-up period |
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 cirrosis hepática compensada, reduce los eventos clínicos esperables durante el periodo de seguimiento del estudio |
|
E.2.2 | Secondary objectives of the trial |
Evaluate if the administration of ACZ improves the risk of first decompensation and what type. Assess if the risk of hepatocarcinoma improves Study if it reduces the risk of bacterial infections. Evaluate if it improves overall transplant-free survival. Assess if it improves transplant-free survival in relation to liver-related deaths. Evaluate if it decreases hospital admissions. Assess if liver function improves as measured by the Child-Pugh score and the MELD scale. To assess if the effects on the main variable or on each of the secondary variables separately, correlate with blood zinc levels during treatment. To assess the possible adverse effects of ACZ treatment |
Evaluar si la administración de ACZ mejora el riesgo de primera descompensación y que tipo. 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. Evaluar si disminuye los ingresos hospitalarios. 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 liver cirrhosis diagnosed by clinical, analytical (biochemical) and imaging criteria (ultrasonography, liver elastography, computerized tomography). Age between 18 and 80 years, both inclusive. Absence of previous or current decompensation. Child-Pugh score greater than or equal to 6 points. Sign the informed consent.
Note: Patients with esophageal varices at baseline endoscopy should be treated prophylactically with beta-blockers and may be included, if they meet the inclusion criteria. Patients with HBV cirrhosis receiving antiviral treatment, and HCV patients cured with antiviral treatment, may be included in the trial, if they meet the inclusion criteria. |
Pacientes de ambos sexos con cirrosis hepática diagnosticada por criterios clínicos, analíticos (bioquímicos) y de imagen (ultrasonografía, elastografía hepática, tomografía computerizada). Edad comprendida entre los 18 y los 80 años, ambos inclusive. Ausencia de descompensación previa o actual. Puntuación de Child-Pugh mayor o igual a 6 puntos. Firmar el consentimiento informado.
Nota: Los pacientes que presenten varices esofágicas en la endoscopia basal deberán ser tratados profilácticamente con beta-bloqueantes y podrán ser incluidos, si cumplen los criterios de inclusión. Los pacientes con cirrosis por VHB en tratamiento con antivirales, y los pacientes con VHC curados con tratamiento antiviral, podrán ser incluidos en el ensayo, si cumplen los criterios de inclusión. |
|
E.4 | Principal exclusion criteria |
History or current presence of hepatocarcinoma. Concomitant systemic disease, with a poor short-term prognosis for life. Pregnancy and breastfeeding. Patients with untreated HBV cirrhosis and uncured HCV cirrhosis. |
Antecedentes o presencia actual de hepatocarcinoma. Enfermedad concomitante sistémica, con pronóstico de vida bajo a corto plazo. Embarazo y lactancia. Pacientes con cirrosis por VHB no tratados y con cirrosis por VHC no curados. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Appearance of time-dependent clinical events during study follow-up. These 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 any cause (considering non-hepatic death as a competitive risk). |
Aparición de eventos clínicos dependientes del tiempo, durante el seguimiento del estudio. Estos 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 cualquier causa (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 study (42 months). 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 (42 meses). 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 (42 months). 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 (42 meses). 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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |