Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Hospital General Universitario Gregorio Marañon | OTHER |
| Hospital Vall d'Hebron | OTHER |
| Puerta de Hierro University Hospital | OTHER |
| Hospital Clinic of Barcelona |
Not provided
Not provided
Not provided
Zinc homeostasis could play a role in advanced chronic liver disease (cACLD) and its supplementation has been linked with improvement in liver function, decrease of hepatic complications and reduction in hepatocellular carcinoma (HCC) incidence. cACLD encompasses a heterogeneous group of patients with a variable risk of clinically significant portal hypertension (CSPH) and clinical events. The ANTICIPATE model is a validated model for stratifying these risks. Our aim is to demonstrate that the administration of zinc can reduce the rate and risk of presenting clinical events (first decompensation, HCC, death and liver transplantation). This study protocol describes an ongoing phase III, national, multicentre, randomized, double-blind clinical trial that will enroll 300 patients to receive either the trial treatment (zinc acexamate) or placebo. An inclusion period of 42 months is planned, with a minimal duration of follow up of 2 years. Our principal hypothesis is that zinc could modify the natural history of cACLD patients, with an overall improvement in prognosis
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zinc Acexamate | Experimental | The experimental group will receive ACZ at a daily dose of 600 mg, equivalent to 100mg of elemental zinc (one hard gelatin capsule of 300 mg of ACZ twice a day). Treatment will be stopped when the patient presents any of the events that define the main endpoint of the study. |
|
| Placebo | Placebo Comparator | The control group will receive twice a day orally hard gelatin capsules, identical to those of ACZ, in color, weight and nature, but containing an inert preparation (isomaltose). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zinc Acexamate | Drug | The experimental group will receive ACZ at a daily dose of 600 mg, equivalent to 100mg of elemental zinc (one hard gelatin capsule of 300 mg of ACZ twice a day). Treatment will be stopped when the patient presents any of the events that define the main endpoint of the study. The control group will receive twice a day orally hard gelatin capsules, identical to those of ACZ, in color, weight and nature, but containing an inert preparation (isomaltose). |
| Measure | Description | Time Frame |
|---|---|---|
| Values 1-6. Ordinal scale to assess efficacy of the intervention. | Ordinal scale to assess efficacy of the intervention, with expected distribution of patients on each study arm at the 2-year mark, based on an effect size of an OR of 0.55.The most severe category (Value 6) will be the development of clinical events:First decompensation,hepatocellular carcinoma, liver related-death (non-liver-related deaths as competing events), and liver transplantation.Those patients free of a liver-related event at 2 years,will be classified according to the risk of CSPH (ANTICIPATE model value), distributing patients in the ordinal scale with ascending hierarchy of CSPH risk: Level 1,<0.30 risk;Level 2,0.30-0.45 risk;Level 3, 0.45-0.60 risk;Level 4, 0.60-0.85 risk;and Level 5, >0.85 risk. Expected clinical events at 2 years of follow-up (PREDESCI study and others on natural history of liver cirrhosis) with added effect of decompensation, HCC and death:20% of clinical events at 2 years (16% decompensations,2% hepatocellular carcinomas and 2% deaths). | 24 months |
| Time-dependent composite clinical endpoint | Time to occurrence of the composite endpoint of only clinical events until study termination. | End of Follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate if the administration of zinc decreases the risk of having the first decompensation and what type. | Number of descompensations: First descompensation, hepatocellular carcinoma, liver related-death, liver transplantation. | 24 months |
| Evaluate if the administration of zinc decreases the risk of CSPH estimated by the ANTICIPATE model. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Joan Genescá, MD, PhD | Contact | 934 89 30 00 | joan.genesca@vallhebron.cat |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitari Vall d'Hebron | Recruiting | Barcelona | 08035 | Spain |
Not provided
| ID | Term |
|---|---|
| D006975 | Hypertension, Portal |
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
Not provided
Not provided
| ID | Term |
|---|---|
| C018802 | 6-acetylaminocaproic acid |
Not provided
Not provided
Not provided
| OTHER |
| Hospital Universitario Central de Asturias | OTHER |
| Complejo Hospitalario de Toledo | OTHER |
| Germans Trias i Pujol Hospital | OTHER |
| Hospital Universitario Marqués de Valdecilla | OTHER |
| Hospital Miguel Servet | OTHER |
| Parc Taulí Hospital Universitari | OTHER |
| Hospital de la Santa creu i Sant Pau - Barcelona | OTHER |
| Hospital Universitari de Bellvitge | OTHER |
| Hospital del Mar | OTHER |
| University Hospital of Girona Dr. Josep Trueta | NETWORK |
Phase III, randomized, double-blind clinical trial with two parallel groups, controlled with placebo. This is a low-level intervention clinical trial since the experimental drug is an authorized medication. This is a multicenter national study with fifteen Spanish centers recruiting patients
Not provided
Not provided
Not provided
|
|
Odds Ratio |
| 24 months |
| Evaluate if the administration of zinc reduces the risk of hepatocellular carcinoma. | Odds Ratio | 24 months |
| Evaluate if the administration of zinc reduces the risk of bacterial infections. | Odds Ratio | 24 months |
| Evaluate if the administration of zinc improves overall transplant-free survival and the risk of liver-related death. | Odds Ratio | 24 months |
| Evaluate if the administration of zinc improves liver function as measured by Child-Pugh and End-stage Liver Disease (MELD) score. | Child-Pugh: 5 (better outcome) to 15 (worse outcome). Child- Pugh has not an unabbreviated title. MELD: 6 (better outcome) to 40 (worse outcome) | 24 months |
| D009375 |
| Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |