Zinc Supplementation to Improve Prognosis in Patients With Compensated Advanced Chronic Liver Disease.

NCT06434753 | Recruiting Phase 3

• 1 other identifier: IC/LV/ACZ/PCHC
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Advanced Chronic Liver Disease; Portal Hypertension; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (6)

• Evaluate if the administration of zinc decreases the risk of having the first decompensation and what type.

  24 months

• Evaluate if the administration of zinc decreases the risk of CSPH estimated by the ANTICIPATE model.

  24 months

• Evaluate if the administration of zinc reduces the risk of hepatocellular carcinoma.

  24 months

• Evaluate if the administration of zinc reduces the risk of bacterial infections.

  24 months

• Evaluate if the administration of zinc improves overall transplant-free survival and the risk of liver-related death.

  24 months

Study Arms (2)

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.

Drug: Zinc Acexamate

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).

Drug: Zinc Acexamate

Interventions

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).

Also known as: Placebo

Placebo; Zinc Acexamate

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of both sexes with diagnosed compensated advanced chronic liver disease (cACLD) determined by hepatic stiffness on transient elastography \>15 kPa.
• Age between 18 and 80 years, inclusive.
• Absence of prior or current decompensation.
• For women of childbearing age, a possible pregnancy will be ruled out by a pregnancy test prior to the start of the study. Following the test, the woman must use an effective contraceptive method during sexual intercourse (see Appendix I) in the days leading up to the start of treatment, and continue to use it throughout the treatment period, as well as for several days after its completion.
• Signing of informed consent.

You may not qualify if:

• History or current presence of hepatocellular carcinoma.
• Concomitant systemic disease with a short-term poor prognosis.
• Pregnancy, breastfeeding, or refusal to use contraceptive measures during participation in the study.
• Patients with compensated advanced chronic liver disease (cACLD) due to hepatitis B virus (HBV) under antiviral treatment, and those with cACLD due to hepatitis C virus (HCV) cured with antiviral treatment.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead
• Hospital General Universitario Gregorio Marañon: collaborator
• Hospital Vall d'Hebron: collaborator
• Hospital Universitario Puerta del Hierro: collaborator
• Hospital Clinic of Barcelona: collaborator
• Hospital Universitario Central de Asturias: collaborator
• Complejo Hospitalario de Toledo: collaborator
• Germans Trias i Pujol Hospital: collaborator
• Hospital Universitario Marqués de Valdecilla: collaborator
• Hospital Miguel Servet: collaborator
• Parc Taulí Hospital Universitari: collaborator
• Hospital de la Santa creu i Sant Pau - Barcelona: collaborator
• Hospital Universitari de Bellvitge: collaborator
• Hospital del Mar: collaborator
• University Hospital of Girona Dr. Josep Trueta: collaborator

Study Sites (1)

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

MeSH Terms

Conditions

Hypertension, Portal; Carcinoma, Hepatocellular

Interventions

6-acetylaminocaproic acid

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Central Study Contacts

Joan Genescá, MD, PhD

CONTACT

934 89 30 00; joan.genesca@vallhebron.cat

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: April 30, 2024
• First Posted: May 30, 2024
• Study Start: October 2, 2022
• Primary Completion: March 2, 2026
• Study Completion: March 2, 2026
• Last Updated: June 4, 2024

Record last verified: 2024-06

Locations

ES (1)