Clinical trial NCT06434753: Zinc Supplementation to Improve Prognosis in Patients With Compensated Advanced Chronic Liver Disease.
Official title: Zinc Supplementation to Improve Prognosis in Patients With Compensated Advanced Chronic Liver Disease: A Multicenter, Randomized, Double-blind, Placebo Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Advanced Chronic Liver Disease
Portal Hypertension
Hepatocellular Carcinoma
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
Collaborators: name: Hospital General Universitario Gregorio Marañon
name: Hospital Vall d'Hebron
name: Hospital Universitario Puerta del Hierro
name: Hospital Clinic of Barcelona
name: Hospital Universitario Central de Asturias
name: Complejo Hospitalario de Toledo
name: Germans Trias i Pujol Hospital
name: Hospital Universitario Marqués de Valdecilla
name: Hospital Miguel Servet
name: Parc Taulí Hospital Universitari
name: Hospital de la Santa creu i Sant Pau - Barcelona
name: Hospital Universitari de Bellvitge
name: Hospital del Mar
name: University Hospital of Girona Dr.Josep Trueta
First posted: 2024-05-30
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Values 1-6. Ordinal scale to assess efficacy of the intervention.
timeFrame: 24 months
measure: Time-dependent composite clinical endpoint
timeFrame: End of Follow-up
Secondary outcomes:
measure: Evaluate if the administration of zinc decreases the risk of having the first decompensation and what type.
timeFrame: 24 months
measure: Evaluate if the administration of zinc decreases the risk of CSPH estimated by the ANTICIPATE model.
timeFrame: 24 months
measure: Evaluate if the administration of zinc reduces the risk of hepatocellular carcinoma.
timeFrame: 24 months
measure: Evaluate if the administration of zinc reduces the risk of bacterial infections.
timeFrame: 24 months
measure: Evaluate if the administration of zinc improves overall transplant-free survival and the risk of liver-related death.
timeFrame: 24 months
measure: Evaluate if the administration of zinc improves liver function as measured by Child-Pugh and End-stage Liver Disease (MELD) score.
timeFrame: 24 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
References: