## Protocol Section
### Identification Module
**NCT ID:** NCT06434753

**Brief Title:** 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

#### Organization Study ID Info
**ID:** IC/LV/ACZ/PCHC
#### Organization
**Class:** OTHER
**Full Name:** Hospital Universitari Vall d'Hebron Research Institute
### Status Module
#### Completion Date
**Date:** 2026-03-02

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2026-03-02

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-10-02

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-30
**Study First Submit QC Date:** 2024-05-23
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Hospital General Universitario Gregorio Marañon

**Class:** OTHER

**Name:** Hospital Vall d'Hebron

**Class:** UNKNOWN

**Name:** Hospital Universitario Puerta del Hierro

**Class:** OTHER

**Name:** Hospital Clinic of Barcelona

**Class:** OTHER

**Name:** Hospital Universitario Central de Asturias

**Class:** OTHER

**Name:** Complejo Hospitalario de Toledo

**Class:** OTHER

**Name:** Germans Trias i Pujol Hospital

**Class:** OTHER

**Name:** Hospital Universitario Marqués de Valdecilla

**Class:** OTHER

**Name:** Hospital Miguel Servet

**Class:** OTHER

**Name:** Parc Taulí Hospital Universitari

**Class:** OTHER

**Name:** Hospital de la Santa creu i Sant Pau - Barcelona

**Class:** OTHER

**Name:** Hospital Universitari de Bellvitge

**Class:** OTHER

**Name:** Hospital del Mar

**Class:** NETWORK

**Name:** University Hospital of Girona Dr.Josep Trueta

#### Lead Sponsor

**Class:** OTHER

**Name:** Hospital Universitari Vall d'Hebron Research Institute

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**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 Module

**Conditions:**

- Advanced Chronic Liver Disease

- Portal Hypertension

- Hepatocellular Carcinoma

### Design Module

#### Design Info

**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

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 300

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Drug: Zinc Acexamate

**Label:** Zinc Acexamate

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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).

**Intervention Names:**

- Drug: Zinc Acexamate

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Placebo

- Zinc Acexamate

**Description:** 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).

**Name:** Zinc Acexamate

**Other Names:**

- Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Ordinal scale to assess efficacy of the intervention, with the 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 primary endpoint will be assessed at the two-year mark as the distribution of patients in a 6-value ordinal scale. The most severe category (Value 6) will be the development of clinical events: First descompensation, hepatocellular carcinoma, liver related-death, liver transplantation.

This ordinal scale captures both the development of clinical events (level 6), and the risk of presenting them, based on the ANTICIPATE model. Considering the sum of expected clinical events at 24 months of follow-up according to the PREDESCI study and other studies on the natural history of liver cirrhosis with the added effect of decompensation, HCC and death, a total of 20% of clinical events are expected at two years of follow-up (16% decompensations, 2% hepatocellular carcinomas and 2% deaths).

**Measure:** Values 1-6. Ordinal scale to assess efficacy of the intervention.

**Time Frame:** 24 months

#### Secondary Outcomes

**Description:** Number of descompensations: First descompensation, hepatocellular carcinoma, liver related-death, liver transplantation.

**Measure:** Evaluate if the administration of zinc decreases the risk of having the first decompensation and what type.

**Time Frame:** 24 months

**Description:** Odds Ratio

**Measure:** Evaluate if the administration of zinc decreases the risk of CSPH estimated by the ANTICIPATE model.

**Time Frame:** 24 months

**Description:** Odds Ratio

**Measure:** Evaluate if the administration of zinc reduces the risk of hepatocellular carcinoma.

**Time Frame:** 24 months

**Description:** Odds Ratio

**Measure:** Evaluate if the administration of zinc reduces the risk of bacterial infections.

**Time Frame:** 24 months

**Description:** Odds Ratio

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

**Time Frame:** 24 months

**Description:** Score (Child-Pugh and MELD)

**Measure:** Evaluate if the administration of zinc improves liver function as measured by Child-Pugh and MELD score.

**Time Frame:** 24 months

### Eligibility Module

**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.

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** joan.genesca@vallhebron.cat

**Name:** Joan Genescá, MD, PhD

**Phone:** 934 89 30 00

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Barcelona

**Contacts:**

***Contact 1:***

- **Name:** Joan Genescá, MD, PhD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitari Vall d'Hebron

**Status:** RECRUITING

**Zip:** 08035

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004066

- Term: Digestive System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10024

- Name: Hypertension

- Relevance: LOW

- As Found: Unknown

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M9613

- Name: Carcinoma, Hepatocellular

- Relevance: LOW

- As Found: Unknown

- ID: M11107

- Name: Liver Diseases

- Relevance: HIGH

- As Found: Liver Disease

- ID: M10026

- Name: Hypertension, Portal

- Relevance: HIGH

- As Found: Portal Hypertension

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008107

- Term: Liver Diseases

- ID: D000006975

- Term: Hypertension, Portal

### Intervention Browse Module - Ancestors

- ID: D000000894

- Term: Anti-Inflammatory Agents, Non-Steroidal

- ID: D000018712

- Term: Analgesics, Non-Narcotic

- ID: D000000700

- Term: Analgesics

- ID: D000018689

- Term: Sensory System Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000893

- Term: Anti-Inflammatory Agents

- ID: D000018501

- Term: Antirheumatic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Analg

- Name: Analgesics

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: Micro

- Name: Micronutrients

### Intervention Browse Module - Browse Leaves

- ID: M164210

- Name: 6-acetylaminocaproic acid

- Relevance: HIGH

- As Found: Fagerström Test for Nicotine Dependence

- ID: M11110

- Name: Liver Extracts

- Relevance: LOW

- As Found: Unknown

- ID: M17768

- Name: Zinc

- Relevance: LOW

- As Found: Unknown

- ID: M4217

- Name: Anti-Inflammatory Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4218

- Name: Anti-Inflammatory Agents, Non-Steroidal

- Relevance: LOW

- As Found: Unknown

- ID: M4032

- Name: Analgesics

- Relevance: LOW

- As Found: Unknown

- ID: M20786

- Name: Analgesics, Non-Narcotic

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000018802

- Term: 6-acetylaminocaproic acid

### Misc Info Module

- Version Holder: 2024-05-31
