Zinc Supplementation to Improve Prognosis in Patients With Compensated Advanced Chronic Liver Disease: A Multicenter, Randomized, Double-blind, Placebo Controlled Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Time-dependent composite clinical endpoint
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Zinc Acexamate
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.
干预措施: Zinc Acexamate (Drug)
Placebo
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).
干预措施: Zinc Acexamate (Drug)
结局指标
主要结局
Time-dependent composite clinical endpoint
时间窗: End of Follow-up
Time to occurrence of the composite endpoint of only clinical events until study termination.
Values 1-6. Ordinal scale to assess efficacy of the intervention.
时间窗: 24 months
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).
次要结局
- Evaluate if the administration of zinc reduces the risk of hepatocellular carcinoma.(24 months)
- Evaluate if the administration of zinc improves liver function as measured by Child-Pugh and End-stage Liver Disease (MELD) score.(24 months)
- 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 improves overall transplant-free survival and the risk of liver-related death.(24 months)
- Evaluate if the administration of zinc reduces the risk of bacterial infections.(24 months)