Allopurinol Versus Atorvastatin to Prevent Complications of Liver Cirrhosis

NCT ID: NCT05511766

Last Updated: 2023-04-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-15
• Study Completion Date: 2025-01-30

Brief Summary

The study aims to compare the potential benefit of allopurinol versus atorvastatin in reducing the risk of developing cirrhosis-related complications, delaying the onset of hepatocellular carcinoma, and improving survival. Furthermore, the study aims to evaluate their impact on parents' related quality of life.

Detailed Description

Cirrhosis is the late stage of liver damage and possess two phases: a compensated phase with favorable prognosis and a decompensated phase with high mortality rate1.The shift from compensated to decompensated cirrhosis is characterized by the onset of complications, including ascites, hepatic encephalopathy (HE), variceal bleeding, and spontaneous bacterial peritonitis (SBP) which are associated with substantial morbidity and negative Impact on quality of life (QOL)2.

The gut microbiota plays an important role in cirrhosis and development of cirrhosis-related complications3.

Indeed, translocation of endotoxins is increased in patients with cirrhosis and patients with more severe cirrhosis (i.e. Patients with decompensated cirrhosis, hospitalized patients) had significantly greater serum endotoxin concentrations that mediate complications of cirrhosis4.

Intestinal permeability plays a role in the development of bacterial translocation and may be involved in the development of complications of cirrhosis5. This 'leaky gut' phenomenon increases with the degree of liver failure and is particularly prominent in patients with cirrhosis who have experienced severe septic complications and has been implicated in the hepatic production of endotoxin-associated proinflammatory cytokines6.

Intestinal mucosa alterations at the subcellular level have been reported in experimental cirrhosis, in relation to an increased oxidative stress due to overactivity in the enzyme xanthine oxidase7.

Allopurinol, a competitive xanthine oxidase inhibitor, reduces oxidative stress and attenuates bacterial translocation in portal hypertensive animals, suggesting that the damaging effects of oxygen-derived free radicals and peroxidation on mucosal cells may be counteracted by a free radical scavenger8.

In 2007, a pilot study demonstrated that allopurinol in patients with cirrhosis is associated with a significant reduction in oxidative stress but no effect on intestinal permeability and inflammatory markers. The study duration was only 10 days and therefore another study with a long period of time is essential 9.

Statins are one class of medications being studied to determine their effect on progression and decompensation of CLDs. Besides their lipid-lowering effects, statins also decrease oxidative stress and inflammation by decreasing activation of inflammatory cells, and improve endothelial function by increasing synthesis of nitric oxide, restoring the function of endothelial cells, and increasing the number of endothelial progenitors cells10. Recent studies have suggested an association between statin use and hepatic decompensation in patients with CLDs11.

Cirrhosis and its complications have a substantial economic, social, and personal impact on affected patients, as well as their families and caregivers12. Given that the number of primary prophylaxis treatments that prevent complications of cirrhosis is limited. Therefore, it is important to examine whether allopurinol and statins have the potential to reduce the risk of developing several complications of cirrhosis, including HE, SBP, variceal bleeding, hepatocellular carcinoma (HCC) and hepatorenal syndrome.

Conditions

Cirrhosis; Hepatic Encephalopathy; Ascites; Varices; SBP - Spontaneous Bacterial Peritonitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

PLACEBO

Group1: (Placebo, n=50) who will receive oral placebo tablet once daily FOR 6 MONTHS

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

not containing drugs

Allopurinol

Group 2:(Allopurinol n=50) who will receive oral allopurinol 300 mg daily for 6 months

Group Type: ACTIVE_COMPARATOR

Allopurinol 300 MG

Intervention Type: DRUG

a competitive xanthine oxidase inhibitor, reduces oxidative stress and attenuates bacterial translocation

Simvastatin

Group 3: (atorvastatin n=50) who will receive oral atorvastatin 20 mg daily for 6 months

Group Type: ACTIVE_COMPARATOR

Atorvastatin 20mg

Intervention Type: DRUG

is lipid-lowering agent with anti-oxidative stress and anti-inflammation properties

Interventions

Allopurinol 300 MG

a competitive xanthine oxidase inhibitor, reduces oxidative stress and attenuates bacterial translocation

Intervention Type: DRUG

Atorvastatin 20mg

is lipid-lowering agent with anti-oxidative stress and anti-inflammation properties

Intervention Type: DRUG

Placebo

not containing drugs

Intervention Type: DRUG

Other Intervention Names

zyloric

Eligibility Criteria

Inclusion Criteria

• Age 18 to 75 years old
• Both sex
• Adults with cirrhosis in a stable conditions

Exclusion Criteria

• Active SBP
• Renal insufficiency (serum creatinine > 2.0 mg/dl)
• Active GIT hemorrhage

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tanta University

OTHER

Sponsor Role: lead

Responsible Party

Khadija Ahmed Mhrose Glal

Assistant lecturer of clinical pharmacy- Clinical pharmacy department- Faculty of pharmacy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

khadija glal

Role: PRINCIPAL_INVESTIGATOR

assistant lecturer

Locations

Tanta University

Tanta, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

khadija glal

Role: CONTACT

khadija.ahmed@pharm.tanta.edu.eg

01118969649

Facility Contacts

khadija

Role: primary

Other Identifiers

allopurinol v atorvastatin

Identifier Type: -

Identifier Source: org_study_id