Allopurinol to Prevent Cirrhosis Related Morbidities

NCT ID: NCT05545670

Last Updated: 2023-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-15
• Study Completion Date: 2023-03-01

Brief Summary

The study aims to compare the potential benefit of allopurinol 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 rate.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).

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

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 cirrhosis.

Intestinal permeability plays a role in the development of bacterial translocation and may be involved in the development of complications of cirrhosis. 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 cytokines.

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 oxidase.

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 scavenger.

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.

Conditions

Cirrhosis

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

Interventions

Placebo

not containing drugs

Intervention Type: DRUG

Allopurinol 300 MG

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ge 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

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Faculty of Pharmacy

Tanta, , Egypt

Countries

Egypt

References

Glal KAM, El-Haggar SM, Abdel-Salam SM, Mostafa TM. Allopurinol Prevents Cirrhosis-Related Complications: A Quadruple Blind Placebo-Controlled Trial. Am J Med. 2024 Jan;137(1):55-64. doi: 10.1016/j.amjmed.2023.09.016. Epub 2023 Oct 12.

Reference Type: DERIVED

PMID: 37832758 (View on PubMed)

Other Identifiers

allopurinol in cirrhosis

Identifier Type: -

Identifier Source: org_study_id