Allopurinol to Prevent Cirrhosis Related Morbidities
Condition: Cirrhosis
MeSH terms: Liver Cirrhosis; Fibrosis
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): Placebo; Allopurinol 300 MG
Intervention type(s): Drug; Drug
Intervention description(s): not containing drugs; a competitive xanthine oxidase inhibitor, reduces oxidative stress and attenuates bacterial translocation
Intervention MeSH terms: Allopurinol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention