To Study the Effect of Nonselective Beta Blockers in Advanced Stage Liver Disease With Ascites
Condition: Ascites
MeSH terms: Liver Diseases; Ascites
Study type: Interventional
Phase: Phase 3

Summary: 
      Cirrhosis is the leading cause of death in India and worldwide and leading causes in
      developed world include alcoholic liver disease, hepatitis C, and more recently,
      non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH). As cirrhosis
      advances, portal hypertension develops, resulting in complications such as ascites, hepatic
      encephalopathy, and variceal hemorrhage.

      Ascites is the most common major complication of cirrhosis, occurring in 50-60% of patients
      within ten years of diagnosis . Development of ascites is an ominous landmark in disease
      progression as 15% of patients with ascites will die within 1 year, and 44% within 5 years.
      Less than 10% patients develop refractory ascites and is associated with a poor prognosis
      with a high mortality, approximately 50% within 6 months and 75% at 1 year with the median
      survival approximately 6 months . Refractory ascites occurs as a result of splanchnic
      vasodilatation and maximal activation of the sympathetic nervous system (SNS) and the renin -
      aldosterone system (RAAS) . The therapeutic options available for these patients are serial
      therapeutic paracentesis, liver transplantation and trans jugular intrahepatic portosystemic
      shunts .The model for end stage liver disease( MELD) score predicts survival in patients with
      cirrhosis . However, other factors in patients with cirrhosis and ascites are also associated
      with poor prognosis, including low mean arterial pressure; low serum sodium, low urine
      sodium, and high Child-Pugh score .

      Variceal bleed is the most dreaded complication of cirrhosis and screening endoscopic is
      recommend in these patients. About 60% of patients with decompensated cirrhosis have varices
      at the time of diagnosis. Majority of these patients will require non selective beta blockers
      (NSBB) as standard of care as primary or secondary prophylaxis in prevention of variceal
      hemorrhage. NSBB reduce portal pressure by decreasing cardiac output and by producing
      splanchnic vasoconstriction.. Endoscopic variceal band ligation (EVL) is another modality of
      treatment of esophageal varices and meta-analysis showed EVL to be associated with
      significantly lower incidence of first variceal hemorrhage without differences in mortality
      compared to NSBB. NSBB also has shown to improve survival in these patients with
      nonhemodynamic effects. Some of the patients may progress to end stage liver disease
      characterized by the development of refractory ascites and other complications.

      Most of the studies of NSBB comparing to EVL for primary/secondary prevention of variceal
      hemorrhage included patients of predominantly child A/B cirrhosis with variable number with
      ascites without any mention of ascites grading and some of trials excluded patient's with
      refractory ascites. These patients with ascites received diuretics and salt restricted diet
      as standard of care. However none of these studies mentioned about control of ascites and
      survival benefit in patients with advanced stage (child B and C) cirrhosis with ascites .In
      recent years the role of NSBB for prevention of variceal hemorrhage in refractory ascites
      patients has been questioned because of the deleterious effect on survival.However the use of
      NSBB in end stage liver disease has shown mixed results and controversial.

      Therefore this study is being planned to know the effects of NSBB in advanced stage liver
      disease patients with ascites and varices in preventing variceal hemorrhage ,effect on
      ascites and survival.
    


Intervention name(s): Propranolol; Endoscopic variceal ligation (EVL)
Intervention type(s): Drug; Procedure
Intervention description(s): Propranolol will be started at a dose of 40 mg and will be titrated based on pulse rate with target of 55-60 beats per minute or 20-25% reduction in heart rate and maximum tolerated dose.If any patients develop intolerable side effects, they will be withdrawn from the study; Patients in EVL group will undergo regular sessions of UGIE with EVL till variceal eradication every 2- 4 weekly followed by 3 monthly for initial 6 months and 6 monthly in rest of the study period. If any patient develop acute variceal hemorrhage on follow up , will be treated inpatient with standard medical therapy(SMT) .
Intervention MeSH terms: Propranolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Non selective beta blockers; Ascites