To Study the Effect of Nonselective Beta Blockers in Advanced Stage Liver Disease With Ascites
Status:
Unknown status
Trial end date:
2016-12-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 3
Details
Lead Sponsor:
Postgraduate Institute of Medical Education and Research