Clinical Trial: To Study the Effect of Nonselective Beta Blockers in Advanced Stage Liver Disease With Ascites

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: To Study the Effect of Nonselective Beta Blockers in Advanced Stage Liver Disease With Ascites

Brief 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 prop

Detailed Summary:
Sponsor: Postgraduate Institute of Medical Education and Research

Current Primary Outcome: Survival [ Time Frame: Upto 48 weeks ]

It is a categorical variable-patient dead/alive


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Acute kidney injury (AKI) [ Time Frame: Upto 48 weeks ]
    Occurence of AKI will be noted in each group during 48 weeks follow up. The event, AKI is defined as Increase in sCr ≥0.3 mg/dl (≥26.5 μmol/L) within 48 hours; or,A percentage increase sCr ≥50% from baseline which is known, or presumed, to have occurred within the prior 7 days during study period. AKI will be treated accordingly.
  • Spontaneous bacterial peritonitis [ Time Frame: 1 year ]
    The diagnosis is based on neutrophil count in ascitic fluid of >250/mm3 as determined by microscopy. Incidence will be noted at each follow up
  • Hepatorenal syndrome( HRS) [ Time Frame: 1 year ]

    HRS is defined as the occurrence of renal failure in a patient with advanced liver disease in the absence of an identifiable cause of renal failure. Criteria for the diagnosis include-

    • Cirrhosis with ascites
    • Serum creatinine >1.5 mg/dl (133 lmol/L)
    • Absence of shock

    • Absence of hypovolemia as defined by no sustained improvement of renal function (creatinine decreasing to <133 lmol/L) following at least 2 days of diuretic withdrawal (if on diuretics), and volume expansion with albumin at

      1 g/kg/day up to a maximum of 100 g/day

    • No current or recent treatment with nephrotoxic drugs
    • Absence of parenchymal renal disease as defined by proteinuria <0.5 g/day, no microhaematuria (<50 red cells/high powered field), and normal renal ultrasonography.

    Incidence of HRS will be noted at each follow up.

  • Control of ascites [ Time Frame: Upto 48 weeks ]

    Control of ascites will be assesed by clinical examination in each follow up and response to therapy will be defined as follows:

    1. Complete Response - Elimination of ascites
    2. Partial Response- Presence of ascites not requiring paracentesis.
    3. Absence of response - Persistence of ascites requiring paracentesis

    This parameter will be noted during follow up.

  • Incidence of variceal hemorrhage in each group [ Time Frame: 1 year ]
    Occurence of variceal hemorrhage during follow up period will be noted
  • Incidence of Paracentesis induced circulatory dysfunction (PICD) in different groups during LVP [ Time Frame: Upto 48 weeks ]
    PICD is defined as Increase in plasma renin activity of >50% of the pretreatment value on day 7 after each large volume paracentesis.


Original Secondary Outcome: Same as current

Information By: Postgraduate Institute of Medical Education and Research

Dates:
Date Received: December 5, 2015
Date Started: July 2015
Date Completion: December 2016
Last Updated: January 5, 2016
Last Verified: January 2016