Efficacy and Safety of Carvedilol in Cirrhosis Patients With Uncomplicated Ascites Without High Risk Esophageal Varices

• Status: Recruiting
• Trial end date: 2023-08-30
• Target enrollment: 0
• Participant gender: All

Summary

The cumulative risk of refractory ascites is in the order of 20% within five years of the development of ascites. An elevated sinusoidal pressure is essential for the development of ascites, as fluid accumulation does not develop at portal pressure gradient below 8 mm Hg, and rising corrected sinusoidal pressure correlates with decreased 24-hour urinary excretion of sodium.More recently, it has been hypothesised that bacterial translocation associated with portal hypertension in cirrhosis and related pathogen-associated, molecular pattern activated innate immune responses lead to systemic inflammation.This is associated with vasodilatation as well as release of proinflammatory cytokines, reactive oxygen and nitrogen species, contributing to organ dysfunction.This activates sympathetic nervous system stimulating reabsorption of sodium in proximal,distal tubules, loop of Henle and collecting duct as well as the renin-angiotensin-aldosterone system, leading to sodium absorption from distal tubule and collecting duct.[5]Renal sodium retention and eventual free water clearance due to non-osmoticrelease of arginine-vasopressin and its action on V2 receptor in the collectingduct underlie the fluid retention associated with oedema and ascites in cirrhosis.The lowering of portal pressure using non selective beta blocker has also been shown to reduce the development of ascites, refractory ascites and hepatorenal syndrome.Furthermore, the effect of non slective beta blocker on intestinal permeability, bacterial translocation and inflammatory response has been proposed to mitigate the risk of developing spontaneous bacterial peritonitis.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institute of Liver and Biliary Sciences, India
• Treatments: Carvedilol

Criteria

Inclusion Criteria:

• Age 18-65 years

• Liver cirrhosis

• Grade II-III high SAAG ascites

• Small low risk or no esophageal varices

• CTP 7-12

Exclusion Criteria:

• Age <18 years

• AKI at enrollement (Prior transient volume responsive AKI stage I included)

• Post renal or liver transplantation

• History of CAD, PVD, ventricular arrythmia, Bronchial asthma

• SBP at diagnosis

• Severe Hyponatremia (Na <125 MEq/L)

• Grade II/III/IV HE

• Advanced HCC (BCLC C,D), PVTT, Pregnancy or Lactating mother

• High risk varices (Large varices or small high risk varices)

• CTP >12

• ACLF

• Mixed / TB ascites

• Bilirubin >5 mg/dl

• Known CKD, obstructive uropathy

• Patient on MV, NIV, systemic sepsis and shock

• Lack of informed consent

• Prior intolerance or S/E to carvedilol or diuretics