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

NCT05057572 | Completed

• 1 other identifier: ILBS-Cirrhosis-44
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Liver Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Complicated ascites (any of refractory ascites, SBP, AKI-HRS)

  1 year

Secondary Outcomes (28)

• Ascites resolution in both groups

  3 Months

• Ascites resolution in both groups

  6 Months

• Ascites resolution in both groups

  1 year

• Need and frequency of Large Volume Paracentesis

  1 year

• Incidence of PICD in 1 year

  1 year

Study Arms (2)

Carvedilol with Standard Medical Treatment

EXPERIMENTAL

Arm A will receive carvedilol plus standard medical therpy,Carvedilol: will be started with initial dose of 3.125 mg BD then After 3 days, increase the dose to 6.25 mg BD, Maximum dose would be 12.5 mg BD, the same shall be switch to Maximum tollrated dose if SBP \>90, HR \>55.

Drug: Carvedilol; Drug: Standard Medical Treatment

Standard Medical Treatment

ACTIVE COMPARATOR

\- Arm B will receive standard medical therapy.SMT (as described) that is Grade II ascites - Lasilactone (20/50) OD then Change after 1 week as per response, monitor diuretic intolerance.

Drug: Standard Medical Treatment

Interventions

Carvedilol DRUG

\- Arm A will receive carvedilol plus standard medical therpy,Carvedilol: will be started with initial dose of 3.125 mg BD then After 3 days, increase the dose to 6.25 mg BD, Maximum dose would be 12.5 mg BD, the same shall be switch to Maximum tollrated dose if SBP\>90, HR \>55.

Carvedilol with Standard Medical Treatment

Standard Medical Treatment DRUG

* Arm B will receive standard medical therapy.SMT (as described) that is Grade II ascites - Lasilactone (20/50) OD then Change after 1 week as per response, monitor diuretic intolerance. * Grade III ascites will undergo large volume paracentesis, lasilactone (20/50) OD Both groups will receive albumin as indicated (LT references as per protocol will be send for eligible patients)

Carvedilol with Standard Medical Treatment; Standard Medical Treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years
• Liver cirrhosis
• Grade II-III high SAAG ascites
• Small low risk or no esophageal varices
• CTP 7-12

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

Related Publications (1)

• Khajuria R, Jindal A, Sharma MK, Arora V, Vyas AK, Kumar G, Sarin SK. Efficacy and Safety of Carvedilol in Cirrhosis Patients With New-Onset Uncomplicated Ascites Without High-Risk Esophageal Varices (CARVE-AS Trial). Am J Gastroenterol. 2025 Jul 21. doi: 10.14309/ajg.0000000000003650. Online ahead of print.

  PMID: 40689908 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2021
• First Posted: September 27, 2021
• Study Start: October 1, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 20, 2025

Record last verified: 2025-03

Locations

IN (1)