Acute Hemodynamic Response to Carvedilol in Children With Clinically Significant Portal Hypertension.

NCT05767229 | Completed

• 1 other identifier: ILBS-Cirrhosis-56
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Clinically significant portal hypertension (CSPH) is defined as Hepatic Venous Pressure gradient (HVPG) \>10 mmHg. Patients with CSPH are at risk of developing esophageal varices and clinical decompensation (variceal bleeding, ascites, jaundice, encephalopathy), which mark the transition from compensated stage to a stage of the disease (decompensated) associated with higher mortality. HVPG is calculated by subtracting the free hepatic venous pressure (FHVP), a measure of systemic pressure, from the wedged hepatic venous pressure (WHVP), a measure of hepatic sinusoidal pressure. HVPG is surrogate marker in many clinical applications such as gold standard test to evaluate presence and severity of portal hypertension (PHT) diagnosis, risk stratification, monitoring of the patients on beta blockers. Non-selective beta-blockers like propranolol and carvedilol are indicated in adults for primary and secondary prophylaxis of variceal hemorrhage. Acute hemodynamic response to intravenous propranolol with HVPG values coming down to \< 12 mm Hg or reduction to \>20% from baseline have been shown to be associated with reduced long-term risk of variceal bleed. Portal Hypertension in biliary atresia (BA) occurs early and is due to recurrent cholangitis and portal sclerosis. HVPG in children is feasible and safe in children according to previous studies, however, there are no recommendations to suggest beta-blockers based on HVPG reduction in children. Hence, we are planning the current work to study the acute hemodynamic response to carvedilol in children with CSPH, and to compare the HVPG values in children with chronic liver disease.

Conditions

Portal Hypertension

Outcome Measures

Primary Outcomes (1)

• Proportion of children with acute hemodynamic response 90 mins after carvedilol given through nasogastric route) in those with clinically significant portal hypertension.

  Acute hemodynamic response (HVPG reduction to less than 12 mm Hg or by more than equals to 20% from initial value

  90 minutes

Secondary Outcomes (7)

• HVPG values in children (2-18 years age) with different etiologies of chronic liver disease.

  Day 0

• Proportion of children with presence of varices and clinically significant varices in children with HVPG more than equal to 10 in different etiologies of liver disease..

  Day 0

• Proportion of children with presence of varices and clinically significant varices in children with HVPG less than 10 mm Hg in different etiologies of liver disease.

  Day 0

• Splenic Z-scores, Liver and splenic stiffness in children with HVPG more than equal to 10 or less than 10 mm Hg in different etiologies of liver disease.

  Day 0

• Bile acid levels in children with HVPG more than equal to 10 or less than 10 mm Hg in different etiologies of liver disease.

  Day 0

Study Arms (1)

Carvedilol for 1.5 hrs

EXPERIMENTAL

Carvedilol 0.2 mg/kg for 1.52 hrs

Drug: Carvedilol

Interventions

Carvedilol DRUG

Carvedilol 0.2 mg/kg for 1.5 hrs

Carvedilol for 1.5 hrs

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• All children 2-18 years of age with CLD defined as presence of either of the following histological evidence of advanced fibrosis more than F2 on METAVIR staging or radiological imaging suggestive (heterogeneous hepatic echotexture, irregular nodular liver and/or caudate hypertrophy). .
• Splenomegaly and/or platelets \</= 100 (X10\^3/mm3)
• Coming for upper gastrointestinal endoscopy for variceal screening
• Informed consent for HVPG and UGIE

You may not qualify if:

• Uncorrected heart defects (except small ASD)
• Cardiac conduction defects - arrythmias or heart block
• Interrupted inferior vena cava
• Situs inversus
• Patients who received beta-blockers in last 7 days
• Patients who received Octreotide infusion or bolus in last 7 days
• Variceal bleed in last 48 hours
• Shock or active sepsis
• Grade 2 /grade 3 ascites
• Severe hepatic impairment with MELD or PELD score \>14
• Acute kidney injury (any grade)
• Hepatic encephalopathy (any grade)
• Known contraindications to propranolol in children:
• Hyper-reactive airway disease
• Hypertrophic cardiomyopathy

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

MeSH Terms

Conditions

Hypertension, Portal

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: March 14, 2023
• Study Start: March 13, 2023
• Primary Completion: November 2, 2024
• Study Completion: November 2, 2024
• Last Updated: January 8, 2025

Record last verified: 2025-01

Locations

IN (1)