Acute Portal Pressure Reduction by Metformin and Carvedilol Compared to Carvedilol Alone in Cirrhosis.

NCT07108075 | Recruiting

• 1 other identifier: ILBS-ACLF-25
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Clinically significant portal hypertension (CSPH) is defined as 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 (1). 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 (2). 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. Metformin has also recently showed to reduce portal pressure in a randomised control study. The mechanism of action of metformin is different from beta blockers (by increasing nitric oxide by upregulating iNOS and eNOS). Hence we are planning the current work to evaluate Acute portal pressure reduction by Metformin and Carvedilol compared to Carvedilol alone in cirrhosis - a randomised, double blind study.

Conditions

Liver Cirrhosis

Outcome Measures

Primary Outcomes (1)

• HVPG response (decrease by ≥ 20 % from baseline or < 12 mmHg).

  2 hours

Secondary Outcomes (6)

• HVPG decrease by ≥ 10% in both groups.

  2 hours

• Reduction in HVPG in both groups.

  2 hours

• Change in blood sugar level after 2 hours of the drug in both groups.

  2 hours

• Change in inflammatory markers (IL-10, TNF α, i-NOS, e-NOS) in both groups.

  2 hours

• Change in liver and spleen stiffness.

  2 hours

Study Arms (2)

Metformin and Carvedilol

EXPERIMENTAL

Metformin (1000 mg) Carvedilol (12.5 mg)

Drug: Carvedilol; Drug: Metformin

Carvedilol

ACTIVE COMPARATOR

Carvedilol (12.5 mg)

Drug: Carvedilol

Interventions

Carvedilol DRUG

Carvedilol 12. 5mg

Carvedilol; Metformin and Carvedilol

Metformin DRUG

Metformin 1000 mg

Metformin and Carvedilol

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Consecutive patients of cirrhosis with variceal bleed.

You may not qualify if:

• Age \< 18 and \> 75yr,
• CTP Score ≥12,
• Patients of cirrhosis without variceal bleed,
• Patients on metformin, nonselective β-blockers or carvedilol treatment within last 5 days,
• S.Bilirubin \> 3 mg/dl,
• S.creatinine 1.5 mg/dl,
• Contraindications to NSBB (heart rate \< 60 /min, BP \< 110/60 mm Hg,
• Asthma, heart failure),
• PVT,
• HCC
• HE grades 2-4

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences (ILBS)

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

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Carvedilol; Metformin

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; Biguanides; Guanidines; Amidines

Central Study Contacts

Dr Garvit Mundra, MD

CONTACT

01146300000; garvitmundra@gmail.com

Dr Chitranshu Vashishtha, DM

CONTACT

01146300000; chitranshuv@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2025
• First Posted: August 6, 2025
• Study Start: June 14, 2025
• Primary Completion: October 30, 2025
• Study Completion: October 30, 2025
• Last Updated: August 6, 2025

Record last verified: 2025-07

Locations

IN (1)