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

Not Applicable

Recruiting

• Conditions: Liver Cirrhosis
• Interventions: Drug: Carvedilol; Drug: Metformin

• Registration Number: NCT07108075
• Lead Sponsor: Institute of Liver and Biliary Sciences, India

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-06-14
• Status Verified: 2025-07
• Study First Submitted: 2025-07-15
• Study First Submitted QC: 2025-07-30
• Last Update Submitted: 2025-07-30
• Study First Posted: 2025-08-06
• Last Update Posted: 2025-08-06
• Primary Completion: 2025-10-30
• Study Completion: 2025-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

• Consecutive patients of cirrhosis with variceal bleed.

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin and Carvedilol	Carvedilol	Metformin (1000 mg) Carvedilol (12.5 mg)
Metformin and Carvedilol	Metformin	Metformin (1000 mg) Carvedilol (12.5 mg)
Carvedilol	Carvedilol	Carvedilol (12.5 mg)

Primary Outcome Measures

Name	Time	Method
HVPG response (decrease by ≥ 20 % from baseline or < 12 mmHg).	2 hours

Secondary Outcome Measures

Name	Time	Method
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
Change in cardiac output in both groups.	2 hours

Trial Locations

Locations (1)

Institute of Liver & Biliary Sciences (ILBS); 🇮🇳 New Delhi, Delhi, India