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

Institute of Liver and Biliary Sciences, India

Status: Enrolling

Conditions: Liver Cirrhosis

Treatments: Drug: Carvedilol; Drug: Metformin

Study type: Interventional

Funder types: Other

Identifiers

NCT07108075

ILBS-ACLF-25

Details and patient eligibility

About

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.

Enrollment: 72 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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72 participants in 2 patient groups

Metformin and Carvedilol

Experimental group

Description:

Metformin (1000 mg) Carvedilol (12.5 mg)

Treatment:

Drug: Metformin

Drug: Carvedilol

Carvedilol

Active Comparator group

Description:

Carvedilol (12.5 mg)

Treatment:

Drug: Carvedilol