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

Official title

Acute Portal Pressure Reduction by Metformin and Carvedilol Compared to Carvedilol Alone in Cirrhosis - a Randomised, Double Blind Study.

Overview

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.

Interventions

• Drug Carvedilol
  Carvedilol 12. 5mg
• Drug Metformin
  Metformin 1000 mg

Primary outcome measures

• HVPG response (decrease by ≥ 20 % from baseline or < 12 mmHg). [Time frame: 2 hours]

Secondary outcome measures (6)

• HVPG decrease by ≥ 10% in both groups. [Time frame: 2 hours]
• Reduction in HVPG in both groups. [Time frame: 2 hours]
• Change in blood sugar level after 2 hours of the drug in both groups. [Time frame: 2 hours]
• Change in inflammatory markers (IL-10, TNF α, i-NOS, e-NOS) in both groups. [Time frame: 2 hours]
• Change in liver and spleen stiffness. [Time frame: 2 hours]
• Change in cardiac output in both groups. [Time frame: 2 hours]

Eligibility criteria

Inclusion criteria

\- Consecutive patients of cirrhosis with variceal bleed.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

India · 1 center

• Institute of Liver & Biliary Sciences (ILBS) — New Delhi

Identifiers

NCT: NCT07108075 · ILBS-ACLF-25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗