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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin and Carvedilol | Experimental | Metformin (1000 mg) Carvedilol (12.5 mg) |
|
| Carvedilol | Active Comparator | Carvedilol (12.5 mg) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carvedilol | Drug | Carvedilol 12. 5mg |
| |
| Measure | Description | Time Frame |
|---|---|---|
| HVPG response (decrease by ≥ 20 % from baseline or < 12 mmHg). | 2 hours |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
- Consecutive patients of cirrhosis with variceal bleed.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Dr Garvit Mundra, MD | Contact | 01146300000 | garvitmundra@gmail.com | |
| Dr Chitranshu Vashishtha, DM | Contact | 01146300000 | chitranshuv@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Liver & Biliary Sciences (ILBS) | Recruiting | New Delhi | National Capital Territory of Delhi | 110070 | India |
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| ID | Term |
|---|---|
| D008103 | Liver Cirrhosis |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D000077261 | Carvedilol |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| Metformin |
| Drug |
Metformin 1000 mg |
|
| 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 |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D020005 |
| Propanols |
| D000588 | Amines |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |