Efficacy of Nonselective Beta Blocker vs Placebo in Patients With Acute-on-chronic Liver Failure With Small/ no Esophageal Varices

Study Overview
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Brief Summary
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Acute on chronic liver failure patients with HVPG (Hepatic Venous Pressure Gradient) ≥ 12 mmHg + No/small esophageal varices who present to the Department of Hepatology at Institute of Liver and Billiary Sciences, who meet the inclusion criteria and who provide informed consent.

Official Title
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Efficacy of Nonselective Beta Blockers vs Placebo in Patients With Acute-on-chronic Liver Failure With Small/ no Esophageal Varices

Conditions
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Acute on Chronic Liver Failure

Intervention / Treatment
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* Drug: Carvedilol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute on Chronic Liver Failure as per APASL (Asian Pacific Association of Study of Liver Disease) criteria. 18-75 years HVPG ≥ 12 + No/Small Esophageal varices Exclusion Criteria: Bradycardia (HR < 60/ min) Hypotension Asthma LVF AKI (Acute Kidney Injury), (S.creat >1.5) Refractory ascites SBP (Spontaneous Bacterial Peritonitis) Pregnancy or Lactation Past history of EVL or EST Significant cardio - pulmonary co-morbidity PVT Presence of grades 3-4 hepatic encephalopathy (HE) Patients going for liver transplant in next 12 weeks No consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol<br>Tab Carvedilol 3.125 mg twice daily followed by 6.25 mg BD and finally 12.5 mg BD if SBP > 90 mmHg and HR >55/min | Drug: Carvedilol<br> <br> |
| Placebo Comparator: placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality in both groups |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with development or progression of esophageal varices in both groups. |  | 3 Months | 
| Number of patients with reduction in hepatic venous pressure gradient (HVPG) in both groups. |  | 3 Months | 
| Number of patients with regression in esophageal varices in both groups. |  | 3 Months | 
| Number of patients with improvement in Liver severity scores in both groups. |  | 28 days | 
| Number of patients with improvement in Liver severity scores in both groups. |  | 60 days | 
| Number of patients with improvement in Liver severity scores in both groups. |  | 3 months | 
| Number of patients with development of adverse events in both groups in both groups. |  | 28 days | 
| Number of patients with development of adverse events in both groups in both groups. |  | 2 months | 
| Number of patients with development of adverse events in both groups in both groups. |  | 3 Months | 
| Number of patients who will develop esophageal variceal bleeding in both groups |  | 28 days | 
| Number of patients who will develop esophageal variceal bleeding in both groups |  | 2 Months | 
| Number of patients who will develop esophageal variceal bleeding in both groups |  | 3 Months | 
| Development of complications in both groups | AKI,Pneumonia,SBP and other infections | 28 days | 
| Development of complications in both groups | AKI,Pneumonia,SBP and other infections | 2 months | 
| Development of complications in both groups | AKI,Pneumonia,SBP and other infections | 3 months | 
| Mortality in both groups |  | 2 months | 
| Mortality in both groups |  | 3 months |