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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute on Chronic Liver Failure
• Intervention / Treatment: Drug: Placebo; Drug: Carvedilol

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver and Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Acute on Chronic Liver Failure as per APASL (Asian Pacific Association of Study of Liver Disease) criteria.
2. 18-75 years
3. HVPG ≥ 12 + No/Small Esophageal varices

Exclusion Criteria:

1. Bradycardia (HR < 60/ min)
2. Hypotension
3. Asthma
4. LVF
5. AKI (Acute Kidney Injury), (S.creat >1.5)
6. Refractory ascites
7. SBP (Spontaneous Bacterial Peritonitis)
8. Pregnancy or Lactation
9. Past history of EVL or EST
10. Significant cardio - pulmonary co-morbidity
11. PVT
12. Presence of grades 3-4 hepatic encephalopathy (HE)
13. Patients going for liver transplant in next 12 weeks
14. No consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: Placebo
Experimental: Carvedilol; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India
• Investigators: Principal Investigator: Dr Sumeet Kainth, MD, Institute of Liver and Biliary Sciences

Publications and helpful links

General Publications

• Kumar M, Kainth S, Choudhury A, Maiwall R, Mitra LG, Saluja V, Agarwal PM, Shasthry SM, Jindal A, Bhardwaj A, Kumar G, Sarin SK. Treatment with carvedilol improves survival of patients with acute-on-chronic liver failure: a randomized controlled trial. Hepatol Int. 2019 Nov;13(6):800-813. doi: 10.1007/s12072-019-09986-9. Epub 2019 Sep 20.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: October 21, 2015
• First Submitted That Met QC Criteria: October 21, 2015
• First Posted (Estimate): October 22, 2015

Study Record Updates

• Last Update Posted (Actual): June 4, 2019
• Last Update Submitted That Met QC Criteria: June 1, 2019
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Liver Diseases; Liver Failure, Acute; Esophageal Diseases; Hypertension, Portal; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure; Esophageal and Gastric Varices; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol
• Other Study ID Numbers: ILBS-ACLF-005