Efficacy of Nonselective Beta Blocker vs Placebo in Patients With Acute-on-chronic Liver Failure With Small/ no Esophageal Varices
Primary Purpose
Acute on Chronic Liver Failure
Status
Completed
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Carvedilol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute on Chronic Liver Failure
Eligibility Criteria
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
Sites / Locations
- Institute of liver and Biliary Sciences
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Carvedilol
placebo
Arm Description
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
Outcomes
Primary Outcome Measures
Mortality in both groups
Secondary Outcome Measures
Number of patients with development or progression of esophageal varices in both groups.
Number of patients with reduction in hepatic venous pressure gradient (HVPG) in both groups.
Number of patients with regression in esophageal varices in both groups.
Number of patients with improvement in Liver severity scores in both groups.
Number of patients with improvement in Liver severity scores in both groups.
Number of patients with improvement in Liver severity scores in both groups.
Number of patients with development of adverse events in both groups in both groups.
Number of patients with development of adverse events in both groups in both groups.
Number of patients with development of adverse events in both groups in both groups.
Number of patients who will develop esophageal variceal bleeding in both groups
Number of patients who will develop esophageal variceal bleeding in both groups
Number of patients who will develop esophageal variceal bleeding in both groups
Development of complications in both groups
AKI,Pneumonia,SBP and other infections
Development of complications in both groups
AKI,Pneumonia,SBP and other infections
Development of complications in both groups
AKI,Pneumonia,SBP and other infections
Mortality in both groups
Mortality in both groups
Full Information
NCT ID
NCT02583698
First Posted
October 21, 2015
Last Updated
June 1, 2019
Sponsor
Institute of Liver and Biliary Sciences, India
1. Study Identification
Unique Protocol Identification Number
NCT02583698
Brief Title
Efficacy of Nonselective Beta Blocker vs Placebo in Patients With Acute-on-chronic Liver Failure With Small/ no Esophageal Varices
Official Title
Efficacy of Nonselective Beta Blockers vs Placebo in Patients With Acute-on-chronic Liver Failure With Small/ no Esophageal Varices
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
October 1, 2015 (Actual)
Primary Completion Date
July 1, 2017 (Actual)
Study Completion Date
July 1, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Liver and Biliary Sciences, India
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute on Chronic Liver Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
136 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carvedilol
Arm Type
Experimental
Arm Description
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
Arm Title
placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Mortality in both groups
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Number of patients with development or progression of esophageal varices in both groups.
Time Frame
3 Months
Title
Number of patients with reduction in hepatic venous pressure gradient (HVPG) in both groups.
Time Frame
3 Months
Title
Number of patients with regression in esophageal varices in both groups.
Time Frame
3 Months
Title
Number of patients with improvement in Liver severity scores in both groups.
Time Frame
28 days
Title
Number of patients with improvement in Liver severity scores in both groups.
Time Frame
60 days
Title
Number of patients with improvement in Liver severity scores in both groups.
Time Frame
3 months
Title
Number of patients with development of adverse events in both groups in both groups.
Time Frame
28 days
Title
Number of patients with development of adverse events in both groups in both groups.
Time Frame
2 months
Title
Number of patients with development of adverse events in both groups in both groups.
Time Frame
3 Months
Title
Number of patients who will develop esophageal variceal bleeding in both groups
Time Frame
28 days
Title
Number of patients who will develop esophageal variceal bleeding in both groups
Time Frame
2 Months
Title
Number of patients who will develop esophageal variceal bleeding in both groups
Time Frame
3 Months
Title
Development of complications in both groups
Description
AKI,Pneumonia,SBP and other infections
Time Frame
28 days
Title
Development of complications in both groups
Description
AKI,Pneumonia,SBP and other infections
Time Frame
2 months
Title
Development of complications in both groups
Description
AKI,Pneumonia,SBP and other infections
Time Frame
3 months
Title
Mortality in both groups
Time Frame
2 months
Title
Mortality in both groups
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr Sumeet Kainth, MD
Organizational Affiliation
Institute of Liver and Biliary Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of liver and Biliary Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110070
Country
India
12. IPD Sharing Statement
Citations:
PubMed Identifier
31541422
Citation
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.
Results Reference
derived
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Efficacy of Nonselective Beta Blocker vs Placebo in Patients With Acute-on-chronic Liver Failure With Small/ no Esophageal Varices
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