Primary Prophylaxis for Variceal Bleed in Biliary Atresia (BA-BB)

March 17, 2021 updated by: Institute of Liver and Biliary Sciences, India

Propanolol for Primary Prophylaxis for Variceal Bleed in Biliary Atresia - An Open Label Randomized Controlled Study

Biliary atresia is the commonest etiology of neonatal cholestasis and is the most common indication for pediatric liver transplantation world-wide. Kasai-portoenterostomy (KPE) is the operative procedure of choice which helps in restoration of biliary flow and preventing rapid progression of fibrosis. Only 50-60% of infants have a successful surgery in terms of normalization of bilirubin (<2 mg/dL) after 3 months. Remaining 40-50% have rapid progression of PHT and eventual decompensation. Additionally, around 50-70% of infants with successful KPE have 1 or more episodes of cholangitis, and the severe ones if left untreated lead to progressive portal hypertension. Moreover in Indian setting a significant number of infants with biliary atresia reach late when the KPE is not feasible, and this group develops very rapid PHT and decompensation. Hence, overall around 70-80% of infants and children develop PHT within 5 years of age. Variceal bleed has been shown to be an important determinant of survival in infants with high bilirubin. Usage of beta-blockers in adult cirrhotics has been shown to reduce the progression of varices and incidence of variceal bleed. Although many pediatric hepatology centers worldwide use beta-blockers, there has been no controlled trial specifically to address this issue in children with biliary atresia. So, we planned this study to evaluate the efficacy of beta-blockers as primary prophylaxis for prevention of variceal bleed in biliary atresia children.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

(a) Aim and Objectives:

Aim: To study the effect of beta-blockers for primary prophylaxis of variceal bleed in infants and children with biliary atresia.

Primary objective: Bleeding free survival over 18 months FU

Secondary objectives:

(i) Progression, persistence or regression of esophageal and gastric varices, and portal hypertensive gastropathy over 3, 6, 12 and 18 months FU

(ii) Overall survival at 18 months FU

(b) Methodology: This will be an open label randomized controlled study where infants and children with biliary atresia from 6 months to 5 years fulfilling inclusion and exclusion criteria will be enrolled to receive propanolol or placebo for a duration of 18 months or till the occurrence of variceal bleed.

i. Study design: Open label randomized controlled study with stratified randomization.

ii. Intervention: Beta-blocker (Propanolol) versus placebo.

iii. Study period: 1.5 years

iv. Study population: Infants and children from 6 months to 5 years of age with Biliary atresia fulfilling the inclusion and exclusion criteria.

(c) Expected outcome of the project: Beta-blockers reduce the incidence of variceal bleed in infants and children with biliary atresia.

Study Type

Interventional

Enrollment (Anticipated)

92

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 5 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: Infants and children with biliary atresia from 6 months to 5 years of age fulfilling either of the following conditions:

i. With unsuccessful Kasai portoenterostomy procedure with a bilirubin >2 mg/dL, or ii. Who did not underwent Kasai portoenterostomy, or iii. With successful Kasai portoenterostomy procedure with a bilirubin <2 mg/dL, but with features of portal hypertension i.e. clinical splenomegaly and/or thrombocytopenia (platelets < 1,00,000/mm3).

Exclusion Criteria:

i. History suggestive of hyper-reactive airway disease. ii. Congestive heart failure iii. Any degree of heart block (I,, II, III) iv. Infants and children already on beta-blockers in last 4 weeks. v. Portal vein atresia or thrombosis. vi. History of variceal bleed. vii. Infants and children on prophylactic or therapeutic endotherapy (band ligation or sclerotherapy).

viii. Potential liver transplant within 1 month.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Propanolol
Dose: 1 to 8 mg/kg/day in 1 to 2 divided doses adjusted to achieve target reduction in resting heart rate by 25% from baseline Frequency: once to Twice daily Route of Administration: Oral Duration: 18 months
Drug: Propanolol
Non-selective Beta-blocker
Placebo Comparator: Placebo
Placebo in a similar manner
Other: Placebo
Inactive drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Bleeding free survival over 18 months follow-up
Time Frame: 18 months
18 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 12 months
12 months
Overall survival
Time Frame: 18 months
18 months
Overall survival
Time Frame: 6 months
6 months
Progression, persistence or regression of esophageal varices
Time Frame: 3 months
3 months
Progression, persistence or regression of gastric varices
Time Frame: 3 months
3 months
Progression, persistence or regression of portal hypertensive gastropathy
Time Frame: 3 months
3 months
Progression, persistence or regression of esophageal varices
Time Frame: 6 months
6 months
Progression, persistence or regression of gastric varices
Time Frame: 6 months
6 months
Progression, persistence or regression of portal hypertensive gastropathy
Time Frame: 6 months
6 months
Progression, persistence or regression of esophageal varices
Time Frame: 12 months
12 months
Progression, persistence or regression of gastric varices
Time Frame: 12 months
12 months
Progression, persistence or regression of portal hypertensive gastropathy
Time Frame: 12 months
12 months
Progression, persistence or regression of esophageal varices
Time Frame: 18 months
18 months
Progression, persistence or regression of gastric varices
Time Frame: 18 months
18 months
Progression, persistence or regression of portal hypertensive gastropathy
Time Frame: 18 months
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Liver and Biliary Sciences, India

Investigators

  • Principal Investigator: Rajeev Khanna, MD, Associate Professor, Pediatric Hepatology, Institute of Liver and Biliary Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 15, 2020

Primary Completion (Anticipated)

June 13, 2022

Study Completion (Anticipated)

June 15, 2022

Study Registration Dates

First Submitted

April 19, 2018

First Submitted That Met QC Criteria

July 30, 2020

First Posted (Actual)

July 31, 2020

Study Record Updates

Last Update Posted (Actual)

March 18, 2021

Last Update Submitted That Met QC Criteria

March 17, 2021

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ILBS-PHT-BA01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

Endoscopic details of the patients on propanolol or placebo

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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