Primary Prophylaxis for Variceal Bleed in Biliary Atresia

NCT ID: NCT04494763

Last Updated: 2021-03-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-15
• Study Completion Date: 2022-06-15

Brief Summary

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.

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.

Conditions

Portal Hypertension, Biliary Atresia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Propanolol

Intervention Type: DRUG

Non-selective Beta-blocker

Placebo

Placebo in a similar manner

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Inactive drug

Interventions

Propanolol

Non-selective Beta-blocker

Intervention Type: DRUG

Placebo

Inactive drug

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Liver and Biliary Sciences, India

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rajeev Khanna, MD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor, Pediatric Hepatology, Institute of Liver and Biliary Sciences

Locations

Institute of Liver and Biliary Sciences

New Delhi, National Capital Territory of Delhi, India

Site Status: RECRUITING

Countries

India

Central Contacts

Rajeev Khanna, MD

Role: CONTACT

drrajeev_khanna@rediffmail.com

+919654246963

Facility Contacts

Rajeev Khanna, MD

Role: primary

drrajeev_khanna@rediffmail.com

+919654246963

Ankit Bhardwaj, MD

Role: backup

bhardwaj.ankit3@gmail.com

+9146300000

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Other Identifiers

ILBS-PHT-BA01

Identifier Type: -

Identifier Source: org_study_id