Clinical trial NCT04494763: Primary Prophylaxis for Variceal Bleed in Biliary Atresia
Official title: Propanolol for Primary Prophylaxis for Variceal Bleed in Biliary Atresia - An Open Label Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Portal Hypertension, Biliary Atresia
Keywords: Variceal bleed
primary prophylaxis
Biliary atresia
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2020-07-31
Enrollment: 92
Sex: ALL
Minimum age (years): 6
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label Randomized controlled trial - Block randomization
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Bleeding free survival over 18 months follow-up
timeFrame: 18 months
Secondary outcomes:
measure: Progression, persistence or regression of esophageal varices
timeFrame: 3 months
measure: Progression, persistence or regression of gastric varices
timeFrame: 3 months
measure: Progression, persistence or regression of portal hypertensive gastropathy
timeFrame: 3 months
measure: Progression, persistence or regression of esophageal varices
timeFrame: 6 months
measure: Progression, persistence or regression of gastric varices
timeFrame: 6 months
measure: Progression, persistence or regression of portal hypertensive gastropathy
timeFrame: 6 months
measure: Progression, persistence or regression of esophageal varices
timeFrame: 12 months
measure: Progression, persistence or regression of gastric varices
timeFrame: 12 months
measure: Progression, persistence or regression of portal hypertensive gastropathy
timeFrame: 12 months
measure: Progression, persistence or regression of esophageal varices
timeFrame: 18 months
measure: Progression, persistence or regression of gastric varices
timeFrame: 18 months
measure: Progression, persistence or regression of portal hypertensive gastropathy
timeFrame: 18 months
measure: Overall survival
timeFrame: 6 months
measure: Overall survival
timeFrame: 12 months
measure: Overall survival
timeFrame: 18 months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver and Biliary Sciences
state: Delhi
Study officials:
affiliation: Associate Professor, Pediatric Hepatology, Institute of Liver and Biliary Sciences
name: Rajeev Khanna, MD
role: PRINCIPAL_INVESTIGATOR
References:
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