Primary Prophylaxis for Variceal Bleed in Biliary Atresia
- Conditions
- Portal Hypertension, Biliary Atresia
- Interventions
- Other: Placebo
- Registration Number
- NCT04494763
- Lead Sponsor
- Institute of Liver and Biliary Sciences, India
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 92
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).
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Propanolol 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 Placebo Placebo Placebo in a similar manner
- Primary Outcome Measures
Name Time Method Bleeding free survival over 18 months follow-up 18 months
- Secondary Outcome Measures
Name Time Method Progression, persistence or regression of esophageal varices 18 months Overall survival 18 months Progression, persistence or regression of gastric varices 18 months Progression, persistence or regression of portal hypertensive gastropathy 18 months
Trial Locations
- Locations (1)
Institute of Liver and Biliary Sciences
🇮🇳New Delhi, Delhi, India