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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04494763
Recruitment Status : Unknown
Verified July 2020 by Institute of Liver and Biliary Sciences, India.
Recruitment status was:  Recruiting
First Posted : July 31, 2020
Last Update Posted : March 18, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Portal Hypertension, Biliary Atresia Drug: Propanolol Other: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Open label Randomized controlled trial - Block randomization
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Propanolol for Primary Prophylaxis for Variceal Bleed in Biliary Atresia - An Open Label Randomized Controlled Study
Actual Study Start Date : August 15, 2020
Estimated Primary Completion Date : June 13, 2022
Estimated Study Completion Date : June 15, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

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




Primary Outcome Measures :
  1. Bleeding free survival over 18 months follow-up [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. Progression, persistence or regression of esophageal varices [ Time Frame: 3 months ]
  2. Progression, persistence or regression of gastric varices [ Time Frame: 3 months ]
  3. Progression, persistence or regression of portal hypertensive gastropathy [ Time Frame: 3 months ]
  4. Progression, persistence or regression of esophageal varices [ Time Frame: 6 months ]
  5. Progression, persistence or regression of gastric varices [ Time Frame: 6 months ]
  6. Progression, persistence or regression of portal hypertensive gastropathy [ Time Frame: 6 months ]
  7. Progression, persistence or regression of esophageal varices [ Time Frame: 12 months ]
  8. Progression, persistence or regression of gastric varices [ Time Frame: 12 months ]
  9. Progression, persistence or regression of portal hypertensive gastropathy [ Time Frame: 12 months ]
  10. Progression, persistence or regression of esophageal varices [ Time Frame: 18 months ]
  11. Progression, persistence or regression of gastric varices [ Time Frame: 18 months ]
  12. Progression, persistence or regression of portal hypertensive gastropathy [ Time Frame: 18 months ]
  13. Overall survival [ Time Frame: 6 months ]
  14. Overall survival [ Time Frame: 12 months ]
  15. Overall survival [ Time Frame: 18 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04494763


Contacts
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Contact: Rajeev Khanna, MD +919654246963 drrajeev_khanna@rediffmail.com

Locations
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India
Institute of Liver and Biliary Sciences Recruiting
New Delhi, Delhi, India, 110070
Contact: Rajeev Khanna, MD    +919654246963    drrajeev_khanna@rediffmail.com   
Contact: Ankit Bhardwaj, MD    +9146300000    bhardwaj.ankit3@gmail.com   
Sponsors and Collaborators
Institute of Liver and Biliary Sciences, India
Investigators
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Principal Investigator: Rajeev Khanna, MD Associate Professor, Pediatric Hepatology, Institute of Liver and Biliary Sciences
Publications:

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Responsible Party: Institute of Liver and Biliary Sciences, India
ClinicalTrials.gov Identifier: NCT04494763    
Other Study ID Numbers: ILBS-PHT-BA01
First Posted: July 31, 2020    Key Record Dates
Last Update Posted: March 18, 2021
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Endoscopic details of the patients on propanolol or placebo

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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
Keywords provided by Institute of Liver and Biliary Sciences, India:
Variceal bleed
primary prophylaxis
Biliary atresia
Additional relevant MeSH terms:
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Hypertension, Portal
Biliary Atresia
Liver Diseases
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Abnormalities
Congenital Abnormalities
Propranolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents