Primary Prophylaxis for Variceal Bleed in Biliary Atresia

NCT04494763 | Unknown DMC

• 1 other identifier: ILBS-PHT-BA01
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

Portal Hypertension, Biliary Atresia

Keywords

Variceal bleed; primary prophylaxis; Biliary atresia

Outcome Measures

Primary Outcomes (1)

• Bleeding free survival over 18 months follow-up

  18 months

Secondary Outcomes (15)

• Progression, persistence or regression of esophageal varices

  3 months

• Progression, persistence or regression of gastric varices

  3 months

• Progression, persistence or regression of portal hypertensive gastropathy

  3 months

• Progression, persistence or regression of esophageal varices

  6 months

• Progression, persistence or regression of gastric varices

  6 months

Study Arms (2)

Propanolol

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Placebo in a similar manner

Other: Placebo

Interventions

Propanolol DRUG

Non-selective Beta-blocker

Propanolol

Placebo OTHER

Inactive drug

Placebo

Eligibility Criteria

• Age: 6 Months - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver and Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

RECRUITING

Related Publications (9)

• Duche M, Ducot B, Ackermann O, Guerin F, Jacquemin E, Bernard O. Portal hypertension in children: High-risk varices, primary prophylaxis and consequences of bleeding. J Hepatol. 2017 Feb;66(2):320-327. doi: 10.1016/j.jhep.2016.09.006. Epub 2016 Sep 20.

  PMID: 27663417 BACKGROUND

• Fagundes ED, Ferreira AR, Roquete ML, Penna FJ, Goulart EM, Figueiredo Filho PP, Bittencourt PF, Carvalho SD, Albuquerque W. Clinical and laboratory predictors of esophageal varices in children and adolescents with portal hypertension syndrome. J Pediatr Gastroenterol Nutr. 2008 Feb;46(2):178-83. doi: 10.1097/MPG.0b013e318156ff07.

  PMID: 18223377 BACKGROUND

• Poddar U, Thapa BR, Rao KL, Singh K. Etiological spectrum of esophageal varices due to portal hypertension in Indian children: is it different from the West? J Gastroenterol Hepatol. 2008 Sep;23(9):1354-7. doi: 10.1111/j.1440-1746.2007.05102.x. Epub 2007 Aug 6.

  PMID: 17683492 BACKGROUND

• Zargar SA, Javid G, Khan BA, Yattoo GN, Shah AH, Gulzar GM, Singh J, Rehman BU, Din Z. Endoscopic ligation compared with sclerotherapy for bleeding esophageal varices in children with extrahepatic portal venous obstruction. Hepatology. 2002 Sep;36(3):666-72. doi: 10.1053/jhep.2002.35278.

  PMID: 12198659 BACKGROUND

• Zargar SA, Yattoo GN, Javid G, Khan BA, Shah AH, Shah NA, Gulzar GM, Singh J, Shafi HM. Fifteen-year follow up of endoscopic injection sclerotherapy in children with extrahepatic portal venous obstruction. J Gastroenterol Hepatol. 2004 Feb;19(2):139-45. doi: 10.1111/j.1440-1746.2004.03224.x.

  PMID: 14731122 BACKGROUND

• Duche M, Ducot B, Tournay E, Fabre M, Cohen J, Jacquemin E, Bernard O. Prognostic value of endoscopy in children with biliary atresia at risk for early development of varices and bleeding. Gastroenterology. 2010 Dec;139(6):1952-60. doi: 10.1053/j.gastro.2010.07.004. Epub 2010 Jul 14.

  PMID: 20637201 BACKGROUND

• Duche M, Ducot B, Ackermann O, Baujard C, Chevret L, Frank-Soltysiak M, Jacquemin E, Bernard O. Experience with endoscopic management of high-risk gastroesophageal varices, with and without bleeding, in children with biliary atresia. Gastroenterology. 2013 Oct;145(4):801-7. doi: 10.1053/j.gastro.2013.06.022. Epub 2013 Jun 19.

  PMID: 23792202 BACKGROUND

• Shashidhar H, Langhans N, Grand RJ. Propranolol in prevention of portal hypertensive hemorrhage in children: a pilot study. J Pediatr Gastroenterol Nutr. 1999 Jul;29(1):12-7. doi: 10.1097/00005176-199907000-00007.

  PMID: 10400097 BACKGROUND

• Drolet BA, Frommelt PC, Chamlin SL, Haggstrom A, Bauman NM, Chiu YE, Chun RH, Garzon MC, Holland KE, Liberman L, MacLellan-Tobert S, Mancini AJ, Metry D, Puttgen KB, Seefeldt M, Sidbury R, Ward KM, Blei F, Baselga E, Cassidy L, Darrow DH, Joachim S, Kwon EK, Martin K, Perkins J, Siegel DH, Boucek RJ, Frieden IJ. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics. 2013 Jan;131(1):128-40. doi: 10.1542/peds.2012-1691. Epub 2012 Dec 24.

  PMID: 23266923 BACKGROUND

MeSH Terms

Conditions

Hypertension, Portal; Biliary Atresia

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Rajeev Khanna, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rajeev Khanna, MD

CONTACT

+919654246963; drrajeev_khanna@rediffmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label Randomized controlled trial - Block randomization

Study Record Dates

• First Submitted: April 19, 2018
• First Posted: July 31, 2020
• Study Start: August 15, 2020
• Primary Completion: June 13, 2022
• Study Completion: June 15, 2022
• Last Updated: March 18, 2021

Record last verified: 2020-07

Locations

IN (1)