Portal Hypertension, Biliary AtresiaBA-BBNCT04494763
Primary Prophylaxis for Variceal Bleed in Biliary Atresia
A study testing Propanolol in people with Portal Hypertension, Biliary Atresia, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 5 years
- Conditions the study is for
- Portal Hypertension, Biliary Atresia
- What is being tested?
- Propanolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 1 siteIndia
- Study dates
- 15 Aug 2020to 15 Jun 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
None listed.
Who cannot join
- 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).
- Potential liver transplant within 1 month.
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Institute of Liver and Biliary Sciences
New Delhi, National Capital Territory of Delhi, 110070
Rajeev Khanna, MD, +919654246963, drrajeev_khanna@rediffmail.com
Ankit Bhardwaj, MD, +9146300000, bhardwaj.ankit3@gmail.com
About this study
Official title: Propanolol for Primary Prophylaxis for Variceal Bleed in Biliary Atresia - An Open Label Randomized Controlled Study
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.
Read the 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.
- 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
- Being tested
- Propanolol, Placebo
- Keywords
- Variceal bleed, primary prophylaxis, Biliary atresia
- Medical subject headings
- Hypertension, Portal, Biliary Atresia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropanololDrug
Non-selective Beta-blocker
PlaceboOther
Inactive drug
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Propanolol |
| Placebo | Placebo comparator | Placebo in a similar manner Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bleeding free survival over 18 months follow-up
Measured: 18 months
Secondary outcomes (15)
Progression, persistence or regression of esophageal varices
Measured: 3 months
Progression, persistence or regression of gastric varices
Measured: 3 months
Progression, persistence or regression of portal hypertensive gastropathy
Measured: 3 months
Progression, persistence or regression of esophageal varices
Measured: 6 months
Progression, persistence or regression of gastric varices
Measured: 6 months
Progression, persistence or regression of portal hypertensive gastropathy
Measured: 6 months
Progression, persistence or regression of esophageal varices
Measured: 12 months
Progression, persistence or regression of gastric varices
Measured: 12 months
Progression, persistence or regression of portal hypertensive gastropathy
Measured: 12 months
Progression, persistence or regression of esophageal varices
Measured: 18 months
Progression, persistence or regression of gastric varices
Measured: 18 months
Progression, persistence or regression of portal hypertensive gastropathy
Measured: 18 months
Overall survival
Measured: 6 months
Overall survival
Measured: 12 months
Overall survival
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2020
- Study start15 Aug 2020
- Primary completion13 Jun 2022 (estimated)
- Study completion15 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Portal Hypertension, Biliary AtresiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Open label Randomized controlled trial - Block randomization
- Masking
- None (open label)
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rajeev Khanna, MD, Principal investigator, Associate Professor, Pediatric Hepatology, Institute of Liver and Biliary Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04494763
- Sponsor's protocol ID
- ILBS-PHT-BA01
- Acronym
- BA-BB
- Status last verified
- Jul 2020
- First submitted
- 19 Apr 2018
- Last updated
- 18 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Endoscopic details of the patients on propanolol or placebo
Publications
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.
PubMed 27663417Fagundes 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.
PubMed 18223377Poddar 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.
PubMed 17683492Zargar 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.
PubMed 12198659Zargar 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.
PubMed 14731122Duche 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.
PubMed 20637201Duche 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.
PubMed 23792202Shashidhar 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.
PubMed 10400097Drolet 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.
PubMed 23266923
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Propanolol for Primary Prophylaxis for Variceal Bleed in Biliary Atresia - An Open Label Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT04494763
- Acronym / sponsor ID
- BA-BB / ILBS-PHT-BA01
- Conditions
- Portal Hypertension, Biliary Atresia
- Keywords
- Variceal bleed, primary prophylaxis, Biliary atresia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 15 Aug 2020 (actual)
- Primary completion
- 13 Jun 2022 (estimated)
- Study completion
- 15 Jun 2022 (estimated)
- First posted
- 31 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open label Randomized controlled trial - Block randomization
| Arm | Type | Receives |
|---|---|---|
| Propanolol | Experimental | Drug: PropanololDose: 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 comparator | Other: PlaceboPlacebo in a similar manner |
Who may qualify
- Ages
- 6 months to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (0 listed)
Key exclusion criteria (2 listed)
- 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).
- Potential liver transplant within 1 month.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PropanololNon-selective Beta-blocker | Drug | Propanolol |
| PlaceboInactive drug | Other | Placebo |
Primary outcome
Bleeding free survival over 18 months follow-up
Time frame: 18 months
15 secondary outcomes
Progression, persistence or regression of esophageal varices
Time frame: 3 months
Progression, persistence or regression of gastric varices
Time frame: 3 months
Progression, persistence or regression of portal hypertensive gastropathy
Time frame: 3 months
Progression, persistence or regression of esophageal varices
Time frame: 6 months
Progression, persistence or regression of gastric varices
Time frame: 6 months
Progression, persistence or regression of portal hypertensive gastropathy
Time frame: 6 months
Progression, persistence or regression of esophageal varices
Time frame: 12 months
Progression, persistence or regression of gastric varices
Time frame: 12 months
Progression, persistence or regression of portal hypertensive gastropathy
Time frame: 12 months
Progression, persistence or regression of esophageal varices
Time frame: 18 months
Progression, persistence or regression of gastric varices
Time frame: 18 months
Progression, persistence or regression of portal hypertensive gastropathy
Time frame: 18 months
Overall survival
Time frame: 6 months
Overall survival
Time frame: 12 months
Overall survival
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2021.
- Background: PubMed 27663417Duche 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.
- Background: PubMed 18223377Fagundes 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.
- Background: PubMed 17683492Poddar 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.
- Background: PubMed 12198659Zargar 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.
- Background: PubMed 14731122Zargar 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.
- Background: PubMed 20637201Duche 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.
- Background: PubMed 23792202Duche 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.
- Background: PubMed 10400097Shashidhar 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.
- Background: PubMed 23266923Drolet 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.
- Individual participant dataSharing planned: Undecided. Endoscopic details of the patients on propanolol or placebo
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rajeev Khanna, MD principal investigator
Associate Professor, Pediatric Hepatology, Institute of Liver and Biliary Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Propanolol in people with Portal Hypertension, Biliary Atresia, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rajeev Khanna, MD (+919654246963, drrajeev_khanna@rediffmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bleeding free survival over 18 months follow-up (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04494763, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2021.