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Biliary AtresiaNCT00294684

A Randomized, Double-Blinded, Placebo-Controlled Trial of Corticosteroid Therapy Following Portoenterostomy

A study testing Corticosteroids in people with Biliary Atresia, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The Children Liver Disease Research and Education Network (ChiLDREN) is conducting a clinical trial to evaluate whether long-term treatment with corticosteroids improves the outcome of the Kasai or gall-bladder Kasai in infants with biliary atresia. Read more about this study

Who is it for?
Ages Up to 6 months
Conditions the study is for
Biliary Atresia
What is being tested?
Corticosteroids
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
141 participants
Where
14 sitesUnited States
Study dates
Nov 2005to Jan 2013
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Up to 6 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Portoenterostomy or gall bladder Kasai operation for biliary atresia within the previous 72 hours
  • Post-conception age ≥ 36 weeks
  • Weight at enrolment ≥ 2000 gm
  • Written informed consent to participate in the study obtained prior to or within 72 hours of completion of portoenterostomy. (Note: Families of potential subjects may be approached prior to the portoenterostomy.)

Who cannot join

  • Known immunodeficiency
  • Diabetes mellitus
  • Presence of significant systemic hypertension for age (persistent systolic blood pressure ≥112 mmHg)
  • A serum indirect (unconjugated) bilirubin ≥ 5 mg/dL for infants under 4 weeks of age or ≥ 7 mg/dL for infants between 4 and 8 weeks of age
  • Known sensitivity to corticosteroids
  • Documented bacteremia or other tissue infection which is felt to be clinically relevant
Show all 12Show fewer
  • Known congenital infection or disease with herpes simplex virus, toxoplasmosis, or cytomegalovirus inclusion disease of the liver
  • Infants whose mother is known to have human immunodeficiency virus infection
  • Infants whose mother is known to be HBsAg or hepatitis C virus positive
  • Infants with other severe concurrent illnesses such as neurological, cardiovascular, pulmonary, metabolic, endocrine, and renal disorders that would interfere with the conduct and results of the study
  • Any other clinical condition that is a contraindication to the use of corticosteroid (e.g., bowel perforation)
  • Infants who have received the live attenuated rotavirus vaccine (e.g., Rotateq) within 5 days prior to proposed administration of study drug

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites
  • Children's Hospital of Atlanta - Emory University

    Atlanta, Georgia, 30322

  • The Children's Hospital

    Aurora, Colorado, 80045

  • Johns Hopkins School of Medicine

    Baltimore, Maryland, 21287

  • Children's Memorial Hospital

    Chicago, Illinois, 60614

  • Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Texas Children's Hospital/Baylor College of Medicine

    Houston, Texas, 77030

  • Riley Children's Hospital

    Indianapolis, Indiana, 46202

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital at Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • University of California at San Francisco

    San Francisco, California, 94143

  • Children's Hospital and Regional Medical Center

    Seattle, Washington, 98105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Randomized, Double-Blinded, Placebo-Controlled Trial of Corticosteroid Therapy Following Portoenterostomy in Infants With Biliary Atresia

The Children Liver Disease Research and Education Network (ChiLDREN) is conducting a clinical trial to evaluate whether long-term treatment with corticosteroids improves the outcome of the Kasai or gall-bladder Kasai in infants with biliary atresia. In this clinical trial, ChiLDREN is testing whether corticosteroid therapy following the Kasai will improve bile drainage and long term outcome in infants with biliary atresia. Subjects in this trial must start treatment within 72 hours of the Kasai procedure and be part of a prospective study of the natural history of biliary atresia also being conducted by ChiLDREN (http://www.clinicaltrials.gov/ct/show/NCT00061828?order=3).

Read the detailed description

This is a multi-center randomized, double-blinded, placebo-controlled trial to prospectively determine the efficacy of corticosteroids on the outcome of infants with biliary atresia. The trial will be conducted by the NIDDK-funded network of 15 clinical centers comprising the Biliary Children Liver Disease Research and Education Network (ChiLDREN), whose goal is to study the etiology, pathogenesis, diagnosis, and treatment of infants with biliary atresia. For the trial, our overall hypothesis is that therapy with corticosteroids following portoenterostomy (including gall bladder Kasai procedure) will improve bile drainage and long-term outcome in infants with biliary atresia. This hypothesis will be tested through the following specific aims and hypotheses:

Aim 1: To determine whether corticosteroid therapy decreases serum bilirubin concentration after portoenterostomy.

Aim 2: To determine whether corticosteroid treatment after portoenterostomy will improve outcome as defined by survival without transplantation at 24 months of age.

Aim 3: To determine whether corticosteroid treatment after portoenterostomy will improve growth of infants with biliary atresia.

Aim 4: To determine whether corticosteroid treatment improves biochemical indicators of each of the fat-soluble vitamins after supplementation with standard doses.

Aim 5: To determine whether corticosteroid treatment after portoenterostomy will decrease the incidence of persistent ascites or ascites that requires medical treatment.

The significance of the proposed trial is that it will determine whether corticosteroids are an effective medical treatment to improve bile drainage and long-term outcome, and whether its use reduces the need for liver transplantation in infants with biliary atresia.

Subjects will be recruited from patients enrolled in the ChiLDREN prospective observational database study who undergo portoenterostomy or portochelecystostomy (gall bladder Kasai) for biliary atresia.

The Primary outcome measure is the percentage of patients with serum total bilirubin <1.5 mg/dL and with native liver at 6 months after portoenterostomy.

Secondary outcome measures are:

  1. Serum total bilirubin concentration (and also at 3 months after portoenterostomy)
  2. Survival with native liver at 24 months of age
  3. Growth
  4. Weight for age Z-score (in patients without ascites)
  5. Height for age Z score
  6. Serum biomarkers of sufficiency of fat-soluble vitamins
  7. Vitamin A: molar ratio of serum retinol/retinol binding protein
  8. Vitamin D: serum level of 25-hydroxy vitamin D
  9. Vitamin E: ratio of serum vitamin E/total lipids
  10. Vitamin K: International Normalized Ratio (INR)
  11. Presence of ascites

All measurements will be made at 12 and 24 months of age (unless noted otherwise):

Conditions
Biliary Atresia
Being tested
Corticosteroids, Placebo
Keywords
biliary atresia, hepatoportoenterostomy, corticosteroids
Medical subject headings
Biliary Atresia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CorticosteroidsDrug

    Also called methylprednisolone, prednisolone

    Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.

    Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop

  • PlaceboDrug

    Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:

    Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop

Study groups in NCT00294684
Study groupRoleWhat they receive
CorticosteroidsExperimentalNot described
Receives: Drug: Corticosteroids
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Percentage of Patients With Serum Total Bilirubin <1.5 mg/dL and With Native Liver at 6 Months After Portoenterostomy

    Measured: Measurements will be made at 6 months after portoenterostomy

Secondary outcomes (8)
  1. Survival With Native Liver at 24 Months of Age

    Measured: Measurements will be made at 24 months of age

  2. Serum Total Bilirubin Concentration

    Measured: Measurements will be made at 3 months after portoenterostomy

  3. Total Bilirubin Concentration at 12 Months

    Measured: 12 Months post HPE

  4. Total Bilirubin Concentration at 24 Months of Age

    Measured: At 24 Months of Age

  5. Weight Z-Score

    weight for age Z-score (in subjects without ascites) over the course of the study

    Measured: HPE until 24 months of age

  6. Height Z-Score

    Height by Age Z-score over the course of the study

    Measured: HPE to age 24 Months

  7. Presence of Ascites at 12 Months

    Measured: 12 Months

  8. Presence of Ascites at 24 Months

    Measured: 24 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2006 (estimated)
  2. Study startNov 2005
  3. Primary completionJan 2013
  4. Study completionJan 2013

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
141 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00294684
Sponsor's protocol ID
CHILDREN (START) (IND)
Other IDs
U01DK062456
Status last verified
Oct 2019
First submitted
21 Feb 2006
Last updated
22 Oct 2019
Data monitoring committee
Yes
Individual data sharing
Yes: Archived dataset will be entered into NIDDK Repository

Publications

  • Bezerra JA, Spino C, Magee JC, Shneider BL, Rosenthal P, Wang KS, Erlichman J, Haber B, Hertel PM, Karpen SJ, Kerkar N, Loomes KM, Molleston JP, Murray KF, Romero R, Schwarz KB, Shepherd R, Suchy FJ, Turmelle YP, Whitington PF, Moore J, Sherker AH, Robuck PR, Sokol RJ; Childhood Liver Disease Research and Education Network (ChiLDREN). Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial. JAMA. 2014 May 7;311(17):1750-9. doi: 10.1001/jama.2014.2623.

    PubMed 24794368
  • Alonso EM, Ye W, Hawthorne K, Venkat V, Loomes KM, Mack CL, Hertel PM, Karpen SJ, Kerkar N, Molleston JP, Murray KF, Romero R, Rosenthal P, Schwarz KB, Shneider BL, Suchy FJ, Turmelle YP, Wang KS, Sherker AH, Sokol RJ, Bezerra JA, Magee JC; ChiLDReN Network. Impact of Steroid Therapy on Early Growth in Infants with Biliary Atresia: The Multicenter Steroids in Biliary Atresia Randomized Trial. J Pediatr. 2018 Nov;202:179-185.e4. doi: 10.1016/j.jpeds.2018.07.002. Epub 2018 Sep 21.

    PubMed 30244988
  • Ng VL, Sorensen LG, Alonso EM, Fredericks EM, Ye W, Moore J, Karpen SJ, Shneider BL, Molleston JP, Bezerra JA, Murray KF, Loomes KM, Rosenthal P, Squires RH, Wang K, Arnon R, Schwarz KB, Turmelle YP, Haber BH, Sherker AH, Magee JC, Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN). Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study. J Pediatr. 2018 May;196:139-147.e3. doi: 10.1016/j.jpeds.2017.12.048. Epub 2018 Mar 5.

    PubMed 29519540
  • Shneider BL, Magee JC, Karpen SJ, Rand EB, Narkewicz MR, Bass LM, Schwarz K, Whitington PF, Bezerra JA, Kerkar N, Haber B, Rosenthal P, Turmelle YP, Molleston JP, Murray KF, Ng VL, Wang KS, Romero R, Squires RH, Arnon R, Sherker AH, Moore J, Ye W, Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN). Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia. J Pediatr. 2016 Mar;170:211-7.e1-2. doi: 10.1016/j.jpeds.2015.11.058. Epub 2015 Dec 24.

    PubMed 26725209
  • Venkat VL, Shneider BL, Magee JC, Turmelle Y, Arnon R, Bezerra JA, Hertel PM, Karpen SJ, Kerkar N, Loomes KM, Molleston J, Murray KF, Ng VL, Raghunathan T, Rosenthal P, Schwartz K, Sherker AH, Sokol RJ, Teckman J, Wang K, Whitington PF, Heubi JE; Childhood Liver Disease Research and Education Network. Total serum bilirubin predicts fat-soluble vitamin deficiency better than serum bile acids in infants with biliary atresia. J Pediatr Gastroenterol Nutr. 2014 Dec;59(6):702-7. doi: 10.1097/MPG.0000000000000547.

    PubMed 25419594
  • Shneider BL, Magee JC, Bezerra JA, Haber B, Karpen SJ, Raghunathan T, Rosenthal P, Schwarz K, Suchy FJ, Kerkar N, Turmelle Y, Whitington PF, Robuck PR, Sokol RJ; Childhood Liver Disease Research Education Network (ChiLDREN). Efficacy of fat-soluble vitamin supplementation in infants with biliary atresia. Pediatrics. 2012 Sep;130(3):e607-14. doi: 10.1542/peds.2011-1423. Epub 2012 Aug 13.

    PubMed 22891232

Questions about this trial

What is this clinical trial studying?

A study testing Corticosteroids in people with Biliary Atresia, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 14 sites in United States.

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 4 inclusion and 12 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: finished, as of the sponsor's last update on 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. 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?

Yes. Results are posted in the registry (first posted 5 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Percentage of Patients With Serum Total Bilirubin <1.5 mg/dL and With Native Liver at 6 Months After Portoenterostomy (time frame: Measurements will be made at 6 months after portoenterostomy). 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 NCT00294684, which also lists 6 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 22 Oct 2019.

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