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

NCT00294684 | Completed Results DMC

• 2 other identifiers: CHILDREN (START) (IND)U01DK062456
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 14

Brief 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. 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).

Conditions

Biliary Atresia

Keywords

biliary atresia; hepatoportoenterostomy; corticosteroids

Outcome Measures

Primary Outcomes (1)

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

  Measurements will be made at 6 months after portoenterostomy

Secondary Outcomes (8)

• Survival With Native Liver at 24 Months of Age

  Measurements will be made at 24 months of age

• Serum Total Bilirubin Concentration

  Measurements will be made at 3 months after portoenterostomy

• Total Bilirubin Concentration at 12 Months

  12 Months post HPE

• Total Bilirubin Concentration at 24 Months of Age

  At 24 Months of Age

• Weight Z-Score

  HPE until 24 months of age

Other Outcomes (8)

• Serum Biomarkers of Sufficiency of Fat-soluble Vitamins - Vitamin E

  24 Months

• Serum Biomarkers of Sufficiency of Fat-soluble Vitamins - Vitamin K

  24 Months

• Serum Biomarkers of Sufficiency of Fat-soluble Vitamins - Vitamin D

  24 Months

Study Arms (2)

Corticosteroids

EXPERIMENTAL

Drug: Corticosteroids

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Corticosteroids DRUG

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

Also known as: methylprednisolone, prednisolone

Corticosteroids

Placebo DRUG

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

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (14)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California at San Francisco

San Francisco, California, 94143, United States

Location

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

Children's Hospital of Atlanta - Emory University

Atlanta, Georgia, 30322, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Riley Children's Hospital

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins School of Medicine

Baltimore, Maryland, 21287, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital at Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Texas Children's Hospital/Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Children's Hospital and Regional Medical Center

Seattle, Washington, 98105, United States

Location

Related Publications (6)

• 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.

  PMID: 24794368 RESULT

• 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.

  PMID: 30244988 DERIVED

• 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.

  PMID: 29519540 DERIVED

• 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.

  PMID: 26725209 DERIVED

• 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.

  PMID: 25419594 DERIVED

• 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.

  PMID: 22891232 DERIVED

Related Links

• Children Liver Disease Research and Education Network (ChiLDREN)

MeSH Terms

Conditions

Biliary Atresia

Interventions

Adrenal Cortex Hormones; Methylprednisolone; Prednisolone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Ed Doo
• Organization: NIDDK

dooe@niddk.gov

Study Officials

• Ronald Sokol, MD

  Children's Hospital Colorado

  STUDY CHAIR

• Ed Doo, MD

  National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

  STUDY DIRECTOR

• John Magee, MD

  University of Michigan Medical Center, Ann Arbor

  PRINCIPAL INVESTIGATOR

• Averell Sherker, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2006
• First Posted: February 22, 2006
• Study Start: November 1, 2005
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: October 22, 2019
• Results First Posted: May 5, 2017

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Within six months of the publication date for the primary outcome publication or within two years of the date that the database is locked for analysis, whichever occurs first.

Locations

US (14)