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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00294684
First received: February 21, 2006
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

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).


Condition Intervention
Biliary Atresia
Drug: Corticosteroids
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blinded, Placebo-Controlled Trial of Corticosteroid Therapy Following Portoenterostomy in Infants With Biliary Atresia

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival with native liver at 24 months of age [ Time Frame: Measurements will be made at 24 months of age ] [ Designated as safety issue: No ]
  • Serum total bilirubin concentration [ Time Frame: Measurements will be made at 3 months after portoenterostomy and at 12 and 24 months of age ] [ Designated as safety issue: No ]
  • Growth [ Time Frame: Measurements will be made at 12 and 24 months of age ] [ Designated as safety issue: No ]
    weight for age Z-score (in subjects without ascites) and height for age Z-score

  • Serum biomarkers of sufficiency of fat-soluble vitamins [ Time Frame: Measurements will be made at 12 and 24 months of age ] [ Designated as safety issue: No ]
    Vitamin A: molar ratio of serum retinol/retinol-binding protein; Vitamin D: serum level of 25-hydroxy vitamin D; Vitamin E: ratio of serum vitamin E/total lipids; Vitamin K: INR

  • Presence of ascites [ Time Frame: Measurements will be made at 12 and 24 months of age ] [ Designated as safety issue: No ]

Enrollment: 140
Study Start Date: November 2005
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Corticosteroids Drug: Corticosteroids

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

Other Names:
  • methylprednisolone
  • prednisolone
Placebo Comparator: Placebo Drug: Placebo

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


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 6 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.)

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00294684

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
University of California at San Francisco
San Francisco, California, United States, 94143
United States, Colorado
The Children's Hospital
Aurora, Colorado, United States, 80045
United States, Georgia
Children's Hospital of Atlanta - Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Indiana
Riley Children's Hospital
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins School of Medicine
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington University School of Medicine
St Louis, Missouri, United States, 63110
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Ohio
Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital at Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Texas Children's Hospital/Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Children's Hospital and Regional Medical Center
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Investigators
Study Chair: Ronald Sokol, MD Children's Hospital Colorado
Study Director: Ed Doo, MD National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
Principal Investigator: John Magee, MD University of Michigan Medical Center, Ann Arbor
Study Director: Averell Sherker, MD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00294684     History of Changes
Other Study ID Numbers: CHILDREN (START) (IND)
Study First Received: February 21, 2006
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
biliary atresia
hepatoportoenterostomy
corticosteroids

Additional relevant MeSH terms:
Biliary Atresia
Bile Duct Diseases
Biliary Tract Diseases
Congenital Abnormalities
Digestive System Abnormalities
Digestive System Diseases
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014