Overview
The Investigators propose to test the hypothesis that GCSF enhances the clinical outcome of biliary atresia in a multi-institutional Phase 2 trial to prospectively evaluate the safety and efficacy of GCSF in each of the 2 groups of newly diagnosed BA patients: KBA (i.e., Kasai-operated) or NoK (i.e., patients who did not undergo Kasai surgery). Subjects who participate in the trial will be followed for 2 years.
Description
This is a prospective, randomized, multi-institutional trial in KBA and NoK subjects to be conducted under a Food and Drug Administration approved Investigational New Drug application.
The KBA group is composed of just operated Kasai patients with intraoperative liver biopsy-confirmed BA. Their clinical characteristics have been described in the previously completed Phase 1 study under CR00005169 (ie. inclusion and exclusion criteria as described below)
The NoK group will be composed of newly diagnosed BA patients, including the following:
- surgical patients in whom the Kasai was not performed for intraoperative technical reasons or due to advanced liver disease, who also have no option for rescue liver transplantation.
- Unoperated patients whose family refuses surgery or who are not operative candidates
Having met the same inclusion and exclusion criteria as the Kasai KBS group,
- eligible KBA subjects will be randomized to GCSF vs. no-GCSF at the 10 ug/kg/d dose to be given subcutaneously for 3 consecutive daily doses on the third day following the Kasai procedure.
- eligible NoK subjects will be randomized to GCSF vs. no-GCSF at the 10 ug/kg/d dose to be given subcutaneously for 3 consecutive daily doses on the third day following diagnostic liver biopsy.
Eligibility
Inclusion criteria
- preliminary work up for cholestasis suspected or inconclusive diagnosis of BA.
- Serum Direct bilirubin > 2 mg/dl,GGT> 100 U/L
- Male or female infants with a gestational age> 36 weeks
- Admission weight > 2 kg
- Age > 14 days - 180 days at diagnosis
- For Kasai operated subjects, Type 3 or 4 anatomy of BA
- For Kasai operated subjects, cholangiogram (if performed) diagnostic of BA
- Liver biopsy supporting BA diagnosis
Exclusion criteria
- Patients having access to liver transplantation for immediate liver failure
- Prior Kasai patients
- Major cardiac, renal, central nervous system (CNS) malformations
- Intracranial hemorrhage
- History of recent total parenteral nutrition (TPN) use within the last 2 weeks
- Gl tract obstruction
For Kasai-operated subjects: Type 1 or 2 biliary atresia anatomy
7. Current systemic infection
8. WBC > 20,000 cells/uL
9. Platelet count < 20,000 cells/uL or >1 million cells/uL
10. Concurrent respiratory, metabolic, neurological, cardiovascular, metabolic, and renal illness
11. Elevated serum creatinine > 1 mg/dL
12. Purpura fulminans or unexplained vascular thrombosis