Cara L Mack1, Cathie Spino2, Estella M Alonso3, Jorge A Bezerra4, Jeffrey Moore2, Catherine Goodhue5, Vicky L Ng6, Saul J Karpen7, Veena Venkat8, Kathleen M Loomes9, Kasper Wang5, Averell H Sherker10, John C Magee2, Ronald J Sokol1. 1. Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO. 2. University of Michigan, Ann Arbor, MI. 3. Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL. 4. Cincinnati Children's Hospital Medical Center, Cincinnati, OH. 5. Children's Hospital Los Angeles, Los Angeles, CA. 6. The Hospital for Sick Children, University of Toronto, Toronto, Canada. 7. Emory University School of Medicine, Atlanta, GA. 8. Children's Hospital of Pittsburgh, Pittsburgh. 9. Children's Hospital of Philadelphia, Philadelphia, PA. 10. National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MA.
Abstract
OBJECTIVES:Biliary atresia (BA) is a progressive neonatal fibroinflammatory cholangiopathy. We hypothesized that intravenous immunoglobulin (IVIg) would be safe, feasible, acceptable, and efficacious for the treatment of BA. The primary objective of this study was to establish the feasibility, acceptability, and safety profile of IVIg administration after hepatoportoenterostomy (HPE) in BA. The secondary objective was to determine the treatment efficacy of IVIg based on good bile drainage and survival with the native liver. METHODS: A multicenter, prospective, open-labeled, phase I/IIA trial of IVIg was conducted, with 1 g/kg/dose of IVIg infused at 3-5, 30, and 60 days post-HPE, and subjects followed for 360 days post-HPE. Twenty-nine participants completed the study. RESULTS: Administration of IVIg infusions was feasible and acceptable in 79%. None of the serious adverse events (SAEs) were directly related to IVIg infusions; however, 90% of participants had an SAE. Compared with a historical placebo-arm group, there was no significant increase in the proportion of IVIg participants with a serum total bilirubin <1.5 mg/dL at 90, 180, or 360 days post-HPE. Survival with the native liver in the IVIg participants showed no significant benefit over the historical placebo arm, with a difference at 360 days of -11.9% (IVIg: 58.6%, placebo: 70.5%; 90% UCB: 2.1%; P > 0.05). CONCLUSIONS: Although IVIg infusions in infants with BA post-HPE were feasible, acceptable and safe, there was no trend to lower bilirubin levels or improved 360-day survival with the native liver. CLINICAL TRIAL: Safety Study of Intravenous Immunoglobulin Post-Portoenterostomy in Biliary Atresia; #NCT01854827.
RCT Entities:
OBJECTIVES:Biliary atresia (BA) is a progressive neonatal fibroinflammatory cholangiopathy. We hypothesized that intravenous immunoglobulin (IVIg) would be safe, feasible, acceptable, and efficacious for the treatment of BA. The primary objective of this study was to establish the feasibility, acceptability, and safety profile of IVIg administration after hepatoportoenterostomy (HPE) in BA. The secondary objective was to determine the treatment efficacy of IVIg based on good bile drainage and survival with the native liver. METHODS: A multicenter, prospective, open-labeled, phase I/IIA trial of IVIg was conducted, with 1 g/kg/dose of IVIg infused at 3-5, 30, and 60 days post-HPE, and subjects followed for 360 days post-HPE. Twenty-nine participants completed the study. RESULTS: Administration of IVIg infusions was feasible and acceptable in 79%. None of the serious adverse events (SAEs) were directly related to IVIg infusions; however, 90% of participants had an SAE. Compared with a historical placebo-arm group, there was no significant increase in the proportion of IVIg participants with a serum total bilirubin <1.5 mg/dL at 90, 180, or 360 days post-HPE. Survival with the native liver in the IVIg participants showed no significant benefit over the historical placebo arm, with a difference at 360 days of -11.9% (IVIg: 58.6%, placebo: 70.5%; 90% UCB: 2.1%; P > 0.05). CONCLUSIONS: Although IVIg infusions in infants with BA post-HPE were feasible, acceptable and safe, there was no trend to lower bilirubin levels or improved 360-day survival with the native liver. CLINICAL TRIAL: Safety Study of Intravenous Immunoglobulin Post-Portoenterostomy in Biliary Atresia; #NCT01854827.
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Authors: Cara L Mack; Rebecca M Tucker; Ronald J Sokol; Frederick M Karrer; Brian L Kotzin; Peter F Whitington; Stephen D Miller Journal: Pediatr Res Date: 2004-05-05 Impact factor: 3.756
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Authors: Sehee Kim; Jeffrey Moore; Estella Alonso; Joseph Bednarek; Jorge A Bezerra; Catherine Goodhue; Saul J Karpen; Kathleen M Loomes; John C Magee; Vicky L Ng; Averell H Sherker; Caroline Smith; Cathie Spino; Veena Venkat; Kasper Wang; Ronald J Sokol; Cara L Mack Journal: Hepatol Commun Date: 2019-03-25
Authors: Veena Venkat; Vicky L Ng; John C Magee; Wen Ye; Kieran Hawthorne; Sanjiv Harpavat; Jean P Molleston; Karen F Murray; Kasper S Wang; Nisreen Soufi; Lee M Bass; Estella M Alonso; Jorge A Bezerra; M Kyle Jensen; Binita M Kamath; Kathleen M Loomes; Cara L Mack; Philip Rosenthal; Benjamin L Shneider; Robert H Squires; Ronald J Sokol; Saul J Karpen Journal: Hepatol Commun Date: 2020-10-03