N-Acetylcysteine in Biliary Atresia After Kasai Portoenterostomy

• Status: Active, not recruiting
• Trial end date: 2023-10-31
• Target enrollment: 0
• Participant gender: All

Summary

Biliary atresia (BA) is a devastating liver disease of infancy, characterized by bile duct obstruction leading to liver fibrosis, cirrhosis, and eventual need for transplantation in most cases. BA is treated with Kasai portoenterostomy (KP). KPs can achieve bile drainage and improve outcomes. However, even with standard evidence of "good bile flow," bile flow rarely normalizes completely and liver disease continues to progress.

In this study, the investigators test whether intravenous N-acetylcysteine (NAC) can improve bile flow after KP. The rationale is that NAC leads to synthesis of glutathione, which is a powerful stimulator of bile flow. The primary objective is to determine whether NAC normalizes total serum bile acid (TSBA) concentrations within 24 weeks of KP. Achieving normal TSBAs is uncommon with current standard-of-care, and is predicted to be associated with better long-term outcomes. The secondary objectives are to describe how other parameters commonly followed in BA change with NAC therapy, as well as report adverse events occurring with therapy and in the first two years of life. This study follows the "minimax" Phase 2 clinical trial design.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Treatments: Acetylcysteine; N-monoacetylcystine

Criteria

Inclusion Criteria:

1. Age less than or equal to 90 days at time of KP (standard age range in which KPs are performed)

2. BA diagnosis made by intraoperative cholangiography and KP performed at Texas Children's Hospital, Texas Medical Center Campus

3. Legal guardian(s) sign consent after understanding risks and investigational nature of study

Exclusion Criteria:

1. Decompensated liver disease (INR >1.3) despite parenteral Vitamin K administration)

2. KP not performed for any reason (i.e., normal intraoperative cholangiography, or liver found to be too diseased intraoperatively to proceed with KP)

3. Active respiratory infection

4. Renal impairment, as defined by having an eGFR < 60 mL/min/1.73m2 or creatinine clearance < 60 mL/min (https://www.niddk.nih.gov/health-information/communication-programs/nkdep/laboratory- evaluation/glomerular-filtration-rate-calculators/children-conventional-units)

5. Presence of severe concurrent illnesses, such as pulmonary (i.e., bronchopulmonary dysplasia), neurological, cardiovascular, metabolic, endocrine, and renal disorders, which may be congenital or acquired, that would interfere with the conduct and results of the study