IMProving DRug Dosing and Outcomes for Single VEntricle Patients With Fontan Associated Liver Disease

Phase 1

Recruiting

• Conditions: Fontan Circulation
• Interventions: Drug: Sildenafil 10mg oral tablet (participants <20kg), or 20mg oral tablet (participants ≥20kg); Drug: Pravastatin 20 mg oral tablet (ages <13 years), or 40 mg oral tablet (≥14 years)

• Registration Number: NCT06324396
• Lead Sponsor: Children's Mercy Hospital Kansas City

Brief Summary

This is a single center, open-label, prospective, investigation to quantify the effects liver congestion and fibrosis has on hepatic drug metabolism and transport in children, adolescents, and young adults with Fontan circulation.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-01
• Study First Submitted: 2024-03-14
• Study First Submitted QC: 2024-03-20
• Study First Posted: 2024-03-22
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-17
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• > 8 years
• Status Post Fontan Completion
• Ability to provide informed permission-assent (<18 years) or consent (≥18 years)
• Fasting overnight (~8 hours)

Exclusion Criteria

• Pregnancy
• Non-fasting
• Non-removable metal in body or where magnetic resonance imaging (MRI) is considered unsafe
• Sildenafil and/or Pravastatin therapy within last 2 months
• History of underlying or laboratory evidence of underlying intestinal, metabolic, autoimmune, renal disease that can alter Sildenafil and Pravastatin disposition (absorption, metabolism, distribution, or clearance)
• Pharmacotherapy that interacts with Sildenafil (cytochrome P450 3A4 and P450 3A5 (CYP3A4/5) inducers/inhibitors) and/or Pravastatin (organic anion transporting polypeptide (OATP1B1) inducers/inhibitors)
• Inability to swallow a tablet
• >5X the age-specific upper limit of normal for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total and conjugated bilirubin
• Diarrhea in the last 24 hours *History of solid organ transplantation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Assessment Arm	Pravastatin 20 mg oral tablet (ages <13 years), or 40 mg oral tablet (≥14 years)	Assessment group will receive a single dose of oral sildenafil and oral pravastatin.
Assessment Arm	Sildenafil 10mg oral tablet (participants <20kg), or 20mg oral tablet (participants ≥20kg)	Assessment group will receive a single dose of oral sildenafil and oral pravastatin.

Primary Outcome Measures

Name	Time	Method
Pravastatin concentration as measured by area under the curve (AUC)	2 years	Area under the time-exposure curve (AUC 0-n) for pravastatin as determinants of the dose-exposure relationship.
Sildenafil concentration as measured by area under the curve (AUC)	2 years	Area under the time-exposure curve (AUC 0-n) for sildenafil as determinants of the dose-exposure relationship.

Trial Locations

Locations (1)

Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States