IMProving DRug Dosing and Outcomes for Single VEntricle Patients With Fontan Associated Liver Disease (IMPROVE-FALD)

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.

Study Overview

• Status: Recruiting
• Conditions: Fontan Circulation
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jonthan Wagner, DO; Phone Number: 816-731-7240; Email: jbwagner@cmh.edu

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Recruiting
      • Children's Mercy Hospital
      • Contact: Jonathan Wagner, DO
      • Principal Investigator: Jonathan Wagner, DO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Assessment Arm; Assessment group will receive a single dose of oral sildenafil and oral pravastatin.	Drug: Sildenafil 10mg oral tablet (participants <20kg), or 20mg oral tablet (participants ≥20kg); A single oral dose of sildenafil will be administered to all study subjects.; Drug: Pravastatin 20 mg oral tablet (ages <13 years), or 40 mg oral tablet (≥14 years); A single oral dose of pravastatin will be administered to all study subjects.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Children's Mercy Hospital Kansas City
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Indiana Clinical and Translational Sciences Institute
• Investigators: Principal Investigator: Jonathan Wagner, DO, Children's Mercy

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 14, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 22, 2024

Study Record Updates

• Last Update Posted (Estimated): January 2, 2026
• Last Update Submitted That Met QC Criteria: December 31, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Fontan; FALD
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Digestive System Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Univentricular Heart; Liver Diseases; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Dosage Forms; Hydrocarbons; Hydrocarbons, Cyclic; Biological Factors; Carbohydrates; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Amides; Purines; Glycoconjugates; Sulfonamides; Sulfones; Toxins, Biological; Piperazines; Sildenafil Citrate; Pravastatin; Tablets; Glycation End Products, Advanced
• Other Study ID Numbers: STUDY00002974; 5T32HD069038 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No