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

Fontan Circulation Clinical Trial

— IMPROVE-FALD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06324396
• Other study ID #: STUDY00002974
• Status: Recruiting
• Phase: Phase 1
• Start date: March 1, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: Children's Mercy Hospital Kansas City
• Contact: Jonthan Wagner, DO
• Phone: 816-731-7240
• Email: jbwagner[@]cmh.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fontan Circulation
• Liver Diseases
• Univentricular Heart

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Children's Mercy Hospital	Kansas City	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Children's Mercy Hospital Kansas City	Indiana Clinical and Translational Sciences Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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