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

Children's Mercy Hospital Kansas City

Status and phase

Enrolling

Phase 1

Conditions

Fontan Circulation

Treatments

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

Funder types

Other

NIH

Identifiers

NCT06324396

5T32HD069038 (U.S. NIH Grant/Contract)

STUDY00002974

Details and patient eligibility

About

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.

Enrollment

15 estimated patients

Sex

All

Ages

8+ years old

Volunteers

No Healthy Volunteers

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