Sildenafil for Liver Fibrosis in Adolescents and Adults After Fontan Operation

NCT04908657 | Unknown Phase 4

• 1 other identifier: 201612207MIPA
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Fontan operation is currently the most common procedure performed in patients with single-ventricle physiology. This surgery allows for passive caval blood flow to the pulmonary arteries in the absence of a subpulmonary pump and therefore separating the pulmonary circulation from systemic circulation. However, late hepatic complications such as liver fibrosis, cirrhosis, or even hepatocellular carcinoma are increasingly described in patients with Fontan circulation. The Fontan associated liver disease (FALD) is related to the decreased cardiac output and elevated central venous pressure after Fontan operation. Although the prevalence of FALD is higher than 90% in patients with Fontan circulation. There are no specific medications can reverse the liver fibrosis or prevent the progression of FALD at present. Sildenafil had been used in patients after Fontan operation not only to decrease their pulmonary vascular resistance and central venous pressure, increased systemic cardiac output. Comparing with other oral pulmonary vasodilators, sildenafil is with less possibility of liver toxicity. Therefore, we will conduct a prospective, open-labeled, randomized-controlled study in at least 90 Fontan patients with age \> 12 years receiving follow -up at our institute. These patients will be in accordance with the ratio of 1: 1 distribution randomized into two groups, group 1 will receive sildenafil 20 mg three times daily for 3 years and the group will not receive any pulmonary vasodilator as a control. Patients in both group will receive the examinations of liver fibrosis markers, transient ultrasound elastography (FibroScan), diffusion-weighted magnetic resonance imaging (DW-MRI) and cardiopulmonary function test at baseline, 1 year, 2 years and 3 years after initiating treatment. Comparing the results of two groups, we may further clarify the treatment effect of sildenafil on FALD in patients after Fontan procedure.

Conditions

Liver Fibrosis

Keywords

Fontan operation; liver fibrosis; sildenafil; treatment

Outcome Measures

Primary Outcomes (1)

• Liver MRI

  Intra-voxel incoherent motion (IVIM) imaging

  from baseline to 3 years

Secondary Outcomes (3)

• 6-minute walk test

  from baseline to 3 years

• cardiopulmonary function test

  from baseline to 3 years

• Transient liver elastography

  from baseline to 3 years

Other Outcomes (1)

• pro-brain natriuretic peptide

  from baseline to 3 years

Study Arms (2)

Treatment group

EXPERIMENTAL

treatment group will administrate oral sildenafil 20 mg three times per day for 3 years

Drug: Sildenafil 20 MG

Control group

NO INTERVENTION

the control group will not receive any specific therapy for decreasing the pulmonary vascular resistance

Interventions

Sildenafil 20 MG DRUG

oral sildenafil 20 mg three times per day for 3 years

Treatment group

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients age ≥ 12 years with anatomic and/or functional univentricular heart receive Fontan procedure followed at our institute (including the patients with heart failure or pregnancy).
• Patients without taking organic nitrates and not allergic to Sildenafil.

You may not qualify if:

• The patients cannot safely receive MRI examination, including patients with severe renal dysfunction, or after pacemaker or implantable cardioverter defibrillator implantation.
• Patients having known liver disease (such as viral hepatitis, alcoholic liver disease, etc.) other than FALD.
• Patients are under sildenafil or any pulmonary vasodilator therapy for lowering pulmonary resistance, or have been using any of these medications in recent 3 months.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Department of Pediatrics, National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Chun-Wei Lu, MD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chun-Wei Lu, MD

CONTACT

+886-2-23123456; joey4147@ms7.hinet.net

Tzu-Yin Lee, RN

CONTACT

+886-2-23123456; carollee842006@yahoo.com.tw

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, Randomized Controlled

Study Record Dates

• First Submitted: April 27, 2017
• First Posted: June 1, 2021
• Study Start: July 3, 2017
• Primary Completion: July 1, 2023
• Study Completion: December 31, 2023
• Last Updated: June 8, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)