Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study (SiFALD)

July 28, 2021 updated by: Alexander C. Egbe, Mayo Clinic

Sildenafil for Fontan Associated Liver Disease (SiFALD) Study

The purpose of this study is to determine if the medication, sildenafil (also known as Revatio), can slow or stop the progression of liver disease in patients who previously had a Fontan operation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

  1. All participants will undergo a baseline liver magnetic resonance elastography. The patients with liver stiffness score >2.5 kiloPascal (KPa) [Normal: ≤2.5 KPa] will be enrolled in the study.
  2. In addition to a baseline liver MRE, all participants will undergo cardiac MRI, transthoracic echocardiogram (TTE), FibroSure® (alpha-2 macroglobulin, haptoglobulin, gamma-glutamyltransferase, bilirubin, apolipoprotein A1, and alanine transaminase), and chemistry panel.
  3. This will be a double blinded placebo control study design. All participants will be randomized 1:1 to sildenafil or placebo for a total of 12 months therapy.
  4. Sildenafil will be initiated at 5 mg 3 times per day for the first week, and titrated to 10 mg 3 times per day for the second week and 20 mg 3 times per day from the 3rd week to the end of the study period. The patients will be required to check their pulse rate and blood pressure daily during the first month of drug therapy. Patient who experience hypotension (blood pressure < 90/50 plus symptoms such as dizziness) during dose titration will be asked to remain on the previous tolerated dose. Patients who cannot tolerate 10 mg 3 times daily will be asked to withdraw from the study and will be asked to continue checking their blood pressure for three days after stopping the medication.
  5. After 12 months (+/- 2 weeks) of therapy, all imaging studies (liver MRE, cardiac MRI, TTE) and blood tests (FibroSure® and chemistry panel) will be repeated. A final liver MRE and FibroSure will be performed at 18 months (+/- 2 weeks) for the participants whose 18 months follow-up still falls within the study period.
  6. Adverse event and compliance monitoring: During the first month of enrollment (initiation and dose titration), adverse events will be collected by subject report and by weekly telephone interview with dedicated research personnel. For the rest of the study period, adverse events will be collected by subject report and by monthly telephone interview with dedicated research personnel. The research personnel will be responsible for sending out the monthly supply of medications and obtaining a count of the remaining number pills as a measure of compliance. All participants will be provided with a pamphlet containing all the side effects of sildenafil, and contact information of research team for reporting any adverse event of concerns about the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • All adult Fontan patients who have no contraindications for magnetic resonance imaging (MRI) will be eligible for the study.

Exclusion criteria:

  • Subjects with implantable pacemakers
  • Residual cardiac lesions (severe ventricular dysfunction, severe atrioventricular valve regurgitation, Fontan baffle or conduit obstruction)
  • Viral hepatitis
  • Severe renal dysfunction
  • History of sildenafil use in the six months prior to study enrollment
  • Ongoing sildenafil therapy
  • Patients currently taking nitrates
  • Hypotension at baseline (BP <90/50 mmHg)
  • Pulmonary veno-occlusive disease
  • Hearing/vision impairment
  • Pulmonary hypertension due to sickle cell disease
  • Women of child-bearing potential with a positive pregnancy test will additionally be excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Sildenafil
Subjects randomized to this arm will receive sildenafil 5 mg 3 times per day for the first week, and titrated to 10 mg 3 times per day for the second week, and 20 mg 3 times per day from the third week to the end of the study period, 12 months.
Drug: Sildenafil
Sildenafil will be initiated at 5 mg 3 times per day for the first week, and titrated to 10 mg 3 times per day for the second week and 20 mg 3 times per day from the third week to the end of the study period, 12 months.
Other Names:
  • Revatio
PLACEBO_COMPARATOR: Placebo
Subjects will receive placebo times per day for 12 months.
Drug: Placebo
Placebo capsules matching study drug

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE)
Time Frame: Baseline, 12 months (52 weeks), 24 months (104 weeks)
Measured using magnetic resonance imaging derived liver stiffness (MRE-LS) reported in kilopascal (kPa).
Baseline, 12 months (52 weeks), 24 months (104 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alexander C Egbe, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 5, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 12, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 12, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 16, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 23, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 28, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16-008985

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The safety of the subject will be monitored throughout the duration of the study. During the first month of enrollment (initiation and dose titration), adverse events will be collected by subject report and by weekly telephone interview with dedicated research personnel. For the rest of the study period, adverse events will be collected by subject report and by monthly telephone interview with dedicated research personnel. All participants will be provided with a pamphlet containing all the side effects of sildenafil, and contact information of research team for reporting any adverse event of concerns about the study.

The patients will be required to check their pulse rate and blood pressure daily during the first month of drug therapy. Patient who experience hypotension (blood pressure < 90/60 plus symptoms such as dizziness) during dose titration will be asked to remain on the previous tolerated dose

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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