CirrhosisPhase 3SiFALDNCT03154476
Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
A Phase 3 study testing Sildenafil in people with Cirrhosis and Congenital Heart Disease, run by Mayo Clinic at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis, Congenital Heart Disease
- What is being tested?
- Sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jul 2017to 30 Jun 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All adult Fontan patients who have no contraindications for magnetic resonance imaging (MRI) will be eligible for the study.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: 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.
Read the detailed description
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Conditions
- Cirrhosis, Congenital Heart Disease
- Being tested
- Sildenafil, Placebo
- Medical subject headings
- Fibrosis, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Also called Revatio
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.
PlaceboDrug
Placebo capsules matching study drug
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil | Experimental | 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. Receives: Drug: Sildenafil |
| Placebo | Placebo comparator | Subjects will receive placebo times per day for 12 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE)
Measured using magnetic resonance imaging derived liver stiffness (MRE-LS) reported in kilopascal (kPa).
Measured: Baseline, 12 months (52 weeks), 24 months (104 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2017
- Study start5 Jul 2017
- Primary completion30 Jun 2019
- Study completion30 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Double-blind Placebo-control study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alexander C. Egbe, Mayo Clinic
- Investigators
- Alexander C Egbe, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03154476
- Sponsor's protocol ID
- 16-008985
- Acronym
- SiFALD
- Status last verified
- Jul 2021
- First submitted
- 12 May 2017
- Last updated
- 23 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
- ClinicalTrials.gov ID
- NCT03154476
- Acronym / sponsor ID
- SiFALD / 16-008985
- Conditions
- Cirrhosis, Congenital Heart Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 5 Jul 2017 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 16 May 2017 (actual)
- Results
- Posted 28 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized Double-blind Placebo-control study
| Arm | Type | Receives |
|---|---|---|
| Sildenafil | Experimental | Drug: SildenafilSubjects 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. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects will receive placebo times per day for 12 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All adult Fontan patients who have no contraindications for magnetic resonance imaging (MRI) will be eligible for the study.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SildenafilAlso: RevatioSildenafil 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. | Drug | Sildenafil |
| PlaceboPlacebo capsules matching study drug | Drug | Placebo |
Primary outcome
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander C Egbe principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sildenafil in people with Cirrhosis and Congenital Heart Disease, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) (time frame: Baseline, 12 months (52 weeks), 24 months (104 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2021.