AuthorisedTherapeutic confirmatory (Phase III)Patients with functionally single ventricle (FSV - functionally single ventricle) after Fontan operation.
The term "functionally single ventricle" refers to congenital heart defects in which one of the ventricles is not fully developed and/or one of the valves is atresia/hypoplastic as a result, it is not possible to correct the intracardiac defect. Then, there are indications for the Fontan operation, i.e. a palliative procedure - total cavo-pulmonary connection (TCPC).
In patients with a functionally single ventricle, more than one operation is necessary to separate the systemic and pulmonary circulation. As a result of these procedures, Fontan circulation is created, which consists in bypassing the right heart chambers and directing the venous blood to the pulmonary artery. This leads to the removal of the right-to-left shunt and improvement of arterial blood saturation and reduction of volume overload of the systemic ventricle. At the same time, there is an increase in systemic venous pressure and a decrease in cardiac output. Low pulmonary resistance in these patients is crucial for maintaining optimal hemodynamic conditions both at rest and especially during exercise. Even a slight increase in pulmonary resistance leads to reduced pulmonary blood flow, reduced initial depression of a single ventricle, and consequently to reduced cardiac output and worsened exercise tolerance.
Thus, pulmonary resistance in these patients should be not only normal, but also as low as possible to ensure adequate single ventricular filling and adequate cardiac output. There is evidence that patients with Fontan surgery increase pulmonary resistance over time.
The increase in pulmonary resistance in these patients may result from several factors, and above all from the progressive dysfunction of a single systemic ventricle and the lack of a subpulmonary chamber ensuring pulsatile pulmonary flow.
Although the Fontan operation in many patients with an univentricular heart is a very good method of palliative treatment, which undoubtedly extends the survival of children born with this heart defect, it also inevitably leads to severe complications developing over the years.
Patients after the Fontan operation are also characterized by a significant reduction in exercise capacity, which is observed both in clinical practice in reference centres dealing with patients with congenital heart defects, and in multi-centre studies. Among other things, it was shown that children after the Fontan operation obtained 30% lower values of peak oxygen uptake in the ergospirometric test compared to the control group of healthy children (Amadero P et al., Heart 2018).
The reduced exercise capacity of patients and the development of Fontan circulatory complications affect both the quality of life and the prognosis of adult patients with univentricular heart.
The use of sildenafil in patients with univentricular heart after Fontan operation - a pilot SINFON-POL study.
EU CTIS ID: 2023-503913-31-01
What this study is testing
The main objective of the study is to determine whether, in adult patients with univentricular heart after Fontan operation, in stable clinical condition, without indication for cardiac catheterization, the addition of sildenafil to their existing therapy will result in improved physical performance.
Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
Functionally univentricular heart
Post-Fontan operation condition with the creation of a total cavo-pulmonary connection (TCPC) either extracardiac [extracardiac conduit] or intracardiac [lateral intra-atrial tunnel]
No clinical indications for cardiac catheterization
Age > 18 years
Informed consent to participate in the study
You likely can't join if
Patients with a functionally univentricular heart within 6 months of their last cardiac operation or intravascular procedure
Patients with concomitant diagnoses of: a) cardiovascular events within the last 3 months (acute coronary syndrome, sudden cardiac arrest, ventricular arrhythmias, intracranial hemorrhage, stroke), b) pulmonary embolism, c) infections, d) active bleeding complications, e) severe liver failure (Child-Pugh class C), f) active gastric and/or duodenal peptic ulcer disease, g) malignancy, h) primary muscle and nervous system disease, i) systemic connective tissue disease, j) myocarditis and/or pericarditis, k) predisposition to priapism, sclerosis of the corpus cavernosum or Peyronie's disease, l) sickle cell anemia, leukemia, or multiple myeloma, m) loss of vision in one eye due to non-arteritic anterior ischemic optic neuropathy (NAION), n) enteropathy with protein loss
Pregnancy (positive pregnancy test result), planning pregnancy, breastfeeding
Non-use of contraception during the study - applies to women of reproductive age
Severe central nervous system damage
Taking products containing nitric oxide or nitrates in any form (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, amyl nitrate, pentaerythritol tetranitrate); use in combination with the most potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir)
See the full eligibility criteria
Who can join
Functionally univentricular heart
Post-Fontan operation condition with the creation of a total cavo-pulmonary connection (TCPC) either extracardiac [extracardiac conduit] or intracardiac [lateral intra-atrial tunnel]
No clinical indications for cardiac catheterization
Age > 18 years
Informed consent to participate in the study
What rules you out
Patients with a functionally univentricular heart within 6 months of their last cardiac operation or intravascular procedure
Patients with concomitant diagnoses of: a) cardiovascular events within the last 3 months (acute coronary syndrome, sudden cardiac arrest, ventricular arrhythmias, intracranial hemorrhage, stroke), b) pulmonary embolism, c) infections, d) active bleeding complications, e) severe liver failure (Child-Pugh class C), f) active gastric and/or duodenal peptic ulcer disease, g) malignancy, h) primary muscle and nervous system disease, i) systemic connective tissue disease, j) myocarditis and/or pericarditis, k) predisposition to priapism, sclerosis of the corpus cavernosum or Peyronie's disease, l) sickle cell anemia, leukemia, or multiple myeloma, m) loss of vision in one eye due to non-arteritic anterior ischemic optic neuropathy (NAION), n) enteropathy with protein loss
Pregnancy (positive pregnancy test result), planning pregnancy, breastfeeding
Non-use of contraception during the study - applies to women of reproductive age
Severe central nervous system damage
Taking products containing nitric oxide or nitrates in any form (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, amyl nitrate, pentaerythritol tetranitrate); use in combination with the most potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir)
Patients who were taking pulmonary arterial dilators (sildenafil, tadalafil, riociguat, bosentan, macitentan, ambrisentan, epoprostenol, iloprost, selixipag) in the 6 month period preceding study entry, regardless of the duration of therapy and route of administration (oral, intravenous, subcutaneous, inhalated)
Patients unable to undergo egrospirometric examination
Advanced heart failure (NYHA IV)
Resting arterial oxygen saturation <85%
Chronic kidney disease (creatinine > 150 µmol/l)
Liver damage manifested by a twofold increase in transaminases above the norm
Uncontrolled hypotension (blood pressure < 90/50 mmHg) or risk of hypotension (dehydration, systemic ventricular outflow tract obstruction, autonomic nervous system dysfunction, patients taking alpha-blockers)
Atrial arrhythmia preventing the execution/interpretation of the above-mentioned tests or a life-threatening exercise-induced arrhythmia history
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
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Is it free to join, and do I need insurance?
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How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
BridgeMD is an information and trial-matching tool - not medical advice, and not the
study sponsor. Details come from EU CTIS; the study team decides eligibility.
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