Tadalafil for Fontan Physiology
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Mayo Clinic
Must not be taking: Alpha-blockers, Pulmonary vasodilators, Nitrates
Disqualifiers: Under 18, Pregnancy, others
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to find out more about the effectiveness of Tadalafil in improving hemodynamic capabilities, endothelial function, and end-organ function in patients who have previously undergone a Fontan Palliation.
Will I have to stop taking my current medications?
If you are currently using intravenous inotropic drugs, alpha-blockers, pulmonary vasodilators, or nitrates, you will need to stop taking them to participate in this trial.
What data supports the effectiveness of the drug Tadalafil for Fontan Physiology?
Research shows that Tadalafil significantly improves heart function, exercise performance, and quality of life in patients who have undergone the Fontan procedure, which is a heart surgery for certain congenital heart defects.
12345Is tadalafil safe for humans?
Tadalafil is generally safe for humans, with most side effects being mild or moderate and often disappearing without stopping the medication. It does not increase the risk of heart problems and can be safely used with blood pressure medications.
13678How does the drug Tadalafil differ from other treatments for Fontan physiology?
Tadalafil is unique in its use for Fontan physiology as it specifically targets myocardial and endothelial function, improving heart function and exercise performance, which is not the primary focus of other treatments like Sildenafil that mainly reduce pulmonary artery pressure and increase oxygen saturation.
135910Eligibility Criteria
Adults over 18 who've had a Fontan Palliation, can exercise on a supine bike, and are able to have an MRI. They must be willing to give written consent and be scheduled for cardiac catheterization. It's not for those under 18, pregnant or breastfeeding women, people on certain heart medications, or unable to exercise.Inclusion Criteria
I have had a Fontan procedure for my heart condition.
I am scheduled for a heart catheterization procedure.
I am 18 years old or older.
Exclusion Criteria
I am not on any IV drugs to strengthen my heart muscle.
I am under 18 years old.
I am not currently taking alpha-blockers, pulmonary vasodilators, or nitrates.
Participant Groups
The trial is testing if Tadalafil can improve blood flow (hemodynamics), the health of blood vessels (endothelial function), and organ function in patients with Fontan Physiology compared to a placebo (a substance with no active drug).
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Tadalafil GroupExperimental Treatment1 Intervention
Study participants will receive 10 mg of Tadalafil daily for 1 week, then 20 mg daily for 1 week, and finally 40 mg daily for 50 weeks for a total therapy time of 52 weeks. Tadalafil will be taken orally in capsule form once daily.
Group II: Placebo GroupPlacebo Group1 Intervention
Study participants will receive a placebo capsule that looks identical to the Tadalafil capsule. The placebo will be taken orally once daily for 52 weeks.
Tadalafil is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Cialis for:
- Erectile dysfunction
- Pulmonary hypertension
🇪🇺 Approved in European Union as Tadalafil for:
- Erectile dysfunction
- Pulmonary hypertension
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Halley DavisonRochester, MN
Mayo ClinicRochester, MN
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Who is running the clinical trial?
Mayo ClinicLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Effect of Tadalafil on Myocardial and Endothelial Function and Exercise Performance After Modified Fontan Operation. [2018]Better postoperative management of patients who have undergone single ventricle (SV) Fontan procedure could potentially reduce long-term complications and improve the quality of life for patients. The present study determined the effect of tadalafil on myocardial and endothelial function and exercise performance after modified Fontan operation. Patients who had undergone SV modified Fontan operation were enrolled in this clinical trial. The demographic characteristics of the patients were recorded. Before administration of tadalafil and after the trial, ventricular function (MPI, EF, FS, E/A, VTI), exercise performance, and endothelial function were evaluated for sonographic and biochemical markers (FMD, IMT, ICAM, VCAM, NO) using echocardiography, exercise testing, vascular ultrasonography, and biochemical measurements, respectively. A single dose of tadalafil of 1 mg/kg was administered daily for 6 weeks, and the functional class of the patients before and after tadalafil was determined. A total of 15 patients completed this clinical trial. Tadalafil was shown to have a significant effect on myocardial function, exercise performance, and improvement in NYHA functional class (p 0.05), which decreased significantly after tadalafil administration (p
First experience with sildenafil after Fontan operation: short-term outcomes. [2015]We conducted a retrospective study to determine the effect of oral sildenafil administrated as monotherapy after Fontan operation in single ventricle physiology.
Sildenafil and ventriculo-arterial coupling in Fontan-palliated patients: a noninvasive echocardiographic assessment. [2021]The fundamental role of pulmonary vascular resistance in the Fontan circulation is obvious. Medications decreasing this resistance may have an impact on the fate of this population. Hence, we assessed noninvasively the effect of oral sildenafil on the ventriculo-arterial coupling in patients with Fontan circulation. In a single-center, prospective case series study, 23 patients with fenestrated extracardiac total cavopulmonary connection age 12-31 years were enrolled in this study. Clinical characteristics and echocardiographic examination were performed before and after a 1 week course of sildenafil at 0.5 mg/kg every 8 h. Sildenafil had no effect on heart rate and blood pressure. However, oxygen saturation was significantly increased with sildenafil (87.6 ± 4.3 vs. 90.1 ± 3.6; P
Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients. [2015]We sought to assess the effects of sildenafil on exercise capacity and haemodynamic response to exercise in Fontan patients.
Modulation of pulmonary vascular resistance as a target for therapeutic interventions in Fontan patients: focus on phosphodiesterase inhibitors. [2015]Despite advancements in surgical techniques over the past 20 years, Fontan patients have decreased exercise capacity as a consequence of an inherent inability to adequately increase cardiac output during exercise. They are also affected by several complications that are associated with considerable morbidity and mortality. As the systemic and pulmonary circulations are placed in series without a subpulmonary ventricle propelling blood through the pulmonary vasculature, the systemic venous pressure and the respiratory mechanics are the only forces driving pulmonary blood flow. In Fontan circulation, pulmonary vascular resistance is the single most important factor involved in the limitation of cardiac output and treatments able to decrease pulmonary vascular resistance might conversely improve cardiac output and exercise capacity. In this article we discuss the initial experience with the use of sildenafil in Fontan patients and we discuss the possible mechanisms through which sildenafil might positively act in Fontan circulation.
[Safety and tolerance of tadalafil in the treatment of erectile dysfunction]. [2015]The benefit of tadalafil should be justified by its safety and tolerance in the chronic treatment of erectile dysfunction (ED) in general and high-risk population. The main treatment-emergent adverse events, chiefly induced by the interactions of tadalafil with PDE5 and isoforms, are mild or moderate in severity, transient and reversible, which may disappear without drug withdrawal. Tadalafil does not add to the risk and severity of cardiovascular problems, and can be safely co-administered with antihypertensives and selective a-receptor blockers.
Sildenafil exposure and hemodynamic effect after Fontan surgery. [2023]Determine sildenafil exposure and hemodynamic effect in children after Fontan single-ventricle surgery.
Safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension: a sub-group analysis based on Japan post-marketing surveillance. [2018]To evaluate the long-term safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) in real-world clinical practice.
Sildenafil Increases Systemic Saturation and Reduces Pulmonary Artery Pressure in Patients with Failing Fontan Physiology. [2021]OBJECTIVE: The purpose of this study was to investigate the effect of sildenafil in patients with failing Fontan physiology. DESIGN: A retrospective chart review was performed to compare history and available data in patients with Fontan circulations before and after starting sildenafil. The paired and unpaired Student's t-tests were used for statistical analyses. PATIENTS: Six patients at our institution with Fontan physiology, persistent symptoms of cyanosis or effusion, and poor hemodynamics as measured in the catheterization laboratory were placed on sildenafil. One patient was not included in the analysis because of insufficient length of treatment. All patients had symptoms of failing Fontan hemodynamics with either persistent cyanosis or effusions. In this group, the mean pulmonary artery pressure was greater than 15 mm Hg (17.4 ± 1.5 mm Hg) with mean estimated pulmonary vascular resistance of 3.5 ± 1.0 Wood units × m(2) prior to starting sildenafil. RESULTS: Sildenafil significantly increased the systemic arterial oxyhemoglobin saturation in this group (82.8 ± 7.3% pre-treatment vs. 91.0 ± 5.5% post-treatment, P = .017). In the four out of five patients who have had follow-up catheterizations, there was a significant decrease in pulmonary artery pressure (17.4 ± 1.5 mm Hg pre-treatment vs. 13.8 ± 2.1 mm Hg post-treatment, P = .018) and in estimated pulmonary vascular resistance pre- and post-sildenafil treatment (3.5 ± 1.0 Wood units × m(2) pre-treatment vs. 2.0 ± 0.4 Wood units × m(2) post-treatment, P = .031). CONCLUSIONS: Sildenafil may be a useful adjunct to therapy in patients with failing Fontan physiology likely through its function as a pulmonary vasodilator.
Resolution of protein-losing enteropathy and normalization of mesenteric Doppler flow with sildenafil after Fontan. [2015]A 9.5-year-old girl after Fontan procedure for hypoplastic left heart syndrome had recurrent protein-losing enteropathy (PLE) develop 2 months after partial catheter closure of the Fontan fenestration. Despite satisfactory hemodynamic measurements under general anesthesia, we postulated that she suffered from increased pulmonary vascular reactivity and commenced her on Sildenafil treatment. After 6 weeks of oral Sildenafil treatment, her serum albumin and the fecal alpha-1-antitrypsin levels normalized, and her exercise tolerance had increased. There was also an improvement of the mesenteric arterial flow patterns on Doppler studies. Sildenafil should be considered in the treatment of PLE after the Fontan procedure.