What side effects are associated with this type of intervention?

Common treatments for Single Ventricle Heart Disease, particularly those involving PDE5 inhibitors like Udenafil, can have several side effects. PDE5 inhibitors are generally well-tolerated but can cause headaches, flushing, dyspepsia, nasal congestion, and visual disturbances. Other treatments for Single Ventricle Heart Disease, such as surgical interventions (e.g., the Fontan procedure), may lead to complications like arrhythmias, protein-losing enteropathy, and liver dysfunction. It's important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved sildenafil, a PDE5 inhibitor, for the treatment of pulmonary arterial hypertension (PAH) in children, which can be relevant for patients with Single Ventricle Heart Disease due to its effects on pulmonary vascular hemodynamics. Sildenafil has been studied in pediatric patients with PAH and has shown improvements in exercise capacity and pulmonary vascular hemodynamics. Udenafil, another PDE5 inhibitor, is currently being evaluated for its efficacy and safety in adolescents who have undergone the Fontan procedure, a common surgery for Single Ventricle Heart Disease.

What other types of research exist?

Promising alternatives to Udenafil for Single Ventricle Heart Disease patients include Sildenafil and Tadalafil, both of which are PDE5 inhibitors with established efficacy in cardiovascular conditions. Emerging treatments such as BI 1015550, a PDE4B inhibitor, and recombinant human pentraxin 2 (rhPTX-2) are also being investigated for their potential benefits in related cardiovascular and pulmonary conditions.

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Udenafil for Single Ventricle Heart Disease (FUEL-2 Trial)

Q: What is the mechanism of action of this treatment?

The most common treatments for Single Ventricle Heart Disease (SVHD) aim to improve cardiac output, reduce pulmonary vascular resistance, and enhance exercise capacity. PDE5 inhibitors, such as Udenafil, work by blocking the enzyme phosphodiesterase type 5 (PDE5), which leads to increased levels of cyclic guanosine monophosphate (cGMP). Elevated cGMP causes relaxation of smooth muscle cells in the pulmonary vasculature, resulting in vasodilation and reduced pulmonary artery pressure. This mechanism is crucial for SVHD patients as it helps to decrease the workload on the single functional ventricle, improve blood flow, and enhance overall cardiovascular efficiency, thereby improving exercise tolerance and quality of life.

Phase 3

Recruiting

Research Sponsored by Mezzion Pharma Co. Ltd

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Males and females with Fontan physiology who are 12 to less than 19 years of age at enrollment

Current antiplatelet or anticoagulant therapy

Must not have

Height < 132 cm

Hospitalization for acute decompensated heart failure within the last 12 months

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to 26 weeks

Awards & highlights

Pivotal Trial

Summary

This trial tests udenafil, a medication that improves blood flow, on adolescents who have had heart surgery (Fontan procedure). It works by relaxing blood vessels to help them exercise better.

Who is the study for?

Adolescents aged 12-18 with Fontan physiology, fluent in the study country's primary language, on antiplatelet or anticoagulant therapy can join. Excluded are those under 132 cm tall, pregnant females or not using contraception, recent heart failure hospitalization, severe ventricular dysfunction, and certain medication users.

What is being tested?

The trial is testing Udenafil against a placebo to see if it's safe and effective for teens who've had the Fontan procedure. Participants will be randomly assigned to either receive Udenafil or a placebo for comparison.

What are the potential side effects?

Udenafil may cause side effects similar to other PDE5 inhibitors like headaches, flushing of the face, nasal congestion, heartburn and potentially serious reactions affecting cardiovascular function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am between 12 and 18 years old with Fontan physiology.

Select...

I am currently on blood thinner medication.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am shorter than 132 cm.

Select...

I was hospitalized for worsening heart failure in the last year.

Select...

I am currently on IV drugs to strengthen my heart muscle.

Select...

I am being evaluated for or listed for a heart transplant.

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I have a heart condition with a specific obstruction causing a pressure difference of more than 4 mmHg.

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Over 80% of my lung function is in one lung.

Select...

My oxygen use during exercise is very low or very high for my age and gender.

Select...

I do not have severe kidney, liver, or digestive problems that could affect how my body handles medication.

Select...

I have not used PDE-5 inhibitors in the last 12 months.

Select...

I am currently taking alpha-blockers or nitrates.

Select...

I am not receiving heart care that would interfere with this study.

Select...

I have been vaccinated for COVID-19 or had symptoms within the last week.

Select...

I am not on blood thinners.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to 26 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to 26 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to 26 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Exercise Capacity

Secondary study objectives

Change in Enhanced Liver Fibrosis (ELF) Score

Change in VO2 at the ventilatory anaerobic threshold (VAT)

Change in ventilatory efficiency (VE/VCO2) at ventilatory anaerobic threshold

+1 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Group I: PlaceboExperimental Treatment1 Intervention

Approximately 218 subjects dosed with matching placebo will be enrolled at approximately 30 sites.

Group II: DrugExperimental Treatment1 Intervention

Approximately 218 subjects dosed with udenafil will be enrolled at approximately 30 sites.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Udenafil

2016

Completed Phase 4

~2380

Placebo

1995

Completed Phase 3

~2670

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Single Ventricle Heart Disease (SVHD) aim to improve cardiac output, reduce pulmonary vascular resistance, and enhance exercise capacity. PDE5 inhibitors, such as Udenafil, work by blocking the enzyme phosphodiesterase type 5 (PDE5), which leads to increased levels of cyclic guanosine monophosphate (cGMP). Elevated cGMP causes relaxation of smooth muscle cells in the pulmonary vasculature, resulting in vasodilation and reduced pulmonary artery pressure. This mechanism is crucial for SVHD patients as it helps to decrease the workload on the single functional ventricle, improve blood flow, and enhance overall cardiovascular efficiency, thereby improving exercise tolerance and quality of life.

Medical treatment of pulmonary hypertension in adults with congenital heart disease: updated and extended results from the International COMPERA-CHD Registry.