Udenafil for Single Ventricle Heart Disease

(FUEL-2 Trial)

Recruiting at 43 trial locations

Overseen By WG Kim

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Mezzion Pharma Co. Ltd

Must be taking: Antiplatelet, Anticoagulant

Must not be taking: PDE-5 inhibitors, Alpha-blockers

Disqualifiers: Heart failure, Liver cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

436 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on antiplatelet or anticoagulant therapy to participate. You cannot use PDE-5 inhibitors, alpha-blockers, or nitrates during the trial.

How does the drug Udenafil differ from other treatments for single ventricle heart disease?

Udenafil is unique because it is a phosphodiesterase type 5 inhibitor, which means it works by relaxing blood vessels and improving blood flow, potentially offering benefits for heart conditions by enhancing circulation. This mechanism is different from other treatments like ramipril or diltiazem, which primarily focus on reducing blood pressure or heart workload. ^{1 2 3 4 5}

Research Team

WG Kim

Principal Investigator

Mezzion Pharma Co. Ltd

Eligibility Criteria

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.

Inclusion Criteria

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

Participant fluency in primary language of country in which study is being conducted

Participant consent or parental/guardian consent and participant assent

Exclusion Criteria

I have been diagnosed with protein losing enteropathy, plastic bronchitis in the last 3 years, or have liver cirrhosis.

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

You cannot finish the exercise test during the initial screening.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive udenafil or placebo for 26 weeks

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Udenafil

Trial Overview 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.

Participant Groups

Group I: Placebo Experimental Treatment 1 Intervention

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

Group II: Drug Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Mezzion Pharma Co. Ltd

Lead Sponsor

Trials

5

Recruited

1,300+

Findings from Research

In a study of 223 patients with moderate chronic congestive heart failure, treatment with the angiotensin converting enzyme inhibitor ramipril resulted in a significant decrease in blood pressure and fewer patients experiencing deterioration in their heart failure classification compared to placebo.

While both groups showed an increase in maximal exercise time, the difference between ramipril and placebo was not statistically significant, suggesting that ramipril's primary benefits may lie in improving heart function and reducing the need for additional heart failure medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of effect on exercise capacity of 12-weeks treatment with ramipril in patients with moderate congestive heart failure. Ramipril Study Group. Gundersen, T., Swedberg, K., Amtorp, O., et al.[2019]

In a study of 20 male patients with a history of myocardial infarction, intravenous diltiazem significantly lowered resting blood pressure and systemic vascular resistance while increasing cardiac index, indicating its efficacy in improving hemodynamic parameters.

During exercise, diltiazem further reduced mean pulmonary arterial pressure and total pulmonary resistance, demonstrating its potential to enhance cardiac performance without significantly increasing cardiac workload.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemodynamic effects of diltiazem at rest and during exercise in patients with previous myocardial infarction. Cobelli, F., Opasich, C., Riccardi, G., et al.[2019]

In a trial involving 227 patients with chronic stable angina, diltiazem hydrochloride in a once-daily capsule formulation showed a significant linear dose response, improving exercise tolerance and delaying exercise termination time, indicating its efficacy in managing angina symptoms.

The study found that doses up to 240 mg/day improved exercise tolerance without increasing the rate of treatment-related adverse effects compared to placebo, suggesting a favorable safety profile for this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response evaluation of once-daily therapy with a new formulation of diltiazem for stable angina pectoris. Diltiazem CD Study Group. Thadani, U., Glasser, S., Bittar, N., et al.[2019]

In a study involving 13 anesthetized dogs, amlodipine did not improve vascular capacitance or reduce cardiac filling pressures in a model of acute ischemic heart failure, suggesting it may not have beneficial hemodynamic effects in this condition.

The results indicated a negative inotropic effect of amlodipine in heart failure, as evidenced by decreased left ventricular stroke work in the heart failure group, leaving the mechanism of its benefits in chronic heart failure unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular and cardiac effects of amlodipine in acute heart failure in dogs. Isaac, DL., Belenkie, I., Manyari, DE., et al.[2016]

In a multicenter trial with 345 participants, carvedilol significantly improved left ventricular (LV) function and reduced mortality rates in patients with mild to moderate chronic heart failure, with a 73% lower risk of all-cause mortality compared to placebo.

Carvedilol also decreased hospitalization rates by 58% to 64% and was generally well tolerated, indicating its efficacy and safety as a treatment for chronic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Bristow, MR., Gilbert, EM., Abraham, WT., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Absence of effect on exercise capacity of 12-weeks treatment with ramipril in patients with moderate congestive heart failure. Ramipril Study Group. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Haemodynamic effects of diltiazem at rest and during exercise in patients with previous myocardial infarction. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Dose-response evaluation of once-daily therapy with a new formulation of diltiazem for stable angina pectoris. Diltiazem CD Study Group. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Vascular and cardiac effects of amlodipine in acute heart failure in dogs. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. [2022]