Udenafil Therapy to Improve Symptomatology, Exercise Tolerance and Hemodynamics in Patients With Chronic Systolic Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to determine if udenafil improves exercise tolerance in patients with systolic heart failure.

Detailed Description
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Udenafil (Zydena), a newly developed PDE-5 inhibitor, has been proved to have similar efficacy and safety profile, compared with other PDE-5 inhibitors. Also, laboratory data showed that udenafil inhibits ventricular hypertrophy and fibrosis in rat heart failure model. Based on these results, the investigators hypothesized that udenafil would improve symptom, exercise capacity and hemodynamic status in patients with systolic heart failure. In this 12-week, randomized, double-blind, placebo-controlled trial, patients with systolic heart failure will be enrolled according to the eligibility criteria. After randomization, study participants will be assigned to receive either 50mg of udenafil or placebo two times a day for 4 weeks, and then the dosage will be doubled to 100mg two times a day for next 8 weeks. Participants will attend study visits at baseline and weeks 4 and 12. Physical examination, medical history review, blood sample collection and electrocardiogram will be conducted on each study visits. At baseline and week 12, participants will undergo cardiopulmonary exercise test and exercise echocardiography. At every study visits,researchers will collect health information.

Conditions
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Systolic Heart Failure

Intervention / Treatment
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* Drug: Placebo
* Drug: Udenafil (Zydena)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age, LV EF < 40% Exclusion Criteria: long-term use of medications that inhibit cytochrome P450 3A4. inability patients with exercise test primary pulmonary artery hypertension severe hypotension (< 90/50mmHg) or severe hypertension (> 170/100mmHg)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo arm<br>Capsule that is identically appearing with udenafil will be administered to patients in placebo group. For the first 4 weeks, patients will receive 50 mg of placebo drug two times a day, and then the dosage will be doubled to 100 mg two times a day for next 8 weeks. | Drug: Placebo<br>* Capsule, appears identical with udenafil, will be provided by Dong-A pharmaceutical company. Patients will receive 50 mg of placebo drug two times a day for 4 weeks, and then the dosage will be escalated to 100 mg two times a day for next 8 weeks<br>|
| Active Comparator: Udenafil<br>Patients will receive 50 mg of udenafil two times a day, and then the dosage will be doubled to 100 mg two times a day for next 8 weeks. | Drug: Udenafil (Zydena)<br>* Udenafil (Zydena), a newly developed PDE-5 inhibitor by Dong-A pharmaceutical company, will be administered to patients in this group, 50 mg two times a day for 4 weeks, and then the dosage will be escalated to 100 mg two times a day for next 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VO2max with cardiopulmonary exercise test | VO2 max was defined as cardiopulmonary exercise capacity Comparison between groups and within groups | Baseline and 12th weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes of left ventricle ejection fraction | comparison between groups and within groups | baseline and 12 th week | 
| serum BNP level | Comparison between groups and within groups | Baseline, 4th week, and 12th week | 
| Change of ventilator efficiency (VE/VCO2 slope) in cardiopulmonary exercise test | Comparison between groups and within groups | Baseline and 12th week | 
| Change of symptomatic status expressed as New York Heart Association (NYHA) functional class | Comparison between groups and within groups | Baseline, 4th week, and 12th week | 
| Change of pulmonary artery systolic pressure (PASP) in echocardiography at rest and during exercise | Comparison between groups and within groups. | Baseline and 12th week | 
| Safety endpoint | Safety endpoint during 12 week follow-up, is defined as follows: Development of facial flushing, febrile sensation, eyeball pain, visual disturbance, headache, penile erection. Intolerance or development of other adverse drug reactions related with study drug. | 12th week | 
| Change of symptomatic status expressed as Borg dyspnea index | Comparison between groups and within groups. | baseline, 4 weeks and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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systolic heart failure, udenafil, exercise capacity