Udenafil Therapy to Improve Symptomatology, Exercise Tolerance and Hemodynamics in Patients With Chronic Systolic Heart Failure (ULTIMATE-SHF)

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

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

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.

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.

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.

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

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.

VO2 max was defined as cardiopulmonary exercise capacity Comparison between groups and within groups

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.

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)

Kim KH, Kim HK, Hwang IC, Lee SP, Cho HJ, Kang HJ, Kim YJ, Sohn DW. ULTIMATE-SHF trial (UdenafiL Therapy to Improve symptoMAtology, exercise Tolerance and hEmodynamics in patients with chronic systolic heart failure): study protocol for a randomized, placebo-controlled, double-blind trial. Trials. 2013 Jun 22;14:188. doi: 10.1186/1745-6215-14-188.