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

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

Study Overview

• Status: Terminated
• Conditions: Systolic Heart Failure
• Intervention / Treatment: Drug: Udenafil (Zydena); Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo arm; 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; 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
ACTIVE_COMPARATOR: Udenafil; 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); 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.

What is the study measuring?

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
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
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 symptomatic status expressed as Borg dyspnea index	Comparison between groups and within groups.	baseline, 4 weeks and 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause death, cardiac death, and heart failure-related admission and their composite	All cause death, cardiac death, and heart failure-related admission and their composite	12 week

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Dong-A Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): January 1, 2014
• Study Completion (ACTUAL): January 1, 2014

Study Registration Dates

• First Submitted: June 13, 2012
• First Submitted That Met QC Criteria: July 19, 2012
• First Posted (ESTIMATE): July 20, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): April 24, 2014
• Last Update Submitted That Met QC Criteria: April 22, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: exercise capacity; systolic heart failure; udenafil
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Murmurs; Heart Failure; Systolic Murmurs; Heart Failure, Systolic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Udenafil
• Other Study ID Numbers: H-1102-063-352