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

This study has been terminated.
(Substantial benefit was observed in the active treatment group)
Sponsor:
Collaborator:
Dong-A Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Hyung-Kwan Kim, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01646515
First received: June 13, 2012
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Systolic Heart Failure
Drug: Placebo
Drug: Udenafil (Zydena)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • VO2max with cardiopulmonary exercise test [ Time Frame: Baseline and 12th weeks ] [ Designated as safety issue: No ]

    VO2 max was defined as cardiopulmonary exercise capacity

    Comparison between groups and within groups



Secondary Outcome Measures:
  • The changes of left ventricle ejection fraction [ Time Frame: baseline and 12 th week ] [ Designated as safety issue: No ]
    comparison between groups and within groups

  • serum BNP level [ Time Frame: Baseline, 4th week, and 12th week ] [ Designated as safety issue: No ]
    Comparison between groups and within groups

  • Change of ventilator efficiency (VE/VCO2 slope) in cardiopulmonary exercise test [ Time Frame: Baseline and 12th week ] [ Designated as safety issue: No ]
    Comparison between groups and within groups

  • Change of symptomatic status expressed as New York Heart Association (NYHA) functional class [ Time Frame: Baseline, 4th week, and 12th week ] [ Designated as safety issue: No ]
    Comparison between groups and within groups

  • Change of pulmonary artery systolic pressure (PASP) in echocardiography at rest and during exercise [ Time Frame: Baseline and 12th week ] [ Designated as safety issue: No ]
    Comparison between groups and within groups.

  • Safety endpoint [ Time Frame: 12th week ] [ Designated as safety issue: Yes ]

    Safety endpoint during 12 week follow-up, is defined as follows:

    1. Development of facial flushing, febrile sensation, eyeball pain, visual disturbance, headache, penile erection.
    2. Intolerance or development of other adverse drug reactions related with study drug.

  • Change of symptomatic status expressed as Borg dyspnea index [ Time Frame: baseline, 4 weeks and 12 weeks ] [ Designated as safety issue: Yes ]
    Comparison between groups and within groups.


Other Outcome Measures:
  • All cause death, cardiac death, and heart failure-related admission and their composite [ Time Frame: 12 week ] [ Designated as safety issue: Yes ]
    All cause death, cardiac death, and heart failure-related admission and their composite


Enrollment: 41
Study Start Date: December 2011
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01646515

Locations
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
Seoul National University Hospital
Dong-A Pharmaceutical Co., Ltd.
  More Information

No publications provided by Seoul National University Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hyung-Kwan Kim, Associate Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01646515     History of Changes
Other Study ID Numbers: H-1102-063-352
Study First Received: June 13, 2012
Last Updated: April 22, 2014
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Seoul National University Hospital:
systolic heart failure
udenafil
exercise capacity

Additional relevant MeSH terms:
Heart Failure
Heart Failure, Systolic
Heart Diseases
Cardiovascular Diseases
Udenafil
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014