A Randomized Trial of Udenafil Therapy in Patients With Mild Pulmonary Hypertension [ULTIMATE-Mild PHT]

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Seoul National University Hospital
Sponsor:
Collaborators:
Dong-A ST Co., Ltd.
Seoul National University Bundang Hospital
Information provided by (Responsible Party):
Yong-Jin Kim, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01696240
First received: September 26, 2012
Last updated: February 22, 2013
Last verified: February 2013
  Purpose

The investigators hypothesized that udenafil, a newly developed phosphodiesterase type 5 inhibitor, would improve symptom, exercise capacity and hemodynamic status in patients with mild pulmonary hypertension.


Condition Intervention Phase
Mild Pulmonary Hypertension
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
Official Title: Udenafil Therapy to Improve Symptomatology, Exercise Tolerance and Hemodynamics in Patients With Mild Pulmonary Hypertension [ULTIMATE-Mild PHT]

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • Change of maximal VO2 in cardiopulmonary exercise test [ Time Frame: Baseline and 12th weeks ] [ Designated as safety issue: No ]
    Comparison between groups and within groups.


Secondary Outcome Measures:
  • 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.

  • Change of left ventricular systolic function expressed as ejection fraction (EF), fractional shortening (FS) in echocardiography [ Time Frame: Baseline 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 plasma concentration of BNP [ Time Frame: Baseline, 4th week, and 12th week ] [ Designated as safety issue: No ]
    Comparison between groups and within groups.

  • All-cause death [ Time Frame: 12th week ] [ Designated as safety issue: No ]
    The occurrence of all-cause mortality during 12 week follow-up

  • Cardiac death [ Time Frame: 12th week ] [ Designated as safety issue: No ]
    The occurrence of cardiac death including sudden cardiac death during 12 week follow-up

  • Admission for heart failure [ Time Frame: 12th week ] [ Designated as safety issue: No ]
    Admission due to congestive heart failure during 12 week follow-up

  • Composite clinical endpoints [ Time Frame: 12th week ] [ Designated as safety issue: No ]

    Composite clinical endpoints during 12 week follow-up, are defined as follows:

    Composite of all-cause death and admission for heart failure Composite of cardiac death and admission for heart failure


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

    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.



Estimated Enrollment: 40
Study Start Date: September 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
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.
Other Name: The same placebo drug of NCT01553721.
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.
Other Names:
  • Udenafil (Zydena)
  • DA-8159 (CAS No 268203-93-6)

Detailed Description:

Pulmonary arterial hypertension is a devastating progressive disease increasingly debilitating symptoms. In the past few years, treatment of pulmonary hypertension has undergone an extraordinary evolution. A selective PDE-5 inhibitor, Sildenafil, has been shown to be as an effective pulmonary vasodilator as inhaled NO in patients with primary pulmonary hypertension and has recently been shown to improve exercise capacity, resting hemodynamics, and WHO functional class in patients with pulmonary hypertension. However, to date, the effect of Sildenafil have been mainly studied in patients with advanced disease.

Udenafil (Zydena), a newly developed PDE-5 inhibitor, has been proved to have similar efficacy and safety profile, compared with other PDE-5 inhibitors. However, to date, the effect of Udenafil in mild pulmonary HT has never been evaluated. Therefore, we hypothesized that Udenafil, a newly developed phosphodiesterase type 5 inhibitor, would improve symptom, exercise capacity and hemodynamic status in patients with mild pulmonary hypertension.

In this 12-week, randomized, double-blind, placebo-controlled trial, patients with mild pulmonary hypertension 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 and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Mild pulmonary hypertension defined as estimated pulmonary arterial systolic pressure of 30-50 mmHg (TR jet velocity of 2.5-3.4 m/sec) with current New York Heart association (NYHA) class II-IV symptoms, left ventricular ejection fraction (LVEF) greater than or equal to 50% at the time of study entry

Exclusion Criteria:

  • Hospitalization for decompensated heart failure or acute treatment with intravenous loop diuretics or hemofiltration in the 12 months before study entry
  • E/E' ratio greater than or equal to 15 measured by echocardiography
  • E/E' ratio greater than or equal to 8, and left atrial volume index (LAVI) greater than or equal to 40 ml/m2 measured by echocardiography
  • E/E' ratio greater than or equal to 8 measured by echocardiography, and plasma BNP concentration greater or equal to 200 pg/ml
  • Significant obstructive or restrictive lung disease
  • Valve disease (greater than mild stenosis or regurgitation)
  • Hypertrophic cardiomyopathy
  • Infiltrative or inflammatory myocardial disease
  • Pericardial disease
  • Primary pulmonary arteriopathy
  • Has neuromuscular, orthopedic, or other non-cardiac condition that prevents individual from exercise testing
  • Has experienced myocardial infarction or unstable angina, or has undergone percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 60 days before study entry
  • Non-cardiac illness with estimated life expectancy less than 1 year at the time of study entry, based on the judgment of the physician
  • Current use of nitrate therapy
  • Current use of other phosphodiesterase 5 inhibitors (ie. sildenafil, vardenafil, tadalafil) for treatment of impotence or pulmonary artery hypertension
  • Current use of cytochrome P450 3A4 inhibitors (ie. ketoconazole, itraconazole, erythromycin, saquinavir, cimetidine, protease inhibitors for HIV)
  • Severe hypotension (systolic blood pressure [SBP] less than 90mmHg or diastolic blood pressure [DBP] less than 50mmHg) or uncontrolled hypertension (SBP greater than 180mmHg or DBP greater than 100mmHg)
  • Known severe renal dysfunction (estimated glomerular filtration rate [GFR] less than 30ml/min/1.73m2 by modified modification of diet in renal disease [MDRD] equation)
  • Known severe liver disease (alanine transaminase [ALT] or aspartate aminotransferase [AST] level greater than three times the upper normal limit, alkaline phosphatase [ALP] or total bilirubin greater than two times the upper normal limit)
  • History of leukemia, multiple myeloma or penile deformities that increase the risk for priapism (eg. Peyronie's disease)
  • History of proliferative diabetic retinopathy, retinitis pigmentosa, nonischemic optic neuropathy, or unexplained visual disturbance
  • Female patients currently pregnant or women of childbearing age who were not using contraception
  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: NCT01696240

Contacts
Contact: Yong-Jin Kim, MD, PhD 82-10-3782-9382 kimdamas@snu.ac.kr
Contact: Yeonyee E Yoon, MD islandtea@gmail.com

Locations
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Yong-Jin Kim, MD, PhD    82-10-3782-9382    kimdamas@snu.ac.kr   
Contact: Yeonyee Yoon, MD       islandtea@gmail.com   
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Yong-Jin Kim, MD, PhD    82-10-3782-9382    kimdamas@snu.ac.kr   
Contact: Yeonyee E Yoon, MD    82-31-787-7072    islandtea@gmail.com   
Sponsors and Collaborators
Seoul National University Hospital
Dong-A ST Co., Ltd.
Seoul National University Bundang Hospital
Investigators
Study Chair: Yong-Jin Kim, MD, PhD Seoul National University Hospital
Principal Investigator: Goo-Yeong Cho, MD, PhD Seoul National University Hospital
Study Director: Hyung-Kwan Kim, MD, PhD Seoul National University Hospital
Study Director: Seung-Pyo Lee, MD Seoul National University Hospital
Study Director: Yeonyee Yoon, MD Seoul National University Hospital
Study Director: Kyung-Hee Kim, MD Seoul National University Hospital
Study Director: In-Chang Hwang, MD Seoul National University Hospital
  More Information

Publications:

Responsible Party: Yong-Jin Kim, Associate Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01696240     History of Changes
Other Study ID Numbers: H-1202-005-396
Study First Received: September 26, 2012
Last Updated: February 22, 2013
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Seoul National University Hospital:
Pulmonary Hypertension
Exercise Capacity
Cardiopulmonary Exercise Test
Udenafil (Zydena)
Phosphodiesterase Type 5 Inhibitors

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Udenafil
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014