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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

September 26, 2012
February 22, 2013
September 2012
December 2013   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01696240 on ClinicalTrials.gov Archive Site
  • 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.

Same as current
Not Provided
Not Provided
 
A Randomized Trial of Udenafil Therapy in Patients With Mild Pulmonary Hypertension [ULTIMATE-Mild PHT]
Udenafil Therapy to Improve Symptomatology, Exercise Tolerance and Hemodynamics in Patients With Mild Pulmonary Hypertension [ULTIMATE-Mild PHT]

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Mild Pulmonary Hypertension
  • 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.
  • 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)
  • 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.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: Udenafil (Zydena)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
December 2013
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Yong-Jin Kim, MD, PhD 82-10-3782-9382 kimdamas@snu.ac.kr
Contact: Yeonyee E Yoon, MD islandtea@gmail.com
Korea, Republic of
 
NCT01696240
H-1202-005-396
Yes
Yong-Jin Kim, Seoul National University Hospital
Seoul National University Hospital
  • Dong-A ST Co., Ltd.
  • Seoul National University Bundang Hospital
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
Seoul National University Hospital
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP