<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01696240</url>
  </required_header>
  <id_info>
    <org_study_id>H-1202-005-396</org_study_id>
    <nct_id>NCT01696240</nct_id>
  </id_info>
  <brief_title>A Randomized Trial of Udenafil Therapy in Patients With Mild Pulmonary Hypertension [ULTIMATE-Mild PHT]</brief_title>
  <official_title>Udenafil Therapy to Improve Symptomatology, Exercise Tolerance and Hemodynamics in Patients With Mild Pulmonary Hypertension [ULTIMATE-Mild PHT]</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dong-A Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seoul National University Bundang Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Seoul National University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesized that udenafil, a newly developed phosphodiesterase type 5&#xD;
      inhibitor, would improve symptom, exercise capacity and hemodynamic status in patients with&#xD;
      mild pulmonary hypertension.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pulmonary arterial hypertension is a devastating progressive disease increasingly&#xD;
      debilitating symptoms. In the past few years, treatment of pulmonary hypertension has&#xD;
      undergone an extraordinary evolution. A selective PDE-5 inhibitor, Sildenafil, has been shown&#xD;
      to be as an effective pulmonary vasodilator as inhaled NO in patients with primary pulmonary&#xD;
      hypertension and has recently been shown to improve exercise capacity, resting hemodynamics,&#xD;
      and WHO functional class in patients with pulmonary hypertension. However, to date, the&#xD;
      effect of Sildenafil have been mainly studied in patients with advanced disease.&#xD;
&#xD;
      Udenafil (Zydena), a newly developed PDE-5 inhibitor, has been proved to have similar&#xD;
      efficacy and safety profile, compared with other PDE-5 inhibitors. However, to date, the&#xD;
      effect of Udenafil in mild pulmonary HT has never been evaluated. Therefore, we hypothesized&#xD;
      that Udenafil, a newly developed phosphodiesterase type 5 inhibitor, would improve symptom,&#xD;
      exercise capacity and hemodynamic status in patients with mild pulmonary hypertension.&#xD;
&#xD;
      In this 12-week, randomized, double-blind, placebo-controlled trial, patients with mild&#xD;
      pulmonary hypertension will be enrolled according to the eligibility criteria. After&#xD;
      randomization, study participants will be assigned to receive either 50mg of Udenafil or&#xD;
      placebo two times a day for 4 weeks, and then the dosage will be doubled to 100mg two times a&#xD;
      day for next 8 weeks. Participants will attend study visits at baseline and weeks 4 and 12.&#xD;
      Physical examination, medical history review, blood sample collection and electrocardiogram&#xD;
      will be conducted on each study visits. At baseline and week 12, participants will undergo&#xD;
      cardiopulmonary exercise test and exercise echocardiography. At every study visits,&#xD;
      researchers will collect health information.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2012</start_date>
  <completion_date type="Anticipated">December 2013</completion_date>
  <primary_completion_date type="Anticipated">December 2013</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of maximal VO2 in cardiopulmonary exercise test</measure>
    <time_frame>Baseline and 12th weeks</time_frame>
    <description>Comparison between groups and within groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of symptomatic status expressed as New York Heart Association (NYHA) functional class</measure>
    <time_frame>Baseline, 4th week, and 12th week</time_frame>
    <description>Comparison between groups and within groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of pulmonary artery systolic pressure (PASP) in echocardiography at rest and during exercise</measure>
    <time_frame>Baseline and 12th week</time_frame>
    <description>Comparison between groups and within groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of left ventricular systolic function expressed as ejection fraction (EF), fractional shortening (FS) in echocardiography</measure>
    <time_frame>Baseline and 12th week</time_frame>
    <description>Comparison between groups and within groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of ventilator efficiency (VE/VCO2 slope) in cardiopulmonary exercise test</measure>
    <time_frame>Baseline and 12th week</time_frame>
    <description>Comparison between groups and within groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of plasma concentration of BNP</measure>
    <time_frame>Baseline, 4th week, and 12th week</time_frame>
    <description>Comparison between groups and within groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause death</measure>
    <time_frame>12th week</time_frame>
    <description>The occurrence of all-cause mortality during 12 week follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac death</measure>
    <time_frame>12th week</time_frame>
    <description>The occurrence of cardiac death including sudden cardiac death during 12 week follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Admission for heart failure</measure>
    <time_frame>12th week</time_frame>
    <description>Admission due to congestive heart failure during 12 week follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite clinical endpoints</measure>
    <time_frame>12th week</time_frame>
    <description>Composite clinical endpoints during 12 week follow-up, are defined as follows:&#xD;
Composite of all-cause death and admission for heart failure Composite of cardiac death and admission for heart failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety endpoint</measure>
    <time_frame>12th week</time_frame>
    <description>Safety endpoint during 12 week follow-up, is defined as follows:&#xD;
Development of facial flushing, febrile sensation, eyeball pain, visual disturbance, headache, penile erection.&#xD;
Intolerance or development of other adverse drug reactions related with study drug.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Mild Pulmonary Hypertension</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Udenafil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>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.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>The same placebo drug of NCT01553721.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Udenafil (Zydena)</intervention_name>
    <description>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.</description>
    <arm_group_label>Udenafil</arm_group_label>
    <other_name>DA-8159 (CAS No 268203-93-6)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Mild pulmonary hypertension defined as estimated pulmonary arterial systolic pressure of&#xD;
        30-50 mmHg (TR jet velocity of 2.5-3.4 m/sec) with current New York Heart association&#xD;
        (NYHA) class II-IV symptoms, left ventricular ejection fraction (LVEF) greater than or&#xD;
        equal to 50% at the time of study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hospitalization for decompensated heart failure or acute treatment with intravenous&#xD;
             loop diuretics or hemofiltration in the 12 months before study entry&#xD;
&#xD;
          -  E/E' ratio greater than or equal to 15 measured by echocardiography&#xD;
&#xD;
          -  E/E' ratio greater than or equal to 8, and left atrial volume index (LAVI) greater&#xD;
             than or equal to 40 ml/m2 measured by echocardiography&#xD;
&#xD;
          -  E/E' ratio greater than or equal to 8 measured by echocardiography, and plasma BNP&#xD;
             concentration greater or equal to 200 pg/ml&#xD;
&#xD;
          -  Significant obstructive or restrictive lung disease&#xD;
&#xD;
          -  Valve disease (greater than mild stenosis or regurgitation)&#xD;
&#xD;
          -  Hypertrophic cardiomyopathy&#xD;
&#xD;
          -  Infiltrative or inflammatory myocardial disease&#xD;
&#xD;
          -  Pericardial disease&#xD;
&#xD;
          -  Primary pulmonary arteriopathy&#xD;
&#xD;
          -  Has neuromuscular, orthopedic, or other non-cardiac condition that prevents individual&#xD;
             from exercise testing&#xD;
&#xD;
          -  Has experienced myocardial infarction or unstable angina, or has undergone&#xD;
             percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)&#xD;
             within 60 days before study entry&#xD;
&#xD;
          -  Non-cardiac illness with estimated life expectancy less than 1 year at the time of&#xD;
             study entry, based on the judgment of the physician&#xD;
&#xD;
          -  Current use of nitrate therapy&#xD;
&#xD;
          -  Current use of other phosphodiesterase 5 inhibitors (ie. sildenafil, vardenafil,&#xD;
             tadalafil) for treatment of impotence or pulmonary artery hypertension&#xD;
&#xD;
          -  Current use of cytochrome P450 3A4 inhibitors (ie. ketoconazole, itraconazole,&#xD;
             erythromycin, saquinavir, cimetidine, protease inhibitors for HIV)&#xD;
&#xD;
          -  Severe hypotension (systolic blood pressure [SBP] less than 90mmHg or diastolic blood&#xD;
             pressure [DBP] less than 50mmHg) or uncontrolled hypertension (SBP greater than&#xD;
             180mmHg or DBP greater than 100mmHg)&#xD;
&#xD;
          -  Known severe renal dysfunction (estimated glomerular filtration rate [GFR] less than&#xD;
             30ml/min/1.73m2 by modified modification of diet in renal disease [MDRD] equation)&#xD;
&#xD;
          -  Known severe liver disease (alanine transaminase [ALT] or aspartate aminotransferase&#xD;
             [AST] level greater than three times the upper normal limit, alkaline phosphatase&#xD;
             [ALP] or total bilirubin greater than two times the upper normal limit)&#xD;
&#xD;
          -  History of leukemia, multiple myeloma or penile deformities that increase the risk for&#xD;
             priapism (eg. Peyronie's disease)&#xD;
&#xD;
          -  History of proliferative diabetic retinopathy, retinitis pigmentosa, nonischemic optic&#xD;
             neuropathy, or unexplained visual disturbance&#xD;
&#xD;
          -  Female patients currently pregnant or women of childbearing age who were not using&#xD;
             contraception&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yong-Jin Kim, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Goo-Yeong Cho, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hyung-Kwan Kim, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Seung-Pyo Lee, MD</last_name>
    <role>Study Director</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yeonyee Yoon, MD</last_name>
    <role>Study Director</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kyung-Hee Kim, MD</last_name>
    <role>Study Director</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>In-Chang Hwang, MD</last_name>
    <role>Study Director</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yong-Jin Kim, MD, PhD</last_name>
    <phone>82-10-3782-9382</phone>
    <email>kimdamas@snu.ac.kr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yeonyee E Yoon, MD</last_name>
    <email>islandtea@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yong-Jin Kim, MD, PhD</last_name>
      <phone>82-10-3782-9382</phone>
      <email>kimdamas@snu.ac.kr</email>
    </contact>
    <contact_backup>
      <last_name>Yeonyee Yoon, MD</last_name>
      <email>islandtea@gmail.com</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yong-Jin Kim, MD, PhD</last_name>
      <phone>82-10-3782-9382</phone>
      <email>kimdamas@snu.ac.kr</email>
    </contact>
    <contact_backup>
      <last_name>Yeonyee E Yoon, MD</last_name>
      <phone>82-31-787-7072</phone>
      <email>islandtea@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009 Apr 28;53(17):1573-619. doi: 10.1016/j.jacc.2009.01.004. No abstract available.</citation>
    <PMID>19389575</PMID>
  </reference>
  <reference>
    <citation>National Pulmonary Hypertension Centres of the UK and Ireland. Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Heart. 2008 Mar;94 Suppl 1:i1-41. doi: 10.1136/hrt.2007.132118. No abstract available.</citation>
    <PMID>18276826</PMID>
  </reference>
  <reference>
    <citation>Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G; ESC Committee for Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009 Oct;30(20):2493-537. doi: 10.1093/eurheartj/ehp297. Epub 2009 Aug 27. No abstract available. Erratum In: Eur Heart J. 2011 Apr;32(8):926.</citation>
    <PMID>19713419</PMID>
  </reference>
  <reference>
    <citation>Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM. Use of sildenafil (Viagra) in patients with cardiovascular disease. Technology and Practice Executive Committee. Circulation. 1999 Jan 5-12;99(1):168-77. doi: 10.1161/01.cir.99.1.168. No abstract available. Erratum In: Circulation 1999 Dec 7;100(23):2389.</citation>
    <PMID>9884398</PMID>
  </reference>
  <reference>
    <citation>Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G; Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005 Nov 17;353(20):2148-57. doi: 10.1056/NEJMoa050010. Erratum In: N Engl J Med. 2006 Jun 1;354(22):2400-1.</citation>
    <PMID>16291984</PMID>
  </reference>
  <reference>
    <citation>Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, Tawakol A, Gerszten RE, Systrom DM, Bloch KD, Semigran MJ. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation. 2007 Oct 2;116(14):1555-62. doi: 10.1161/CIRCULATIONAHA.107.716373. Epub 2007 Sep 4.</citation>
    <PMID>17785618</PMID>
  </reference>
  <reference>
    <citation>Kim BH, Lim HS, Chung JY, Kim JR, Lim KS, Sohn DR, Cho JY, Yu KS, Shin SG, Paick JS, Jang IJ. Safety, tolerability and pharmacokinetics of udenafil, a novel PDE-5 inhibitor, in healthy young Korean subjects. Br J Clin Pharmacol. 2008 Jun;65(6):848-54. doi: 10.1111/j.1365-2125.2008.03107.x. Epub 2008 Mar 3.</citation>
    <PMID>18318773</PMID>
  </reference>
  <reference>
    <citation>Kang KK, Ahn GJ, Sohn YS, Ahn BO, Kim WB. DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right ventricular hypertrophy in a rat model of pulmonary hypertension. J Int Med Res. 2003 Nov-Dec;31(6):517-28. doi: 10.1177/147323000303100608.</citation>
    <PMID>14708417</PMID>
  </reference>
  <verification_date>February 2013</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <last_update_submitted>February 22, 2013</last_update_submitted>
  <last_update_submitted_qc>February 22, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 25, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seoul National University Hospital</investigator_affiliation>
    <investigator_full_name>Yong-Jin Kim</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Pulmonary Hypertension</keyword>
  <keyword>Exercise Capacity</keyword>
  <keyword>Cardiopulmonary Exercise Test</keyword>
  <keyword>Udenafil (Zydena)</keyword>
  <keyword>Phosphodiesterase Type 5 Inhibitors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Udenafil</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01696240
org study id: H-1202-005-396
nct id: NCT01696240
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change of maximal VO2 in cardiopulmonary exercise test
time frame: Baseline and 12th weeks
description: Comparison between groups and within groups.
measure: Change of symptomatic status expressed as New York Heart Association (NYHA) functional class
time frame: Baseline, 4th week, and 12th week
description: Comparison between groups and within groups.
measure: Change of pulmonary artery systolic pressure (PASP) in echocardiography at rest and during exercise
time frame: Baseline and 12th week
description: Comparison between groups and within groups.
measure: Change of left ventricular systolic function expressed as ejection fraction (EF), fractional shortening (FS) in echocardiography
time frame: Baseline and 12th week
description: Comparison between groups and within groups.
measure: Change of ventilator efficiency (VE/VCO2 slope) in cardiopulmonary exercise test
time frame: Baseline and 12th week
description: Comparison between groups and within groups.
measure: Change of plasma concentration of BNP
time frame: Baseline, 4th week, and 12th week
description: Comparison between groups and within groups.
measure: All-cause death
time frame: 12th week
description: The occurrence of all-cause mortality during 12 week follow-up
measure: Cardiac death
time frame: 12th week
description: The occurrence of cardiac death including sudden cardiac death during 12 week follow-up
measure: Admission for heart failure
time frame: 12th week
description: Admission due to congestive heart failure during 12 week follow-up
measure: Composite clinical endpoints
time frame: 12th week
description: 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
measure: Safety endpoint
time frame: 12th week
description: 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: 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.
arm group label: Udenafil
arm group type: Active Comparator
description: 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 type: Drug
intervention name: Placebo
description: 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.
arm group label: Placebo
other name: The same placebo drug of NCT01553721.
intervention type: Drug
intervention name: Udenafil (Zydena)
description: 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.
arm group label: Udenafil
other name: DA-8159 (CAS No 268203-93-6)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yong-Jin Kim, MD, PhD
role: Study Chair
affiliation: Seoul National University Hospital
last name: Goo-Yeong Cho, MD, PhD
role: Principal Investigator
affiliation: Seoul National University Hospital
last name: Hyung-Kwan Kim, MD, PhD
role: Study Director
affiliation: Seoul National University Hospital
last name: Seung-Pyo Lee, MD
role: Study Director
affiliation: Seoul National University Hospital
last name: Yeonyee Yoon, MD
role: Study Director
affiliation: Seoul National University Hospital
last name: Kyung-Hee Kim, MD
role: Study Director
affiliation: Seoul National University Hospital
last name: In-Chang Hwang, MD
role: Study Director
affiliation: Seoul National University Hospital
last name: Yong-Jin Kim, MD, PhD
phone: 82-10-3782-9382
email: kimdamas@snu.ac.kr
last name: Yeonyee E Yoon, MD
email: islandtea@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Korea, Republic of
citation: McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009 Apr 28;53(17):1573-619. doi: 10.1016/j.jacc.2009.01.004. No abstract available.
PMID: 19389575
citation: National Pulmonary Hypertension Centres of the UK and Ireland. Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Heart. 2008 Mar;94 Suppl 1:i1-41. doi: 10.1136/hrt.2007.132118. No abstract available.
PMID: 18276826
citation: Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G; ESC Committee for Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009 Oct;30(20):2493-537. doi: 10.1093/eurheartj/ehp297. Epub 2009 Aug 27. No abstract available. Erratum In: Eur Heart J. 2011 Apr;32(8):926.
PMID: 19713419
citation: Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM. Use of sildenafil (Viagra) in patients with cardiovascular disease. Technology and Practice Executive Committee. Circulation. 1999 Jan 5-12;99(1):168-77. doi: 10.1161/01.cir.99.1.168. No abstract available. Erratum In: Circulation 1999 Dec 7;100(23):2389.
PMID: 9884398
citation: Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G; Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005 Nov 17;353(20):2148-57. doi: 10.1056/NEJMoa050010. Erratum In: N Engl J Med. 2006 Jun 1;354(22):2400-1.
PMID: 16291984
citation: Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, Tawakol A, Gerszten RE, Systrom DM, Bloch KD, Semigran MJ. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation. 2007 Oct 2;116(14):1555-62. doi: 10.1161/CIRCULATIONAHA.107.716373. Epub 2007 Sep 4.
PMID: 17785618
citation: Kim BH, Lim HS, Chung JY, Kim JR, Lim KS, Sohn DR, Cho JY, Yu KS, Shin SG, Paick JS, Jang IJ. Safety, tolerability and pharmacokinetics of udenafil, a novel PDE-5 inhibitor, in healthy young Korean subjects. Br J Clin Pharmacol. 2008 Jun;65(6):848-54. doi: 10.1111/j.1365-2125.2008.03107.x. Epub 2008 Mar 3.
PMID: 18318773
citation: Kang KK, Ahn GJ, Sohn YS, Ahn BO, Kim WB. DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right ventricular hypertrophy in a rat model of pulmonary hypertension. J Int Med Res. 2003 Nov-Dec;31(6):517-28. doi: 10.1177/147323000303100608.
PMID: 14708417
responsible party type: Principal Investigator
investigator affiliation: Seoul National University Hospital
investigator full name: Yong-Jin Kim
investigator title: Associate Professor
mesh term: Hypertension, Pulmonary
mesh term: Hypertension
mesh term: Udenafil