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Mild Pulmonary HypertensionPhase 3NCT01696240

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

A Phase 3 study testing Udenafil (Zydena) in people with Mild Pulmonary Hypertension, run by Seoul National University Hospital at 2 sites in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mild Pulmonary Hypertension
What is being tested?
Udenafil (Zydena)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
2 sitesSouth Korea
Study dates
Sep 2012to Dec 2013
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 22Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

Yong-Jin Kim, MD, PhD contact

82-10-3782-9382

kimdamas@snu.ac.kr

Yeonyee E Yoon, MD contact

islandtea@gmail.com

South Korea2 sites, 2 recruiting
  • Seoul National University Hospital

    Seoul, 110-744

    Yong-Jin Kim, MD, PhD, 82-10-3782-9382, kimdamas@snu.ac.kr

    Yeonyee Yoon, MD, islandtea@gmail.com

    Recruiting
  • Seoul National University Hospital

    Seoul, 110-744

    Yong-Jin Kim, MD, PhD, 82-10-3782-9382, kimdamas@snu.ac.kr

    Yeonyee E Yoon, MD, 82-31-787-7072, islandtea@gmail.com

    Recruiting

Other trials in South Korea

About this study

Official title: 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.

Read the 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.

Being tested
Placebo, Udenafil (Zydena)
Keywords
Pulmonary Hypertension, Exercise Capacity, Cardiopulmonary Exercise Test, Udenafil (Zydena), Phosphodiesterase Type 5 Inhibitors
Medical subject headings
Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Also called The same placebo drug of NCT01553721.

    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.

  • Udenafil (Zydena)Drug

    Also called DA-8159 (CAS No 268203-93-6)

    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.

Study groups in NCT01696240
Study groupRoleWhat they receive
PlaceboPlacebo comparatorCapsule 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.
Receives: Drug: Placebo
UdenafilActive comparatorPatients 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.
Receives: Drug: Udenafil (Zydena)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change of maximal VO2 in cardiopulmonary exercise test

    Comparison between groups and within groups.

    Measured: Baseline and 12th weeks

Secondary outcomes (10)
  1. Change of symptomatic status expressed as New York Heart Association (NYHA) functional class

    Comparison between groups and within groups.

    Measured: Baseline, 4th week, and 12th week

  2. Change of pulmonary artery systolic pressure (PASP) in echocardiography at rest and during exercise

    Comparison between groups and within groups.

    Measured: Baseline and 12th week

  3. Change of left ventricular systolic function expressed as ejection fraction (EF), fractional shortening (FS) in echocardiography

    Comparison between groups and within groups.

    Measured: Baseline and 12th week

  4. Change of ventilator efficiency (VE/VCO2 slope) in cardiopulmonary exercise test

    Comparison between groups and within groups.

    Measured: Baseline and 12th week

  5. Change of plasma concentration of BNP

    Comparison between groups and within groups.

    Measured: Baseline, 4th week, and 12th week

  6. All-cause death

    The occurrence of all-cause mortality during 12 week follow-up

    Measured: 12th week

  7. Cardiac death

    The occurrence of cardiac death including sudden cardiac death during 12 week follow-up

    Measured: 12th week

  8. Admission for heart failure

    Admission due to congestive heart failure during 12 week follow-up

    Measured: 12th week

  9. Composite clinical endpoints

    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

    Measured: 12th week

  10. 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.

    Measured: 12th week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionDec 2013 (estimated)
  4. Study completionDec 2013 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01696240
Sponsor's protocol ID
H-1202-005-396
Status last verified
Feb 2013
First submitted
26 Sep 2012
Last updated
25 Feb 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 19389575
  • 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.

    PubMed 18276826
  • 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.

    PubMed 19713419
  • 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.

    PubMed 9884398
  • 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.

    PubMed 16291984
  • 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.

    PubMed 17785618
  • 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.

    PubMed 18318773
  • 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.

    PubMed 14708417

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Udenafil (Zydena) in people with Mild Pulmonary Hypertension, run by Seoul National University Hospital at 2 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 25 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Yong-Jin Kim, MD, PhD (82-10-3782-9382, kimdamas@snu.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of maximal VO2 in cardiopulmonary exercise test (time frame: Baseline and 12th weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01696240, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2013.

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