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

NCT01696240 | Unknown Phase 3 DMC

• 1 other identifier: H-1202-005-396
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Mild Pulmonary Hypertension

Keywords

Pulmonary Hypertension; Exercise Capacity; Cardiopulmonary Exercise Test; Udenafil (Zydena); Phosphodiesterase Type 5 Inhibitors

Outcome Measures

Primary Outcomes (1)

• Change of maximal VO2 in cardiopulmonary exercise test

  Comparison between groups and within groups.

  Baseline and 12th weeks

Secondary Outcomes (10)

• Change of symptomatic status expressed as New York Heart Association (NYHA) functional class

  Baseline, 4th week, and 12th week

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

  Baseline and 12th week

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

  Baseline and 12th week

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

  Baseline and 12th week

• Change of plasma concentration of BNP

  Baseline, 4th week, and 12th week

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Udenafil

ACTIVE COMPARATOR

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)

Interventions

Placebo DRUG

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.

Also known as: The same placebo drug of NCT01553721.

Placebo

Udenafil (Zydena) DRUG

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.

Also known as: DA-8159 (CAS No 268203-93-6)

Udenafil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Dong-A Pharmaceutical Co., Ltd.: collaborator
• Seoul National University Bundang Hospital: collaborator

Study Sites (2)

Seoul National University Hospital

Seoul, 110-744, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 110-744, South Korea

RECRUITING

Related Publications (8)

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 19713419 BACKGROUND

• 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.

  PMID: 9884398 BACKGROUND

• 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.

  PMID: 16291984 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

udenafil

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Yong-Jin Kim, MD, PhD

  Seoul National University Hospital

  STUDY CHAIR

• Goo-Yeong Cho, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

• 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

  STUDY DIRECTOR

Central Study Contacts

Yong-Jin Kim, MD, PhD

CONTACT

82-10-3782-9382; kimdamas@snu.ac.kr

Yeonyee E Yoon, MD

CONTACT

islandtea@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 26, 2012
• First Posted: September 28, 2012
• Study Start: September 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: February 25, 2013

Record last verified: 2013-02

Locations

KR (2)