A Randomized Trial of Udenafil Therapy in Patients With Heart Failure With Preserved Ejection Fraction [ULTIMATE-HFpEF]

NCT01599117 | Unknown Phase 3 DMC

• 1 other identifier: H-1202-006-396
• Study Type: interventional
• Target: 52
• 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 heart failure with preserved ejection fraction (HFpEF).

Conditions

Diastolic Heart Failure

Keywords

Heart Failure with Preserved Ejection Fraction; Diastolic Heart Failure; 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 (13)

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

  Baseline and 12th week

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

  Baseline, 4th week, and 12th week

• Change of symptomatic status expressed as Borg dyspnea index

  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

Study Arms (2)

Placebo arm

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 arm

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:

• Previous clinical diagnosis of heart failure with preserved ejection fraction (or diastolic heart failure) with current New York Heart association (NYHA) class II-IV symptoms
• Left ventricular ejection fraction (LVEF) greater than or equal to 50%, as determined by echocardiography in the 12 months before study entry
• Has experienced at least one of the following in the 12 months before study entry
• Hospitalization for decompensated heart failure
• Acute treatment with intravenous loop diuretics or hemofiltration
• 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

You may not qualify if:

• History of reduced LVEF (less than 50%)
• Valve disease (greater than mild stenosis or regurgitation)
• Hypertrophic cardiomyopathy
• Infiltrative or inflammatory myocardial disease
• Pericardial disease
• Obstructive or restrictive lung 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)
• Resting heart rate (HR) greater than 100bpm

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 Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 110-744, South Korea

RECRUITING

Related Publications (7)

• Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, Gong Y, Liu PP. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med. 2006 Jul 20;355(3):260-9. doi: 10.1056/NEJMoa051530.

  PMID: 16855266 BACKGROUND

• Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007 Oct;28(20):2539-50. doi: 10.1093/eurheartj/ehm037. Epub 2007 Apr 11.

  PMID: 17428822 BACKGROUND

• Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, Kass DA. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005 Feb;11(2):214-22. doi: 10.1038/nm1175. Epub 2005 Jan 23.

  PMID: 15665834 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

• Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail. 2011 Jan;4(1):8-17. doi: 10.1161/CIRCHEARTFAILURE.110.944694. Epub 2010 Oct 29.

  PMID: 21036891 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

Heart Failure, Diastolic

Interventions

udenafil

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases

Study Officials

• Yong-Jin Kim, MD, PhD

  Seoul National University Hospital

  STUDY CHAIR

• In-Chang Hwang, MD

  Seoul National University Hospital

  STUDY DIRECTOR

• Goo-Yeong Cho, MD, PhD

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

• Hyung-Kwan Kim, MD, PhD

  Seoul National University Hospital

  STUDY DIRECTOR

• Seung-Pyo Lee, MD

  Seoul National University Hospital

  STUDY DIRECTOR

• Kyung-Hee Kim, MD

  Seoul National University Hospital

  STUDY DIRECTOR

• Yeonyee E Yoon, MD

  Seoul National University Hospital

  STUDY DIRECTOR

Central Study Contacts

Yong-Jin Kim, MD, PhD

CONTACT

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

In-Chang Hwang, MD

CONTACT

82-10-5113-2395; inchang.hwang@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: May 13, 2012
• First Posted: May 15, 2012
• Study Start: October 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: May 1, 2013
• Last Updated: January 31, 2013

Record last verified: 2013-01

Locations

KR (2)