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

Seoul National University

Status and phase

Unknown

Phase 3

Conditions

Mild Pulmonary Hypertension

Treatments

Drug: Udenafil (Zydena)

Drug: Placebo

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01696240

H-1202-005-396

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

40 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

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.

Treatment:

Drug: Placebo

Udenafil

Active Comparator group

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.

Treatment:

Drug: Udenafil (Zydena)