Understanding of Chest Pain in Microvascular Disease Proved by Cardiac Magnetic Resonance Image (UMPIRE)

Current therapeutic options for a well-recognized group of patients with anginal symptoms-a positive exercise tolerance testing, SPECT or perfusion defect in MRI but angiographically normal coronary arteries-are limited. The condition, referred to as microvascular angina (MVA) or cardiac syndrome X, is not as benign as originally reported-patients presenting with unstable angina and nonobstructive atherosclerotic coronary artery disease have a 2% risk of death or myocardial infarction at 30 days of follow-up. It is more common in women in whom the first presentation of angina occurs either perimenopausally or postmenopausally. Aberrant flow-mediated coronary vasomotion is pivotal in the pathogenesis (systemic) impairment in endothelial function. Indeed, some centers use systemic assessments of vascular function in their diagnostic pathways for this group of women. It was recently suggested that endothelial dysfunction may lead to myocardial ischemia.

In the present study, the investigators tested the hypothesis that udenafil offers dual benefits of improving vascular function and lessening ischemia in women with angina, perfusion defect in cardiac MRI, and normal coronary arteries.

Study Overview

• Status: Unknown
• Conditions: Microvascular Angina
• Intervention / Treatment: Drug: placebo; Drug: Udenafil

Detailed Description

The aim of this study is that udenafil offers dual benefits of improving vascular function and lessening ischemia in women with microvascular angina, perfusion defect in cardiac MRI, and normal coronary arteries.

The UMPIRE trial is a multi-center, prospective, randomized, placebo controlled trial, designed to evaluate the effect of udenafil in improvement of myocardial stress perfusion defect in cardiac MRI, in women patients with microvascular angina. A total of 70 patients will be randomized to udenafil(100 mg q d) or placebo treatment. The primary end point of the study is Change of perfusion defect over 25% of baseline defect in adenosine-stress cardiac MRI after 3-month treatment. The secondary endpoints of this study are change of perfusion defect less than 25% of baseline defect in adenosine-stress cardiac MRI after 3-month treatment, decrement of frequency of chest pain, improvement of ST-depression in stress test, improvement of duke score in stress test, improvement of QoL assessment by SF-36 questionnaire, improvement of sexual dysfunction assessment by BISF-W self-questionnaire and improvement of biomarkers foe endothelial function.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seongnam, Korea, Republic of
    • Recruiting
    • Seoul National University Bundang Hospital
    • Contact: Dong-Ju Choi, M.D.,Ph.D.; Phone Number: 82-31-787-7007; Email: djchoi@snu.ac.kr
    • Principal Investigator: Dong-Ju Choi, M.D.,Ph.D.
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Korea University Guro Hospital
    • Contact: Eng-Ju Kim, M.D.,Ph.D.
    • Principal Investigator: Eng-Ju Kim, M.D.,Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. MVA patients with typical symptom and positive adenosine-stress cardiac MRI and with normal coronary artery in coronary angiogram or coronary artery CT angiography.
2. Definition of positive adenosine-stress MRI: perfusion defect > 25% of transmurality ( by 2 radiologist based on visual assessment and qualitative assessment in core-lab)
3. Gender: female
4. Age: 18-80

Exclusion Criteria:

1. The patient with contraindication to MR contrast media or MR Imaging
2. LVEF < 50%
3. Any heart rhythm abnormality other than sinus rhythm
4. Valvular heart disease with more than moderate degree
5. Renal failure
6. Congestive Heart Failure
7. Myocardial infraction
8. Myocarditis
9. Congenital heart disease
10. Pericarditis
11. Variant angina (positive provocation test with Ergonovine or acetylcholine)
12. GERD (conformed by esophagogastroduodenoscopy)
13. Pregnant women with suspected, pregnant women or women with lactation
14. QT prolongation syndrome or take drugs that prolong the QT interval - Antiarrhythmics class IA; quinidine, procainamide - Antiarrhythmics class III; amiodarone, sotalol

15. Preanalytical within 30 days of screening in a clinical trial that may affect the influence of udenafil

    - Other PDE5 inhibitors (ex. Sildenafil, tadalafil)

    - Nitrates/ NO donor (ex. Nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, amyl nitrate/nitrite, sodium nitroprusside, nicorandil)

16. Preanalytical within 7 days of screening in a clinical trial that may affect the metabolism of udenafil

    • Antibacterials (ex. Erythromycin)
    • Antifungals (ex. Itraconazole, ketoconazole)
    • Antivirals (ex. Ritonavir, saquinavir, amprenavir, indinavir, nelfinavir)
    • Cimetidine
    • Grapefruit juice

17. Allergy or sensitivity with PDE 5 inhibitors

    -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Udenafil; 70 subjects will undergo baseline testing and then be randomized into a clinical parallel trial of udenafil 100mg or placebo po q d for 3 months.	Drug: Udenafil; 70 subjects will undergo baseline testing and then be randomized into a clinical parallel trial of udenafil 100mg po q d for 3 months.; Other Names: Zydena
Placebo Comparator: Placebo; 70 subjects will undergo baseline testing and then be randomized into a clinical parallel trial of udenafil 100mg or placebo po q d for 3 months.	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
to change of perfusion defect over 25% of baseline defect in adenosine-stress cardiac MRI after 3-month treatment.	baseline, 3 months after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
to change of perfusion defect less than 25% of baseline defect in adenosine-stress cardiac MRI after 3-month treatment	baseline, 3 months after treatment

Other Outcome Measures

Outcome Measure	Time Frame
to change of frequency of chest pain	baseline, 3 months after treatment
to change of improvement of ST-depression in ECG	baseline, 3 months after treatment
to change of QoL(Quality of Life)	baseline, 3 months after treatment
to change of sexual dysfunction	baseline, 3 months after treatment
to change of improvement of biomarkers for endothelial function	baseline and 3 months after treatment

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Sung-Ji Park, M.D.,Ph.D., Samsung Medical Center

Publications and helpful links

General Publications

• Park SJ, Park JJ, Choi DJ, Chun EJ, Choi SI, Kim SM, Jang SY, Ahn S, Choe YH. Understanding of chest pain in microvascular disease proved by cardiac magnetic resonance image (UMPIRE): study protocol for a randomized controlled trial. Trials. 2014 Aug 26;15:333. doi: 10.1186/1745-6215-15-333.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: November 20, 2012
• First Submitted That Met QC Criteria: January 15, 2013
• First Posted (Estimate): January 16, 2013

Study Record Updates

• Last Update Posted (Estimate): March 26, 2014
• Last Update Submitted That Met QC Criteria: March 24, 2014
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Ischemia; Cardiac MRI; Heart disease; microvascular angina; PDE-5 inhibitors
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Angina Pectoris; Chest Pain; Microvascular Angina; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Udenafil
• Other Study ID Numbers: 2011-07-048