Understanding of chest pain in microvascular disease proved by cardiac magnetic resonance image (UMPIRE): study protocol for a randomized controlled trial

BACKGROUND: Microvascular angina (MVA) is characterized by anginal chest pain, an abnormal stress test, and normal coronary arteries on coronary angiography. Although the exact pathogenesis remains unclear, endothelial dysfunction is a contributing factor. To date, there exists no specific therapy for this disease. Phosphodiesterase-5 inhibitor improves the endothelial function and subsequently microvascular circulation. The aim of this study is to identify whether udenafil offers benefits in the treatment of MVA in female patients, who have a perfusion defect in their cardiac magnetic resonance image (CMR), but normal coronary arteries. METHODS/DESIGN: The ‘Understanding of Chest Pain in Microvascular Disease Proved by Cardiac Magnetic Resonance Image: (UMPIRE)’ trial is a multicenter, prospective, randomized, placebo controlled trial, designed to evaluate the effect of udenafil on myocardial ischemia and symptoms in female patients with MVA. The myocardial ischemia will be quantified by myocardial stress perfusion defect in CMR. A total of 80 patients with proven perfusion defect in adenosine-stress CMR will be randomly assigned to either the udenafil treatment group (daily dose of 100 mg) or the placebo group for three months. The primary endpoint is >25% improvement in perfusion defect size in adenosine-stress CMR from baseline. The secondary endpoints include <25% improvement in perfusion defect size, chest pain frequency, ST depression in stress test, Duke score in stress test, quality of life (QoL) assessment by SF-36 questionnaire, sexual dysfunction assessment by BISF-W (Brief Index of Sexual Functioning for Women) self-assessment questionnaire, and biomarkers for endothelial function. DISCUSSION: The UMPIRE trial is the first randomized controlled trial to evaluate the efficacy of udenafil in female MVA patients. If udenafil demonstrates cardioprotective effects, it may provide a novel therapeutic option to reduce myocardial ischemia and improve cardiac function in female MVA patients. TRIAL REGISTRATION: Clinical Trials.gov: NCT01769482 (registered on 20 November 2012).