The purpose of this study is to assess the effect of febuxostat on coronary artery flow in patients with coronary artery disease.
The drug being tested in this study is called febuxostat. Febuxostat is being tested to treat people who have angina. This study will look at the heart and blood flow of people who take febuxostat. The study will enroll approximately 30 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups (or sequences)-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): * Sequence 1: 6 weeks febuxostat followed by 6 weeks of placebo. * Sequence 2: 6 week placebo followed by 6 weeks of febuxostat All participants will be asked to take one capsule at the same time each day throughout the study. All participants will be asked to record any time they have angina symptoms during the study. This single-center trial will be conducted in the United States. The overall time to participate in this study is 16 weeks. Participants will make 7 visits to the clinic including a final visit 4 weeks after last dose of study drug for a follow-up assessment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
30
Febuxostat capsules
Febuxostat placebo-matching capsules
Unnamed facility
Baltimore, Maryland, United States
Change in Coronary Artery Flow From Rest to Isometric Handgrip (IHG) Exercise at the End of the Administration of Febuxostat and Placebo
Coronary artery flow was measured using magnetic resonance imaging (MRI) at rest and during sustained isometric (static) handgrip exercises. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Time frame: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)
Change in Coronary Artery Cross-Sectional Area From Rest to IHG Exercise at the End of the Administration of Febuxostat and Placebo
Coronary artery cross-sectional area was measured by MRI at rest and during sustained isometric (static) handgrip exercise. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Time frame: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)
Change in Coronary Flow Velocity From Rest to IHG Exercise at the End of the Administration of Febuxostat and Placebo
Coronary flow velocity was measured by MRI at rest and during sustained isometric (static) handgrip exercise. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Time frame: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)
Change in Coronary Artery Flow Following the Administration of Sublingual Nitroglycerin at the End of the Administration of Febuxostat and Placebo
Coronary artery flow was measured by MRI before and following administration of nitroglycerin under the tongue. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Time frame: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)
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Change in Coronary Artery Cross Sectional Area Following the Administration of Sublingual Nitroglycerin at the End of the Administration of Febuxostat and Placebo
Coronary artery cross sectional area was measured by MRI before and following administration of nitroglycerin under the tongue. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Time frame: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)
Change in Coronary Flow Velocity Following the Administration of Sublingual Nitroglycerin at the End of the Administration of Febuxostat and Placebo
Coronary flow velocity was measured by MRI before and following administration of nitroglycerin under the tongue. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Time frame: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)
Change in Time to Onset of ≥1 mm ST-Segment Depression During Exercise Treadmill Test (ETT)
Time in seconds to ischemic ECG changes during ETT. Continuous electrocardiography (ECG) was performed during an exercise treadmill test (modified Bruce protocol) to assess the onset of ST-segment depression after administration of febuxostat or placebo for 6 weeks in participants with a normal ST segment at randomization. . Data at the end of each treatment period was combined for the febuxostat and the placebo arms.
Time frame: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)
Change in Maximum ST-segment Depression During Exercise Treadmill Test
Continuous ECG was performed during an exercise treadmill test (modified Bruce protocol) to assess the maximum ST-segment depression after 6 weeks of febuxostat or placebo treatment in participants with a normal ST segment at randomization. A negative change from Baseline indicates improvement. Data at the end of each treatment period was combined for the febuxostat and the placebo arms.
Time frame: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)
Percentage of Participants Stopping Exercise Treadmill Test Due to Angina at the End of the Administration of Febuxostat and Placebo
An exercise treadmill test (modified Bruce protocol) was performed. Data at the end of each treatment period was combined for the febuxostat and the placebo arms.
Time frame: At the end of each 6 week treatment period (Week 6 and Week 12)
Time to Onset of Angina During Exercise Treadmill Test at the End of the Administration of Febuxostat and Placebo
Time in seconds to ischemic chest pain/ angina during ETT. Data at the end of each period was combined for the febuxostat and the placebo arms
Time frame: At the end of each 6 week treatment period (Week 6 and Week 12)
Exercise Duration
Exercise duration is the exercise time in seconds during ETT. Data at the end of each period was combined for the febuxostat and the placebo arms.
Time frame: At the end of each 6 week treatment period (Week 6 and Week 12)