Regadenoson Combined With Symptom-Limited Exercise in Patients Undergoing Myocardial Perfusion Imaging

Study Overview
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Brief Summary
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Not infrequently, a physician is faced with uncertainty regarding the ability of a patient to perform adequate exercise in the noninvasive evaluation of known or suspected coronary artery disease (CAD) by the use of radionuclide stress myocardial perfusion imaging. In selected patients, protocols that combine exercise (either low-level or symptom-limited) with vasodilator stress agents have been found to be safe and effective in both identification of the presence and severity of CAD as well as risk stratification for adverse cardiac outcome. However, currently utilized combined stress protocols have drawbacks. Further refinement of combined stress protocols would potentially lead to more appropriate stress protocol selection for patients while enhancing laboratory efficiency. The purpose of this prospective, randomized study will be to evaluate the relative merits of combining regadenoson with symptom-limited exercise in patients clinically-referred for vasodilator-exercise stress myocardial perfusion imaging for the assessment of known or suspected CAD. It is hypothesized that combining regadenoson with symptom-limited exercise is a safe and feasible stress testing modality which is non-inferior to that which combines symptom-limited exercise with dipyridamole.

Official Title
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The Ex-Lex Trial: A Randomized Trial Combining Regadenoson With Symptom-Limited Exercise in Patients Undergoing Myocardial Perfusion Imaging

Conditions
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Coronary Artery Disease, Myocardial Ischemia

Intervention / Treatment
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* Drug: Regadenoson
* Other: Symptom-limited exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant, non-nursing females clinically referred for vasodilator stress myocardial perfusion imaging with the addition of exercise Age >=30 years Exclusion Criteria: Extremely limited functional capacity Age <30 years Unable or unwilling to provide informed consent Pregnant or nursing females Current use of methylxanthines within 12 hours of testing Current use of dipyridamole or aminophylline within 48 hours of testing Uncontrolled hypertension (>200 mmHg systolic/>120 mmHg diastolic) Known hypertrophic cardiomyopathy with obstruction or severe aortic stenosis Decompensated congestive heart failure History of sick sinus syndrome or > first degree atrioventricular block in the absence of a functioning pacemaker Asthma or other bronchospastic reactive airway disease History of percutaneous coronary intervention or coronary artery bypass grafting, or documented history of acute myocardial infarction or unstable angina within one week of testing Patients at risk for hypotensive reaction to regadenoson

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vasodilator-exercise stress<br>Four-minute infusion of dipyridamole (0.56 mg/kg) followed by symptom-limited exercise; injection of technetium-99m labeled radiopharmaceutical at peak hyperemia or peak exercise followed by SPECT myocardial perfusion imaging | Other: Symptom-limited exercise<br>* Dipyridamole (0.56 mg/kg) over 4 minutes followed by symptom-limited exercise with technetium-99m SPECT myocardial perfusion imaging<br>* Other names: Persantine-exercise stress test;|
| Experimental: Exercise-vasodilator stress<br>Symptom-limited exercise followed by a bolus intravenous injection of regadenoson (0.4 mg/5 mL) in patients failing to achieve a standard clinical endpoint; injection of technetium-99m labeled radiopharmaceutical 15 seconds after administration of regadenoson (or at peak exercise if regadenoson not administered) followed by SPECT myocardial perfusion imaging. | Drug: Regadenoson<br>* Regadenoson (0.4mg/5 mL) injection during symptom-limited exercise with technetium-99m SPECT myocardial perfusion imaging<br>* Other names: Exercise-lexiscan stress test;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Major Adverse Events or Side Effects Graded Severe on Symptom Questionnaire | Number of participants with any side effect (flushing, shortness of breath, headache, chest discomfort, dizziness, nausea, or abdominal pain) requiring specific treatment or graded as severe by the patient; or any death, myocardial infarction, or unplanned hospitalization. Note that 2 patients allocated to exercise-vasodilator stress did not complete symptom questionnaires and are therefore excluded from analysis. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Perfusion Image Quality | Single photon emission computed tomography myocardial perfusion acquisition and image processing was performed in accordance with American Society of Nuclear Cardiology guidelines. All images were interpreted by consensus read of three investigators blinded to stress test protocol and results. Overall perfusion and gated image quality were described as excellent (no artifacts interfering with myocardial perfusion interpretation), good, fair, or poor (artifact requiring reprocessing or repeat imaging of the patient to allow for diagnostic interpretation). | 0 hours |