A Study of Regadenoson in Subjects Undergoing Stress Myocardial Perfusion Imaging (MPI) Using Multidetector Computed Tomography (MDCT) Compared to Single Photon Emission Computed Tomography (SPECT)

Study Overview
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Brief Summary
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The purpose of this study is to compare Multidetector Computed Tomography (MDCT) and Single Photon Emission Computed Tomography (SPECT) stress myocardial perfusion imaging (MPI) with regadenoson in order to detect the presence or absence of reversible defects.

Detailed Description
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All participants will be randomized to one of two imaging sequences: rest/stress SPECT on Day 1 followed by stress/rest MDCT on Day 2 or stress/rest MDCT on Day 1 followed by rest/stress SPECT on Day 2. All stress scans will involve the injection of regadenoson as the pharmacologic stress agent.

Official Title
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A Phase 2, Open-Label, Randomized, Cross-Over Study of Regadenoson in Subjects Undergoing Stress Myocardial Perfusion Imaging by Multidetector Computed Tomography (MDCT) and Single Photon Emission Computed Tomography (SPECT)

Conditions
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Coronary Artery Disease (CAD)

Intervention / Treatment
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* Drug: regadenoson
* Radiation: technetium Tc99m sestamibi /technetium Tc99m tetrafosmin
* Radiation: Contrast
* Procedure: Single Photon Emission Computed Tomography
* Procedure: Multidetector Computed Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects must be ≥ 45 years of age Female subjects must be ≥ 50 years of age Subject has met at least one of the following three criteria: has a suspected (clinical impression) or known diagnosis of coronary artery disease (CAD) with typical angina that has been referred from nuclear cardiology lab schedule or cardiac computed tomography (CT) schedule has stable symptoms with possible elective catheterization procedure scheduled and where further imaging may be beneficial; has known CAD from a previous invasive coronary angiography (ICA) performed more than 12 weeks prior to screening who now present with new cardiac symptoms Subject has been referred for a clinically indicated myocardial perfusion imaging procedure or Cardiac CT procedure for suspected moderate or high risk CAD Subject must abstain from eating and drinking 30 minutes prior and 30 minutes post study drug administration Subject must abstain from smoking 3 hours prior and 8 hours post study drug administration Subject must abstain from any intake of methylxanthine-containing foods and beverages within 12 hours prior to Day 1 visit through the Day 3 Follow-Up Visit, as these foods may alter regadenoson effects. Subject is able to safely abstain from theophylline use for 12 hours prior to study drug administration Exclusion Criteria: Subject is concurrently participating in another drug study or has received an investigational drug within 30 days prior to Screening Subject has a history of a clinically significant illness (other than CAD), medical condition, or laboratory abnormality, which would preclude participation in the study Subject has renal dysfunction demonstrated by a glomerular filtration rate (GFR) < 45 mL/min (calculated using Cockroft-Gault formula Note: Subjects with a GFR 45-60 mL/min will undergo a hydration procedure Female subject who is pregnant, lactating or of childbearing potential that refuses to use a medically acceptable form of contraception until the Telephone Follow up Visit is complete Female subject has a positive pregnancy test prior to randomization Subject has a history of second or third degree heart block or sinus node dysfunction unless the subject has a functioning pacemaker Subject has symptomatic hypotension (temporary and reversible conditions that no longer exist are allowed) Subject is allergic or intolerant to aminophylline, nitroglycerin or metoprolol Subject is allergic or intolerant to regadenoson or any of its excipients Subject is unable or unwilling to comply with the procedure schedule Subject has previously enrolled in this study or was enrolled in another regadenoson study sponsored by Astellas Subject has atrial fibrillation or significant arrhythmias which may result in decreased image quality for the imaging studies (CT and SPECT) Subject has high heart rate (> 65 beats per minute) and contra-indications to administer beta-blockers (severe chronic obstructive pulmonary disease (COPD) or asthma, second and third degree atrioventricular block)

Ages Eligible for Study
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Minimum Age: 45 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Photon Emission Computed Tomography (SPECT)<br>Resting SPECT imaging was performed prior to regadenoson stress SPECT imaging. Imaging was conducted with one of two radiotracers (99mTc sestamibi or tetrofosmin). Regadenoson 0.4 mg was administered prior to stress SPECT as a single bolus injection. | Drug: regadenoson<br>* Administered by intravenous bolus.<br>* Other names: Lexiscan;Radiation: technetium Tc99m sestamibi /technetium Tc99m tetrafosmin<br>* Administered by intravenous infusion<br>* Other names: Myoview;Radiation: Contrast<br>* Administered by intravenous infusion.<br>Procedure: Single Photon Emission Computed Tomography<br>* Procedure/Surgery<br>Procedure: Multidetector Computed Tomography<br>* Procedure/Surgery<br>|
| Experimental: Multidetector Computed Tomography (MDCT)<br>Multidetector Computed Tomography (MDCT), composed of CCTA and regadenoson CTP. Regadenoson stress CTP was performed prior to rest CCTA/CTP imaging. Regadenoson 0.4 mg was administered prior to stress CTP as a single bolus injection. The rest CCTA/CTP was performed at least 30 minutes after completion of the stress CTP, after resolution of any symptoms brought on by the regadenoson infusion and after the participant's heart rate had returned to baseline. | Drug: regadenoson<br>* Administered by intravenous bolus.<br>* Other names: Lexiscan;Radiation: technetium Tc99m sestamibi /technetium Tc99m tetrafosmin<br>* Administered by intravenous infusion<br>* Other names: Myoview;Radiation: Contrast<br>* Administered by intravenous infusion.<br>Procedure: Single Photon Emission Computed Tomography<br>* Procedure/Surgery<br>Procedure: Multidetector Computed Tomography<br>* Procedure/Surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Reversible Defects | The number of reversible defects categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from the 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of 2 or more segments with reversible defects, excluding segment 17. | Day 1 and Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Image Quality of Scans by Modality and Reviewer | Overall image quality was assessed by three independent blinded readers for each modality (single photon emission computed tomography (SPECT) and multidetector computed tomography (MDCT)). Image quality was rated on a 4-point scale as either excellent, good, fair or poor at rest using SPECT and MDCT and under stress using regadenoson SPECT and regadenoson stress computed tomography perfusion (CTP). | Day 1 and Day 2 | 
| Number of Participants With Reversible Defects in the Left Anterior Descending Coronary Artery (LAD) | The number of reversible defects in the LAD categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of ≥ 2 segments with reversible defects, excluding segment 17. | Day 1 and Day 2 | 
| Number of Participants With Reversible Defects in the Right Coronary Artery (RCA) | The number of reversible defects in the RCA categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of ≥ 2 segments with reversible defects, excluding segment 17. | Day 1 and Day 2 | 
| Number of Participants With Reversible Defects in the Left Circumflex Coronary Artery (LCX) | The number of reversible defects in the LCX categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of ≥ 2 segments with reversible defects, excluding segment 17. | Day 1 and Day 2 | 
| Number of Participants With Fixed Defects | Using the 17-segment scoring system, a segment scored above 1 (i.e., 2 to 4) and equal at rest and stress was counted as having a fixed defect. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. | Day 1 and Day 2 | 
| Percentage of Participants With Two or More Ischemic Segments on SPECT, But Less on CT | Using SPECT as the reference standard, the false negative percentage was calculated as the percentage of participants with two or more ischemic segments on SPECT, but less on CT. | Day 1 and Day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacologic stress, Coronary Artery Disease (CAD), regadenoson, ischemia