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)

Phase 2

Completed

Conditions: Coronary Artery Disease (CAD)

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

Registration Number: NCT01334918

Lead Sponsor: Astellas Pharma Inc

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 124

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Single Photon Emission Computed Tomography (SPECT)	Contrast	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.
Single Photon Emission Computed Tomography (SPECT)	Multidetector Computed Tomography	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.
Single Photon Emission Computed Tomography (SPECT)	technetium Tc99m sestamibi /technetium Tc99m tetrafosmin	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.
Single Photon Emission Computed Tomography (SPECT)	Single Photon Emission Computed Tomography	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.
Multidetector Computed Tomography (MDCT)	Contrast	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.
Multidetector Computed Tomography (MDCT)	technetium Tc99m sestamibi /technetium Tc99m tetrafosmin	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.
Multidetector Computed Tomography (MDCT)	Single Photon Emission Computed Tomography	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.
Multidetector Computed Tomography (MDCT)	Multidetector Computed Tomography	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.
Single Photon Emission Computed Tomography (SPECT)	regadenoson	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.
Multidetector Computed Tomography (MDCT)	regadenoson	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Reversible Defects	Day 1 and Day 2	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.

Secondary Outcome Measures

Name	Time	Method
Overall Image Quality of Scans by Modality and Reviewer	Day 1 and Day 2	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).
Number of Participants With Reversible Defects in the Left Anterior Descending Coronary Artery (LAD)	Day 1 and Day 2	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.
Number of Participants With Reversible Defects in the Right Coronary Artery (RCA)	Day 1 and Day 2	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.
Number of Participants With Reversible Defects in the Left Circumflex Coronary Artery (LCX)	Day 1 and Day 2	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.
Number of Participants With Fixed Defects	Day 1 and Day 2	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.
Percentage of Participants With Two or More Ischemic Segments on SPECT, But Less on CT	Day 1 and Day 2	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.

Trial Locations

Locations (11): Cardiovascular Research Center of South Florida
🇺🇸
Miami, Florida, United States
Baptist Hospital of Miami
🇺🇸
Miami, Florida, United States
Harbor UCLA Medical Center
🇺🇸
Torrance, California, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Berkshire Medical Center
🇺🇸
Pittsfield, Massachusetts, United States
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States
Midwest Cardiology Associates, P.C.
🇺🇸
Overland Park, Kansas, United States
Sutter Roseville Medical Center
🇺🇸
Roseville, California, United States
Maine Research Associates
🇺🇸
Auburn, Maine, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States