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)

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)

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease (CAD)
• Intervention / Treatment: Drug: regadenoson; Radiation: technetium Tc99m sestamibi /technetium Tc99m tetrafosmin; Radiation: Contrast; Procedure: Single Photon Emission Computed Tomography; Procedure: Multidetector Computed Tomography

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.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Torrance, California, United States, 90502
      • Harbor UCLA Medical Center
  • Florida
    • Miami, Florida, United States, 33176
      • Baptist Hospital of Miami
    • Miami, Florida, United States, 33173
      • Cardiovascular Research Center of South Florida
  • Kansas
    • Overland Park, Kansas, United States, 66029
      • Midwest Cardiology Associates, P.C.
  • Maine
    • Auburn, Maine, United States, 04210
      • Maine Research Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Pittsfield, Massachusetts, United States, 01201
      • Berkshire Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Photon Emission Computed Tomography (SPECT); 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; Administered by intravenous bolus.; Other Names: Lexiscan; CVT 3146; Radiation: technetium Tc99m sestamibi /technetium Tc99m tetrafosmin; Administered by intravenous infusion; Other Names: Cardiolite; Myoview; Radiation: Contrast; Administered by intravenous infusion.; Procedure: Single Photon Emission Computed Tomography; Procedure/Surgery; Procedure: Multidetector Computed Tomography; Procedure/Surgery
Experimental: Multidetector Computed Tomography (MDCT); 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; Administered by intravenous bolus.; Other Names: Lexiscan; CVT 3146; Radiation: technetium Tc99m sestamibi /technetium Tc99m tetrafosmin; Administered by intravenous infusion; Other Names: Cardiolite; Myoview; Radiation: Contrast; Administered by intravenous infusion.; Procedure: Single Photon Emission Computed Tomography; Procedure/Surgery; Procedure: Multidetector Computed Tomography; Procedure/Surgery

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Senior Medical Director, Astellas Pharma Global Development

Publications and helpful links

General Publications

• Cury RC, Kitt TM, Feaheny K, Akin J, George RT. Regadenoson-stress myocardial CT perfusion and single-photon emission CT: rationale, design, and acquisition methods of a prospective, multicenter, multivendor comparison. J Cardiovasc Comput Tomogr. 2014 Jan-Feb;8(1):2-12. doi: 10.1016/j.jcct.2013.09.004. Epub 2013 Oct 18.

Helpful Links

• Link to results on the Astellas Clinical Study Results website.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2011
• Primary Completion (Actual): July 2, 2012
• Study Completion (Actual): July 2, 2012

Study Registration Dates

• First Submitted: April 12, 2011
• First Submitted That Met QC Criteria: April 12, 2011
• First Posted (Estimated): April 13, 2011

Study Record Updates

• Last Update Posted (Actual): December 4, 2024
• Last Update Submitted That Met QC Criteria: November 12, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: ischemia; regadenoson; Coronary Artery Disease (CAD); pharmacologic stress
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Neurotransmitter Agents; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine A2 Receptor Agonists; Technetium Tc 99m Sestamibi; Regadenoson
• Other Study ID Numbers: 3606-CL-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR