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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01334918
First received: April 12, 2011
Last updated: July 11, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease (CAD)
Drug: regadenoson
Radiation: technetium Tc99m sestamibi /technetium Tc99m tetrafosmin
Radiation: Contrast
Procedure: Single Photon Emission Computed Tomography
Procedure: Multidetector Computed Tomography
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Number of Participants With Reversible Defects [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]

    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:
  • Overall Image Quality of Scans by Modality and Reviewer [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]
    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.


Enrollment: 124
Study Start Date: April 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • CVT 3146
  • Lexiscan
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: Multidetector Computed Tomography
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:
  • CVT 3146
  • Lexiscan
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: 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.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01334918

Locations
United States, California
Sutter Roseville Medical Center
Roseville, California, United States, 95661
Harbor UCLA Medical Center
Torrance, California, United States, 90502
United States, Florida
Cardiovascular Research Center of South Florida
Miami, Florida, United States, 33173
Baptist Hospital of Miami
Miami, Florida, United States, 33176
United States, Kansas
Midwest Cardiology Associates, P.C.
Overland Park, Kansas, United States, 66029
United States, Maine
Maine Research Associates
Auburn, Maine, United States, 04210
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Berkshire Medical Center
Pittsfield, Massachusetts, United States, 01201
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Senior Medical Director Astellas Pharma Global Development
  More Information

No publications provided by Astellas Pharma Inc

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01334918     History of Changes
Other Study ID Numbers: 3606-CL-2001
Study First Received: April 12, 2011
Results First Received: July 11, 2013
Last Updated: July 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Coronary Artery Disease (CAD)
ischemia
pharmacologic stress
regadenoson

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Technetium Tc 99m Sestamibi
Regadenoson
Radiopharmaceuticals
Diagnostic Uses of Chemicals
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action
Adenosine A2 Receptor Agonists
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014