A Study to Assess Regadenoson Administration Following an Inadequate Exercise Stress Test as Compared to Regadenoson Alone for Myocardial Perfusion Imaging (MPI) Using Single Photon Emission Computed Tomography (SPECT) (EXERRT)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT01618669
First received: May 29, 2012
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to demonstrate that the strength of agreement between single photon emission computed tomography (SPECT) imaging with regadenoson following inadequate exercise stress testing and SPECT imaging with regadenoson alone is not inferior to the strength of agreement between two sequential regadenoson SPECT images without exercise.


Condition Intervention Phase
Coronary Artery Disease (CAD)
Drug: Regadenoson
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Phase 3b, Open-Label, Parallel Group, Randomized, Multicenter Study to Assess Regadenoson Administration Following an Inadequate Exercise Stress Test as Compared to Regadenoson Alone for Myocardial Perfusion Imaging (MPI) Using Single Photon Emission Computed Tomography (SPECT)

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Majority Agreement- Yes or Majority Agreement No (using number of segments with reversible defects categorized as absence (0-1) or presence (≥2) of ischemia as assessed by each of the three blinded independent expert readers) [ Time Frame: Visit 2 (Day 1) and Visit 3 (Day 2 up to Day 15) ] [ Designated as safety issue: No ]
    Each reader will be defined as having self-agreement based upon identical categorization of a given subject as absent or present for ischemia for both the initial and second stress visits. A given subject will be defined as having a majority agreement if at least 2 out of the 3 blinded readers demonstrate self-agreement.


Secondary Outcome Measures:
  • Percentage of subjects who experience at least one treatment emergent clinically significant cardiac event [ Time Frame: within 1 hour (events found on electrocardiogram (ECG)) up to 24 hours (adverse events) after administration of regadenoson ] [ Designated as safety issue: Yes ]
    The significant cardiac events are: number of ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation) ST-T depression (>2 mm); ST-T elevation (>1 mm), incidence of atrioventricular (AV) block; sinus arrest > 3 seconds in duration found on ECG, TEAE of unstable angina or myocardial infarction.

  • Agreement rates between SPECT imaging with regadenoson following inadequate exercise stress testing and SPECT imaging with regadenoson alone [ Time Frame: Visit 2 (Day 1) and Visit 3 (Day 2 up to Day 15) ] [ Designated as safety issue: No ]
    3 categories for ischemia (0-1, 2-4, ≥ 5 reversible segments) and 2 categories for ischemia (0-1, ≥ 2 reversible segments) based on the median count of the number of reversible defects across the three blinded independent expert readers will be used.

  • Agreement of image pairs with regard to reader summed difference score (SDS) and summed stress score (SSS) and a paired (side by side) comparison of ischemic extent [ Time Frame: Visit 2 (Day 1) and Visit 3 (Day 2 up to Day 15) ] [ Designated as safety issue: No ]
  • Overall assessment of image quality between scans obtained with regadenoson myocardial perfusion imaging (MPI) and regadenoson exercise MPI [ Time Frame: Visit 2 (Day 1) and Visit 3 (Day 2 up to Day 15) ] [ Designated as safety issue: No ]
    Image quality is defined by the independent readers as excellent, good, fair or poor

  • Target (heart) to background radiotracer ratio of the heart to liver and heart to gut between regadenoson MPI and regadenoson exercise MPI [ Time Frame: Visit 2 (Day 1) and Visit 3 (Day 2 up to Day 15) ] [ Designated as safety issue: No ]
  • Target (heart) to background radiotracer ratio of the combined background ratio of gut and liver (mean of gut and liver) between regadenoson MPI and regadenoson exercise MPI [ Time Frame: Visit 2 (Day 1) and Visit 3 (Day 2 up to Day 15) ] [ Designated as safety issue: No ]
  • Sub diaphragmatic radiotracer activity interference with cardiac image quality using a 4-point scale between regadenoson MPI and regadenoson exercise MPI [ Time Frame: Visit 2 (Day 1) and Visit 3 (Day 2 up to Day 15) ] [ Designated as safety issue: No ]
    The 4-point scale is comprised of the following categories: None, Slight, Moderate and Severe

  • Cardiac segments obscured by the sub diaphragmatic activity between regadenoson MPI and regadenoson exercise MPI [ Time Frame: Visit 2 (Day 1) and Visit 3 (Day 2 up to Day 15) ] [ Designated as safety issue: No ]
  • Percentage of subjects experiencing one or more treatment-emergent adverse events (TEAE) within 2 hours after administration of regadenoson [ Time Frame: up to 2 hours after study drug ] [ Designated as safety issue: Yes ]
  • Percentage of subjects experiencing one or more TEAEs within 24 hours after administration of regadenoson [ Time Frame: up to 24 hours after study drug ] [ Designated as safety issue: Yes ]
  • Changes in heart rate (HR) from baseline to each scheduled observation and to highest observed value within 1 hour after regadenoson administration as assessed by ECG [ Time Frame: Baseline and up to 1 hour after study drug administration ] [ Designated as safety issue: Yes ]
    Baseline is on Visit 2 (Day 1)

  • Percent of subjects with HR >100 bpm [ Time Frame: Baseline and post baseline (Visit 2 and Visit 3) ] [ Designated as safety issue: Yes ]
    Baseline is on Visit 2 (Day 1). Visit 3 is between Day 2 and Day 15

  • Percent of subjects with HR increase > 40 bpm [ Time Frame: Baseline and post baseline (Visit 2 and Visit 3) ] [ Designated as safety issue: Yes ]
    Baseline is on Visit 2 (Day 1). Visit 3 is between Day 2 and Day 15

  • Proportion of subjects with vital sign changes [ Time Frame: Baseline and post baseline (Visit 2 and Visit 3) ] [ Designated as safety issue: Yes ]
    Baseline is on Visit 2 (Day 1). Visit 3 is between Day 2 and Day 15. Vital sign changes defined as a systolic blood pressure (SBP) decrease of 35 mmHg or more, a SBP less than 90 mmHg or more, SBP ≥ 200 mmHg, SBP ≥ 180 mmHg with an increase of 20 mmHg, an increase in SBP of ≥ 50 mmHg, diastolic blood pressure < 50 mmHg, decrease > 25 mmHg, ≥ 115 mmHg, or increase ≥ 30 mmHg

  • Radiation Exposure [ Time Frame: Baseline and post baseline (Visit 2 and Visit 3) ] [ Designated as safety issue: Yes ]
    Total radiation dose received by subjects


Enrollment: 1147
Study Start Date: June 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regadenoson After Peak Exercise Drug: Regadenoson
Intravenous (IV)
Other Name: Lexiscan, CVT3146
Active Comparator: Regadenoson Alone Drug: Regadenoson
Intravenous (IV)
Other Name: Lexiscan, CVT3146

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects referred for an exercise or pharmacologic stress test SPECT MPI procedure for the evaluation of coronary artery disease (CAD) are eligible for study participation. Subjects referred for pharmacologic stress should have a reasonable potential of attempting exercise stress. Subject must have one of the following:

    • a. Past ischemia on any prior imaging stress test without invasive intervention on the artery subtending this territory
    • b. Subject with known CAD who have symptoms similar to previous ischemic symptoms, or recent onset of symptoms or recently worsened symptoms suggestive of ischemia
    • c. Diamond Forrester estimated pretest probability of CAD of ≥ 50%
    • d. History of most recent coronary artery bypass surgery or most recent percutaneous coronary intervention (PCI) > 10 years (patients who are > 30 days but less than 10 years post coronary artery bypass graft (CABG) or PCI can be included if they meet criteria a, b, or e)
    • e. Previously demonstrated 100% occlusion by invasive coronary or computed tomography (CT) angiography without successful intervening revascularization as these foods may alter regadenoson effects

Exclusion Criteria:

  • Subject has a clinically significant illness, medical condition, or laboratory abnormality
  • Female subject who is pregnant or lactating
  • Subject is on dialysis for end stage renal disease or has a history of glomerular filtration rate (GFR) < 15 mL/min (calculated using MDRD [Modification of Diet in Renal Disease] formula)
  • Subject has a history of coronary revascularization by either PCI or CABG within 1 month prior to the rest myocardial perfusion imaging (MPI)
  • Subject has a pacemaker or an implantable cardioverter defibrillator (ICD)
  • Subject has a history of acute myocardial infarction (MI) or high risk unstable angina within 30 days prior to the rest MPI or has had cardiac transplantation
  • Subject has uncontrolled hypertension at any point on Visit 2 prior to exercise testing (i.e., systolic blood pressure (SBP) ≥ 180 or diastolic blood pressure (DBP) ≥ 95 mmHg on two consecutive measurements while at rest).
  • Subject has severe aortic stenosis or hypertrophic cardiomyopathy with obstruction or has decompensated congestive heart failure
  • Subject has a history of severe respiratory disease including: asthma, chronic obstructive pulmonary disease (COPD) or other bronchospastic reactive airway disease or who is on 24-hour continuous oxygen
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01618669

  Hide Study Locations
Locations
United States, Alabama
Mobile Heart Specialists, PC
Mobile, Alabama, United States, 36608
United States, California
Silicon Valley Medical Imaging
Fremont, California, United States, 94538
Long Beach Memorial Medical Center
Long Beach, California, United States, 90806
VA Greater Los Angeles Healthcare System
Los Angeles, California, United States, 90073
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Westside Medical Associates of Los Angeles
Los Angeles, California, United States, 90211
Ventura Clinical Trials
Malibu, California, United States, 90265
Mission Internal Medical Group
Mission Viejo, California, United States, 92691
VA San Diego Healthcare System
San Diego, California, United States, 92161
Santa Rosa Cardiology Medical Group, Inc.
Santa Rosa, California, United States, 95405
Los Angeles Biomedical Research Institute
Torrance, California, United States, 22908
United States, Connecticut
HOCC - New Britain Campus
New Britain, Connecticut, United States, 06050
Yale University
New Haven, Connecticut, United States, 06510
United States, Delaware
Alfieri Cardiology
Newark, Delaware, United States, 19713
Delaware Clinical Trials
Wilmington, Delaware, United States, 19808
United States, Florida
Elite Research and Clinical Trials
Aventura, Florida, United States, 33180
S & W Clinical Research
Fort Lauderdale, Florida, United States, 33306
Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
Florida Heart Associates
Fort Myers, Florida, United States, 33907
St. Luke's Cardiology St. Vincent's HealthCare
Jacksonville, Florida, United States, 32216
East Coast Institute for Research, LLC
Jacksonville, Florida, United States, 32216
Watson Medical Clinic/Lakeland Regional Medical Clinic
Lakeland, Florida, United States, 33805
MIMA Century Research Associates
Melbourne, Florida, United States, 32901
Cardiovascular Research Center of South Florida
Miami, Florida, United States, 33173
Florida Hospital/Cardiovascular Institute
Orlando, Florida, United States, 32803
University of South Florida
Tampa, Florida, United States, 33620
Cardiology Partners Clinical Research Institute
Wellington, Florida, United States, 33449
United States, Georgia
St. Joseph's Hospital
Atlanta, Georgia, United States, 30342
University Cardiology Associates, LLC
Augusta, Georgia, United States, 30901
South Coast Medical Group
Savannah, Georgia, United States, 31406
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Indiana
I U School of Medicine/ Krannert Institute of Cardiology
Indianapolis, Indiana, United States, 46202
United States, Kansas
Midwest Cardiology Associates
Overland Park, Kansas, United States, 66209
United States, Maine
Maine Research Associates
Portland, Maine, United States, 04210
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21207
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Berkshire Medical Center
Pittsfield, Massachusetts, United States, 01201
United States, Michigan
Henry Ford Hospital
Detriot, Michigan, United States, 48202
Wayne State University
Detroit, Michigan, United States, 48201
Michigan Heart
Ypsilanti, Michigan, United States, 48197
United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
Cardiology Associates of North Mississippi
Tupelo, Mississippi, United States, 38801
United States, Missouri
Cardiovascular Imaging Technologies
Kansas City, Missouri, United States, 64111
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
Alegent Health Research Center
Omaha, Nebraska, United States, 68124
Alegent Health Heart and Vascular Specialists
Omaha, Nebraska, United States, 68124
United States, Nevada
Las Vegas Radiology
Las Vegas, Nevada, United States, 89113
United States, New York
Laurelton Medical center
Laurelton, New York, United States, 11422
Columbia University Medical Center
New York, New York, United States, 10032
Westchester Medical Center-New York Medical College
Valhalla, New York, United States, 10595
Buffalo Cardiology & Pulmonary Associates, P.C.
Williamsville, New York, United States, 14221
United States, Pennsylvania
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Berks Cardiologists, Ltd.
Wyomissing, Pennsylvania, United States, 19610
United States, Texas
Katy Cardiology Associates
Katy, Texas, United States, 77493
Mission Research Institute LLC
New Braunfels, Texas, United States, 78130
West Houston Area Clinical Trial Consultants, LLC
Tomball, Texas, United States, 77375
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Roanoke Heart Institute, PC
Roanoke, Virginia, United States, 24014
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Argentina
Hospital Italiano Garibaldi
Rosario, Santa Fé, Argentina, S2000ODA
Instituto Oulton
Cordoba, Argentina, X5000JJS
Instituto de Cardiologia la Plata
La Plata, Argentina, B1925XAC
Hospital Italiano de La Plata
Provincia de Buenos Aires, Argentina, B1900AX
Sanatorio San Geronimo
Santa Fe, Argentina, S3001XAF
Peru
Instituto Nacional Cardiovascular de EsSalud
Lima, Peru
Hospital Arzobispo Loayza
Lima, Peru
Clinica Anglo Americana
Lima, Peru, Lima 27
Puerto Rico
VA Caribbean Healthcare System (672)
San Juan, Puerto Rico, 00921
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Senior Medical Director Astellas Pharma Global Development, Inc.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT01618669     History of Changes
Other Study ID Numbers: 3606-CL-3004
Study First Received: May 29, 2012
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Peru: Instituto Nacional de Salud
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs

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

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Regadenoson
Adenosine A2 Receptor Antagonists
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014