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: June 17, 2014
Last verified: June 2014

May 29, 2012
June 17, 2014
June 2012
December 2014   (final data collection date for primary outcome measure)
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.
Median count of the number of segments with reversible defects categorized as absence (0-1) or presence of ischemia (≥2) [ Time Frame: Visit 2 (Day 1) and Visit 3 (Day 2 up to Day 15) ] [ Designated as safety issue: No ]
Non-inferiority will be provided by a confidence interval on the difference in agreement rates (agreement rate for SPECT images at Visit 2 and Visit 3 in Regadenoson After Peak Exercise arm minus agreement rate for SPECT images at Visit 2 and Visit 3 in Regadenoson Alone arm). Measure of agreement is average rate of agreement for absence or presence of ischemia based on median count between the successive scan images. The median count is across three blinded independent expert readers.
Complete list of historical versions of study NCT01618669 on ClinicalTrials.gov Archive Site
  • 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
  • Agreement rates between SPECT imaging with regadenoson following inadequate exercise stress testing and SPECT imaging with regadenoson alone using 3 categories for ischemia [ Time Frame: Visit 2 (Day 1) and Visit 3 (Day 2 up to Day 15) ] [ Designated as safety issue: No ]
    Ischemia categories are 0-1, 2-4, ≥ 5 reversible segments
  • 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 ]
    Image pairs include regadenoson following inadequate exercise versus regadenoson and regadenoson versus regadenoson
  • 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 0-4 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 scores are defined as: 0=normal radiotracer uptake, 1=slightly reduced radiotracer uptake, 2=moderately reduced radiotracer uptake, 3=severely reduced radiotracer uptake and 4=absent radiotracer uptake
  • 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 ]
  • Percentage of subjects who experience one or more clinically significant cardiac events found on electrocardiogram (ECG) [ Time Frame: within 1 hour 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 and/or percentage of subjects experiencing adverse events of acute coronary syndrom (unstable angina and/or acute myocardial infarction)
  • 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
Not Provided
Not Provided
 
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)
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)

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Coronary Artery Disease (CAD)
Drug: Regadenoson
Intravenous (IV)
Other Name: Lexiscan, CVT3146
  • Experimental: Regadenoson After Peak Exercise
    Intervention: Drug: Regadenoson
  • Active Comparator: Regadenoson Alone
    Intervention: Drug: Regadenoson
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
1147
December 2014
December 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Peru,   Puerto Rico
 
NCT01618669
3606-CL-3004
No
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Astellas Pharma Global Development, Inc.
Not Provided
Study Director: Senior Medical Director Astellas Pharma Global Development, Inc.
Astellas Pharma Inc
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP