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) - Full Text View

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:

MedlinePlus related topics: CT Scans Coronary Artery Disease Diagnostic Imaging Exercise and Physical Fitness

Drug Information available for: Regadenoson

U.S. FDA Resources

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
Study Completion Date:	December 2014
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

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: NCT01618669

Show 69 Study Locations

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:	December 22, 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 Coronary Disease Myocardial Ischemia Arterial Occlusive Diseases Arteriosclerosis Cardiovascular Diseases Heart Diseases Vascular Diseases Regadenoson	Adenosine A2 Receptor Agonists Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Pharmacologic Actions Physiological Effects of Drugs Purinergic Agents Purinergic Agonists Purinergic P1 Receptor Agonists

ClinicalTrials.gov processed this record on February 27, 2015

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)