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)

Coronary Artery Disease (CAD) Clinical Trial

— EXERRT  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01618669
• Other study ID #: 3606-CL-3004
• Status: Completed
• Phase: Phase 3
• First received: May 29, 2012
• Last updated: January 7, 2016
• Start date: June 2012
• Est. completion date: December 2014

Study information

• Verified date: January 2016
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaPeru: Instituto Nacional de SaludPeru: General Directorate of Pharmaceuticals, Devices, and Drugs
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1147
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Artery Disease (CAD)
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Regadenoson
Administered as an intravenous (IV) bolus

Procedure:
• Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)

Locations

Country	Name	City	State
Argentina	Instituto Oulton	Cordoba
Argentina	Instituto de Cardiologia la Plata	La Plata
Argentina	Hospital Italiano de La Plata	Provincia de Buenos Aires
Argentina	Hospital Italiano Garibaldi	Rosario	Santa Fé
Argentina	Sanatorio San Geronimo	Santa Fe
Peru	Clinica Anglo Americana	Lima
Peru	Hospital Arzobispo Loayza	Lima
Peru	Instituto Nacional Cardiovascular de EsSalud	Lima
Puerto Rico	VA Caribbean Healthcare System (672)	San Juan
United States	St. Joseph's Hospital	Atlanta	Georgia
United States	University Cardiology Associates, LLC	Augusta	Georgia
United States	Elite Research and Clinical Trials	Aventura	Florida
United States	University of Maryland	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	Henry Ford Hospital	Detriot	Michigan
United States	Wayne State University	Detroit	Michigan
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	S & W Clinical Research	Fort Lauderdale	Florida
United States	Florida Heart Associates	Fort Myers	Florida
United States	Silicon Valley Medical Imaging	Fremont	California
United States	I U School of Medicine/ Krannert Institute of Cardiology	Indianapolis	Indiana
United States	East Coast Institute for Research, LLC	Jacksonville	Florida
United States	St. Luke's Cardiology St. Vincent's HealthCare	Jacksonville	Florida
United States	Cardiovascular Imaging Technologies	Kansas City	Missouri
United States	Katy Cardiology Associates	Katy	Texas
United States	Watson Medical Clinic/Lakeland Regional Medical Clinic	Lakeland	Florida
United States	Las Vegas Radiology	Las Vegas	Nevada
United States	Laurelton Medical center	Laurelton	New York
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	VA Greater Los Angeles Healthcare System	Los Angeles	California
United States	Westside Medical Associates of Los Angeles	Los Angeles	California
United States	Ventura Clinical Trials	Malibu	California
United States	MIMA Century Research Associates	Melbourne	Florida
United States	Cardiovascular Research Center of South Florida	Miami	Florida
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Mission Internal Medical Group	Mission Viejo	California
United States	Mobile Heart Specialists, PC	Mobile	Alabama
United States	Mission Research Institute LLC	New Braunfels	Texas
United States	HOCC - New Britain Campus	New Britain	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Alfieri Cardiology	Newark	Delaware
United States	Alegent Health Heart and Vascular Specialists	Omaha	Nebraska
United States	Alegent Health Research Center	Omaha	Nebraska
United States	Florida Hospital/Cardiovascular Institute	Orlando	Florida
United States	Midwest Cardiology Associates	Overland Park	Kansas
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Berkshire Medical Center	Pittsfield	Massachusetts
United States	Maine Research Associates	Portland	Maine
United States	Roanoke Heart Institute, PC	Roanoke	Virginia
United States	VA San Diego Healthcare System	San Diego	California
United States	Santa Rosa Cardiology Medical Group, Inc.	Santa Rosa	California
United States	South Coast Medical Group	Savannah	Georgia
United States	University of Washington	Seattle	Washington
United States	Washington University School of Medicine	St. Louis	Missouri
United States	University of South Florida	Tampa	Florida
United States	West Houston Area Clinical Trial Consultants, LLC	Tomball	Texas
United States	Los Angeles Biomedical Research Institute	Torrance	California
United States	Cardiology Associates of North Mississippi	Tupelo	Mississippi
United States	Westchester Medical Center-New York Medical College	Valhalla	New York
United States	Cardiology Partners Clinical Research Institute	Wellington	Florida
United States	Buffalo Cardiology & Pulmonary Associates, P.C.	Williamsville	New York
United States	Delaware Clinical Trials	Wilmington	Delaware
United States	Berks Cardiologists, Ltd.	Wyomissing	Pennsylvania
United States	Michigan Heart	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Peru,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants With Majority Reader Self-agreement in Ischemia Assessment Between First and Second Stress Scans	SPECT scans were reviewed in a blinded fashion by 3 independent expert readers using the 17-segment model for standardized myocardial segmentation. At rest and stress, each segment was scored on a 0 (normal) to 4 (absent contrast/radiotracer uptake) scale by each of the 3 blinded readers according to the amount of contrast or radiotracer the myocardium in the segment absorbed. 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.; The number of segments with reversible defects was categorized as absence (0 - 1 reversible segments) or presence (= 2 defects reversible segments) of ischemia.; Each reader was defined as having self-agreement based upon identical categorization of a given participant as absent or present for ischemia for both the initial and second stress visits.; Majority agreement is if at least 2 out of the 3 blinded readers demonstrated self-agreement for a given participant.	Day 1 (rest scan and first stress scan) and Day 2 -15 (second stress scan)	No
Secondary	Percentage of Participants With Treatment-emergent Clinically Significant Cardiac Events	A clinically significant cardiac event is defined as: Any of the following events found on the Holter electrocardiogram (ECG)/12-Lead ECG within 1 hour after regadenoson administration: ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes, ventricular flutter),; ST-T depression (> 2 mm),; ST-T elevation (=1 mm),; Atrioventricular (AV) block (2:1 AV block, AV Mobitz I, AV Mobitz II, complete heart block); sinus arrest > 3 seconds in duration; Or; a treatment-emergent adverse event (TEAE) per the Medical Dictionary for Regulatory Activities (MedDRA) Standardised MedDRA Queries (SMQ) (Narrow Scope) for myocardial infarction; Or; a TEAE preferred term of angina unstable within 24 hours of regadenoson administration.	Within 1 hour for ECG events and up to 24 hours for adverse events after administration of regadenoson	Yes
Secondary	Proportion of Participants With Agreement in the Assessment of Absence or Presence of Ischemia Between First and Second Stress Scans	The number of segments with reversible defects was assessed by each of the 3 blinded independent expert readers. Based on the median count of the number of reversible defects across the 3 readers, categorized as absence (0 to 1 reversible segments) or presence (= 2 reversible defects) of ischemia, the proportion of participants with agreement in the presence and absence of ischemia between the first and second stress scans was calculated.	Day 1 (stress MPI 1) and Day 2 -15 (stress MPI 2)	No
Secondary	Proportion of Participants With Agreement in the Assessment of Reversible Defects in 3 Categories of Ischemia Between First and Second Stress Scans	The number of segments with reversible defects was assessed by each of the 3 blinded independent expert readers. Based on the median count of the number of reversible defects across the 3 readers, categorized as 0 to 1, 2 to 4, or = 5 reversible segments, the proportion of participants with agreement in the three ischemia categories between the first and second stress scans was to be calculated. In the reported data, these proportions only include the 0-1 and 2-4 categories; the = 5 category was not included because there were no participants in this category for the Regadenoson Alone group for the initial stress MPI.	Day 1 (stress MPI 1) and Day 2 - 15 (stress MPI 2)	No
Secondary	Proportion of Participants With Agreement in the Summed Stress Score (SSS) Between First and Second Stress Scans	The 17-segment model for standardized myocardial segmentation was used to analyze MPI scans. 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 Summed Stress Score (SSS) was calculated as the sum of the stress scores across the 17 segments. The mean value (rounded to the nearest integer) across the 3 readers was computed and the SSS was categorized into 4 group categorical variables based on the score: 0 to 3, 4 to 7, 8 to 11, and = 12. The proportion of participants with agreement in respect to these categories between the two stress scans was calculated.	Day 1 (stress MPI 1) and Day 2 - 15 (stress MPI 2)	No
Secondary	Proportion of Participants With Agreement in the Summed Difference Score (SDS) Between First and Second Stress Scans	The 17-segment model for standardized myocardial segmentation was used to analyze MPI scans. 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/ uptake; 2: moderately reduced contrast/uptake; 3: severely reduced contrast/uptake; 4: absent contrast/uptake.; SSS was calculated as the sum of the stress scores across the 17 segments and the Summed Rest Score (SRS) was calculated as the sum of the rest scores across the 17 segments. The Summed Difference Score (SDS) is the difference in the SSS and SRS (SSS - SRS).; The mean value (rounded to the nearest integer) across the 3 readers was computed and the SDS was categorized into 3 categorical variables based on the score: 0 to 6, 7 to 13 and = 14. The proportion of participants with agreement in respect to these categories between the two stress scans was calculated.	Day 1 (rest MPI and stress MPI 1) and Day 2 - 15 (stress MPI 2)	No
Secondary	Participants With Less, the Same, or More Reversible Perfusion Defects Shown by the First Stress Scan When Compared to the Second Stress Scan	Each reader evaluated the initial stress SPECT MPI scan compared to the participant's second stress SPECT MPI scan (blinded at time of the evaluation) for whether there was Less (-1), the Same (0) or More (1) reversible perfusion defects. The median assessment of the 3 blinded readers was used to summarize the number of participants in each category.	Day 1 (stress MPI 1) and Day 2-15 (stress MPI 2)	No
Secondary	Overall Assessment of Image Quality	The image quality for each scan was rated by each independent reader as 1 = Poor, 2 = Fair, 3 = Good, 4 = Excellent. Based on the median rating of overall image quality across the three readers, the number of participants with each rating is reported for each scan.	Day 1 (rest MPI and stress MPI 1) and Day 2 - 15 (stress MPI 2)	No
Secondary	Target to Background Radiotracer Uptake Ratios From the First and Second Stress Scans	Image quality was assessed through radiotracer uptake in the heart (target organ) compared to liver, gut and combined liver plus gut (background interference).	Day 1 (stress MPI 1) and Day 2 - 15 (stress MPI 2)	No
Secondary	Percentage of Scans With Subdiaphragmatic Interference	Each reader assessed the sub-diaphragmatic radiotracer interference with cardiac image quality using a 4-point scale of 0 = none, 1 = slight, 2 = moderate or 3 = severe for each stress SPECT MPI. The median rating across the 3 readers was used to summarize the percentage of scans with interference.	Day 1 (stress MPI 1) and Day 2 -15 (stress MPI 2)	No
Secondary	Percentage of Cardiac Segments Obscured by Subdiaphragmatic Activity	The number of cardiac segments obscured by the sub-diaphragmatic activity by group by stress SPECT MPI scan and by reader is reported.	Day 1 (stress MPI 1) and Day - 15 (stress MPI 2)	No
Secondary	Number of Participants With Adverse Events Within 24 Hours After Administration of Regadenoson	An adverse event is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: Results in death,; Is life threatening,; Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions,; Results in congenital anomaly, or birth defect,; Requires inpatient hospitalization or leads to prolongation of hospitalization; Other medically important events.; Relationship to study drug was assessed by the investigator.	Up to 24 hours after study drug administration for each stress MPI (Day 1 and Day 2-15)	Yes

External Links

•   Link to results on Astellas Clinical Study Results Web site