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)

NCT01618669 | Completed Phase 3 Results

• 1 other identifier: 3606-CL-3004
• Study Type: interventional
• Target: 1,147
• Locations: 4 countries
• Sites: 69

Brief 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.

Conditions

Coronary Artery Disease (CAD)

Keywords

Coronary Artery Disease (CAD); regadenoson; pharmacologic stress

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (11)

• Percentage of Participants With Treatment-emergent Clinically Significant Cardiac Events

  Within 1 hour for ECG events and up to 24 hours for adverse events after administration of regadenoson

• Proportion of Participants With Agreement in the Assessment of Absence or Presence of Ischemia Between First and Second Stress Scans

  Day 1 (stress MPI 1) and Day 2 -15 (stress MPI 2)

• Proportion of Participants With Agreement in the Assessment of Reversible Defects in 3 Categories of Ischemia Between First and Second Stress Scans

  Day 1 (stress MPI 1) and Day 2 - 15 (stress MPI 2)

• Proportion of Participants With Agreement in the Summed Stress Score (SSS) Between First and Second Stress Scans

  Day 1 (stress MPI 1) and Day 2 - 15 (stress MPI 2)

• Proportion of Participants With Agreement in the Summed Difference Score (SDS) Between First and Second Stress Scans

  Day 1 (rest MPI and stress MPI 1) and Day 2 - 15 (stress MPI 2)

Study Arms (2)

Regadenoson After Peak Exercise

EXPERIMENTAL

On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.

Drug: Regadenoson; Procedure: Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)

Regadenoson Alone

ACTIVE COMPARATOR

On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus (1 hour after exercise recovery), and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.

Drug: Regadenoson; Procedure: Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)

Interventions

Regadenoson DRUG

Administered as an intravenous (IV) bolus

Also known as: Lexiscan, CVT3146

Regadenoson After Peak Exercise; Regadenoson Alone

Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) PROCEDURE

Regadenoson After Peak Exercise; Regadenoson Alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (69)

Mobile Heart Specialists, PC

Mobile, Alabama, 36608, United States

Location

Silicon Valley Medical Imaging

Fremont, California, 94538, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

VA Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

Westside Medical Associates of Los Angeles

Los Angeles, California, 90211, United States

Location

Ventura Clinical Trials

Malibu, California, 90265, United States

Location

Mission Internal Medical Group

Mission Viejo, California, 92691, United States

Location

VA San Diego Healthcare System

San Diego, California, 92161, United States

Location

Santa Rosa Cardiology Medical Group, Inc.

Santa Rosa, California, 95405, United States

Location

Los Angeles Biomedical Research Institute

Torrance, California, 22908, United States

Location

HOCC - New Britain Campus

New Britain, Connecticut, 06050, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Alfieri Cardiology

Newark, Delaware, 19713, United States

Location

Delaware Clinical Trials

Wilmington, Delaware, 19808, United States

Location

Elite Research and Clinical Trials

Aventura, Florida, 33180, United States

Location

S & W Clinical Research

Fort Lauderdale, Florida, 33306, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Florida Heart Associates

Fort Myers, Florida, 33907, United States

Location

East Coast Institute for Research, LLC

Jacksonville, Florida, 32216, United States

Location

St. Luke's Cardiology St. Vincent's HealthCare

Jacksonville, Florida, 32216, United States

Location

Watson Medical Clinic/Lakeland Regional Medical Clinic

Lakeland, Florida, 33805, United States

Location

MIMA Century Research Associates

Melbourne, Florida, 32901, United States

Location

Cardiovascular Research Center of South Florida

Miami, Florida, 33173, United States

Location

Florida Hospital/Cardiovascular Institute

Orlando, Florida, 32803, United States

Location

University of South Florida

Tampa, Florida, 33620, United States

Location

Cardiology Partners Clinical Research Institute

Wellington, Florida, 33449, United States

Location

St. Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

University Cardiology Associates, LLC

Augusta, Georgia, 30901, United States

Location

South Coast Medical Group

Savannah, Georgia, 31406, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

I U School of Medicine/ Krannert Institute of Cardiology

Indianapolis, Indiana, 46202, United States

Location

Midwest Cardiology Associates

Overland Park, Kansas, 66209, United States

Location

Maine Research Associates

Portland, Maine, 04210, United States

Location

University of Maryland

Baltimore, Maryland, 21207, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Berkshire Medical Center

Pittsfield, Massachusetts, 01201, United States

Location

Henry Ford Hospital

Detriot, Michigan, 48202, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Michigan Heart

Ypsilanti, Michigan, 48197, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Cardiology Associates of North Mississippi

Tupelo, Mississippi, 38801, United States

Location

Cardiovascular Imaging Technologies

Kansas City, Missouri, 64111, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Alegent Health Heart and Vascular Specialists

Omaha, Nebraska, 68124, United States

Location

Alegent Health Research Center

Omaha, Nebraska, 68124, United States

Location

Las Vegas Radiology

Las Vegas, Nevada, 89113, United States

Location

Laurelton Medical center

Laurelton, New York, 11422, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Westchester Medical Center-New York Medical College

Valhalla, New York, 10595, United States

Location

Buffalo Cardiology & Pulmonary Associates, P.C.

Williamsville, New York, 14221, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Berks Cardiologists, Ltd.

Wyomissing, Pennsylvania, 19610, United States

Location

Katy Cardiology Associates

Katy, Texas, 77493, United States

Location

Mission Research Institute LLC

New Braunfels, Texas, 78130, United States

Location

West Houston Area Clinical Trial Consultants, LLC

Tomball, Texas, 77375, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Roanoke Heart Institute, PC

Roanoke, Virginia, 24014, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Hospital Italiano Garibaldi

Rosario, Santa Fe Province, S2000ODA, Argentina

Location

Instituto Oulton

Córdoba, X5000JJS, Argentina

Location

Instituto de Cardiologia la Plata

La Plata, B1925XAC, Argentina

Location

Hospital Italiano de La Plata

Provincia de Buenos Aires, B1900AX, Argentina

Location

Sanatorio San Geronimo

Santa Fe, S3001XAF, Argentina

Location

Clinica Anglo Americana

Lima, Lima 27, Peru

Location

Hospital Arzobispo Loayza

Lima, Peru

Location

Instituto Nacional Cardiovascular de EsSalud

Lima, Peru

Location

VA Caribbean Healthcare System (672)

San Juan, 00921, Puerto Rico

Location

Related Publications (1)

• Thomas GS, Cullom SJ, Kitt TM, Feaheny KM, Ananthasubramaniam K, Gropler RJ, Jain D, Thompson RC. The EXERRT trial: "EXErcise to Regadenoson in Recovery Trial": A phase 3b, open-label, parallel group, randomized, multicenter study to assess regadenoson administration following an inadequate exercise stress test as compared to regadenoson without exercise for myocardial perfusion imaging using a SPECT protocol. J Nucl Cardiol. 2017 Jun;24(3):788-802. doi: 10.1007/s12350-017-0813-3. Epub 2017 Feb 21.

  PMID: 28224449 DERIVED

Related Links

• Link to results on Astellas Clinical Study Results Web site

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

regadenoson

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Results Point of Contact

• Title: Senior Medical Director, Medical Affairs
• Organization: Astellas Pharma Global Development, Inc. (APGD)

Astellas.resultsdisclosure@astellas.com

Study Officials

• Senior Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2012
• First Posted: June 13, 2012
• Study Start: June 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 8, 2016
• Results First Posted: February 8, 2016

Record last verified: 2016-01

Locations

PE (3); US (60); AR (5); PR (1)