An International Study to Evaluate Diagnostic Efficacy of Flurpiridaz (18F) Injection PET MPI in the Detection of Coronary Artery Disease (CAD)

A Phase 3, Open-Label, Multicentre Study of Flurpiridaz (18F) Injection for Positron Emission Tomography (PET) Imaging for Assessment of Myocardial Perfusion in Patients Referred for Invasive Coronary Angiography Because of Suspected Coronary Artery Disease

This is a Phase 3, prospective, open-label, international, multicentre study of Flurpiridaz (18F) Injection for PET MPI in patients referred for ICA because of suspected CAD.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease (CAD)
• Intervention / Treatment: Drug: PET MPI; Drug: SPECT MPI; Drug: Pharmacological stress agents

• Study Type: Interventional
• Enrollment (Actual): 730
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
  • Quebec
    • Montreal, Quebec, Canada, J1H 5N4
      • Center Hospitalier Universitaire de Sherbrooke CHUS
    • Montréal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
• Finland
  • Turku, Finland, FI-20520
    • Turku University Hospital
• France
  • Caen, France, 14033
    • Hopital Cote de Nacre
  • Paris, France, 75018
    • Groupe Hospitalier Bichat Claude Bernard
  • Saint-Denis, France, 93200
    • Centre Cardiologique du Nord
• Germany
  • Aachen, Germany, 52074
    • Universitatsklinikum der RWTH Aachen
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum
  • Breda, Netherlands, 4818 CK
    • Amphia Ziekenhuis - WCN - PPDS
  • Eindhoven, Netherlands, 5623 EJ
    • Catharina hospital
  • Heerlen, Netherlands, 6419 PC
    • Zuyderland Medisch Centrum-WCN-PPDS
  • Leiden, Netherlands, 2333ZA
    • Leids Universitair Medisch Centrum
• Switzerland
  • Geneva, Switzerland, 1205
    • Hôpitaux Universitaires de Genève
  • Zürich, Switzerland, 8091
    • Universitatsspital Zurich
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Vascular Biology and Hypertension Program, University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
    • Los Angeles, California, United States, 90024
      • University of California- Los Angeles
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Health Care System
    • San Diego, California, United States, 92161
      • VA San Diego Health System
    • San Francisco, California, United States, 94107
      • UCSF
    • Santa Monica, California, United States, 90403
      • Tower Saint John's Imaging
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • Delaware
    • Newark, Delaware, United States, 19713
      • Cardiology Physicians PA/Red Clay Research LLC
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center
    • Miami, Florida, United States, 33155
      • Allied Biomedical Research Institute
    • Miami, Florida, United States, 33125
      • Optimus U Corp
    • Miami, Florida, United States, 33133-4214
      • Infinite Clinical Research
    • Miami, Florida, United States, 33155
      • Comprehensive Vascular Care PA
    • North Miami Beach, Florida, United States, 33169
      • Amavita Clinical Research, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Midwest Heart and Vascular Specialists
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke'S Hospital of Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63106
      • VA St. Louis Health Care System
    • Saint Louis, Missouri, United States, 63110
      • St Louis University
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center/New York Presbyterian Hospital - Milstein Hospital Building
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Columbus, Ohio, United States, 43214
      • OhioHealth Research Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Berks Cardiologists, LTD
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75216
      • VA North Texas Health Care System - NAVREF - PPDS
    • Houston, Texas, United States, 77030
      • The Methodist Hospital Research Institute
    • Humble, Texas, United States, 77338
      • Vital Heart & Vein
    • Katy, Texas, United States, 77493
      • Memorial City and Katy Cardiology Associates
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
    • Roanoke, Virginia, United States, 24014
      • Roanoke Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The participant was a man or woman ≥18 years of age.
• The participant had read, signed, and dated an informed consent form (ICF) prior to any study procedures being performed.
• At the time of enrolment, the participant had been scheduled via written documentation to undergo an ICA for the assessment of CAD.
• The participant had undergone a clinically indicated SPECT OR the participant was willing to undergo SPECT MPI for the purposes of the clinical study.
• The participant was male or was a nonpregnant, nonlactating female who was either surgically sterile or was post-menopausal.
• The participant was able and willing to comply with all study procedures as described in the protocol.

Exclusion Criteria:

• Participants who were pregnant, may possibly be pregnant, or wish (including their partners) to became pregnant during the study period, or were lactating.
• Participants who were unable to undergo all of the imaging procedures.

• Participants who had an established diagnosis of CAD as confirmed by any of the following:

  1. Previous myocardial infarction (MI);
  2. Previous cardiac catheter angiography showing ≥50% stenosis;
  3. Previous coronary revascularisation, such as percutaneous coronary intervention (PCI), thrombolysis or coronary artery bypass graft (CABG) placement.
• Participants incapable of undergoing either exercise or pharmacological cardiac stress testing.
• Participants who had a current illness or pathology that, in the opinion of the investigator, would pose a significant safety risk for the participant during cardiac stress testing.
• Documented history of heart failure and/or cardiomyopathy and/or prior LV ejection fraction (LVEF) <50%).
• Participants scheduled for or planning to undergo any cardiac interventional procedures between enrolment and ICA.
• Participants undergoing evaluation for heart transplantation or with history of heart transplantation.
• Participants enrolled in another clinical study within the 30 days prior to being enrolled in this study or scheduled to participate in another clinical study during the 7-day follow-up period of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; Flurpiridaz PET MPI (following off-study SPECT MPI)

Drug: PET MPI; Flurpiridaz (18F) Injection. All participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest and 1 during stress. The dosages of Flurpiridaz (18F) Injection administered at rest and during stress conditions did not exceed a total of 14 mCi (520 MBq) for an individual participant.; Drug: SPECT MPI; SPECT imaging was used 99mTc-based myocardial tracers. SPECT agents utilised for the purposes of this clinical study was administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards, where applicable. All participants undergone SPECT MPI.; Drug: Pharmacological stress agents; Pharmacologic stress agents were restricted to the following 3 agents, as permitted by local marketing authorisations and availability: adenosine, dipyridamole, and regadenoson. Administration was through an IV line.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and Specificity of Flurpiridaz (18F) Injection Positron Emission Tomography (PET) Myocardial Perfusion Imaging (MPI) in the Detection of Significant Coronary Artery Disease (CAD) as Defined by Cardiac Catheterization	Sensitivity was defined as true positives (TP)/(TP+false negatives [FN]). TP was participants with abnormal PET MPI and disease positive by truth standard and FN was participants with normal PET MPI and disease positive by truth standard. Specificity defined as true negatives (TN)/(TN+ false positives [FP]). TN was participants with normal PET MPI and disease negative by truth standard and FP was participants with abnormal PET MPI and disease negative by truth standard. Truth standard was presence of CAD as evidenced by presence of stenosis of >=50 percent (%) in >=1 coronary artery or major branch of a coronary artery as determined by quantitative coronary angiography (QCA) analysis. Participants were considered to have CAD if QCA revealed >=50% stenosis of >=1 major coronary artery or major branch. Sensitivity and specificity were calculated for 3 readers and majority rule using each participant judgement (positive or negative) by at least 2 of 3 readers.	Up to 60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and Specificity of Flurpiridaz (18F) Injection PET MPI Compared SPECT MPI for All Participants When the Diagnosis of CAD by ICA Was the Standard of Truth	Sensitivity:TP/(TP+FN). TP:participants with abnormal PET MPI and disease positive by truth standard and FN:participants with normal PET MPI and disease positive by truth standard. Specificity:TN/(TN+ FP). TN:participants with normal PET MPI and disease negative by truth standard and FP:participants with abnormal PET MPI and disease negative by truth standard. Truth standard was presence of CAD as evidenced by presence of stenosis of >=50% in >=1 coronary artery or major branch of coronary artery as determined by QCA analysis. Participants considered to have CAD if QCA revealed >=50% stenosis of >=1 major coronary artery or major branch. Sensitivity, specificity was calculated for 3 readers and majority rule using each participant judgement (positive or negative) by at least 2 of 3 readers. Sensitivity, specificity of Flurpiridaz (18F) PET MPI compared to SPECT MPI with QCA as standard of truth at >=50% stenosis threshold for all participants was reported by reader and majority rule.	Up to 60 days
Sensitivity and Specificity of Flurpiridaz (18F) Injection PET MPI Compared SPECT MPI for Female Participants When the Diagnosis of CAD by ICA Was the Standard of Truth	Sensitivity:TP/(TP+FN). TP:participants with abnormal PET MPI and disease positive by truth standard and FN:participants with normal PET MPI and disease positive by truth standard. Specificity:TN/(TN+ FP). TN:participants with normal PET MPI and disease negative by truth standard and FP:participants with abnormal PET MPI and disease negative by truth standard. Truth standard was presence of CAD as evidenced by presence of stenosis of >=50% in >=1 coronary artery or major branch of a coronary artery as determined by QCA analysis. Participants considered to have CAD if QCA revealed >=50% stenosis of >=1 major coronary artery or major branch. Sensitivity, specificity calculated for 3 readers and majority rule using each participant judgement (positive or negative) by at least 2 of 3 readers. Sensitivity, specificity of Flurpiridaz (18F) PET MPI compared to SPECT MPI with QCA as standard of truth at >=50% stenosis threshold for female participants was reported by reader and majority rule.	Up to 60 days
Sensitivity and Specificity of Flurpiridaz (18F) Injection PET MPI Compared SPECT MPI for Participants With Body-mass Index (BMI) >=30 Kilograms Per Square Meter (kg/m^2) When the Diagnosis of CAD by ICA Was the Standard of Truth	Sensitivity:TP/(TP+FN). TP:participants with abnormal PET MPI and disease positive by truth standard and FN:participants with normal PET MPI and disease positive by truth standard. Specificity:TN/(TN+ FP). TN:participants with normal PET MPI and disease negative by truth standard and FP:participants with abnormal PET MPI and disease negative by truth standard. Truth standard was presence of CAD as evidenced by presence of stenosis of >=50% in >=1 coronary artery or major branch of coronary artery determined by QCA analysis. Participants considered to have CAD if QCA revealed >=50% stenosis of >=1 major coronary artery or major branch. Sensitivity, specificity calculated for 3 readers and majority rule using each participant judgement (positive or negative) by at least 2 of 3 readers. Sensitivity, specificity of Flurpiridaz (18F) PET MPI compared to SPECT MPI with QCA as standard of truth at >=50% stenosis threshold for participants(BMI>=30 kg/m^2) reported by reader and majority rule.	Up to 60 days
Sensitivity and Specificity of Flurpiridaz (18F) Injection PET MPI Compared SPECT MPI for Diabetic Participants When the Diagnosis of CAD by ICA Was the Standard of Truth	Sensitivity:TP/(TP+FN). TP:participants with abnormal PET MPI and disease positive by truth standard and FN:participants with normal PET MPI and disease positive by truth standard. Specificity:TN/(TN+ FP). TN:participants with normal PET MPI and disease negative by truth standard and FP:participants with abnormal PET MPI and disease negative by truth standard. Truth standard was presence of CAD as evidenced by presence of stenosis of >=50% in >=1 coronary artery or major branch of coronary artery determined by QCA analysis. Participants considered to have CAD if QCA revealed >=50% stenosis of >=1 major coronary artery or major branch. Sensitivity and specificity calculated for 3 readers and majority rule using each participant judgement (positive or negative) by at least 2 of 3 readers. Sensitivity, specificity of Flurpiridaz (18F) PET MPI compared to SPECT MPI with QCA as standard of truth at >=50% stenosis threshold for diabetic participants was reported by reader and majority rule.	Up to 60 days

Collaborators and Investigators

• Sponsor: GE Healthcare
• Collaborators: Pharmaceutical Product Development, LLC
• Investigators: Study Director: Francois Tranquart, M.D., Ph.D., General Electric Healthcare Life Sciences

Publications and helpful links

General Publications

• Bourque JM, Hanson CA, Agostini D, Bateman TM, Bax JJ, Beanlands RSB, Berman DS, Garcia EV, Heller GV, Knuuti J, Tamaki N, Udelson JE, Maddahi J. Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging. J Nucl Cardiol. 2021 Jun;28(3):1105-1116. doi: 10.1007/s12350-021-02527-8. Epub 2021 Jan 31.

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2018
• Primary Completion (Actual): May 5, 2022
• Study Completion (Actual): May 5, 2022

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: November 21, 2017
• First Posted (Actual): November 27, 2017

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: June 19, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Coronary artery disease (CAD); Positron emission tomography myocardial perfusion imaging (PET MPI); Single photon emission computed tomography myocardial perfusion imaging (SPECT MPI); Invasive coronary angiography (ICA)
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: GE-265-303; 2017-005011-14 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No