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

Coronary Artery Disease (CAD) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03354273
• Other study ID #: GE-265-303
• Secondary ID: 2017-005011-14
• Status: Completed
• Phase: Phase 3
• Start date: June 5, 2018
• Est. completion date: May 5, 2022

Study information

• Verified date: June 2023
• Source: GE Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 730
• Est. completion date: May 5, 2022
• Est. primary completion date: May 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Canada	Center Hospitalier Universitaire de Sherbrooke CHUS	Montreal	Quebec
Canada	Montreal Heart Institute	Montréal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Finland	Turku University Hospital	Turku
France	Hopital Cote de Nacre	Caen
France	Groupe Hospitalier Bichat Claude Bernard	Paris
France	Centre Cardiologique Du Nord	Saint-Denis
Germany	Universitätsklinikum der RWTH Aachen	Aachen
Germany	Universitätsklinikum Essen	Essen
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	Amphia Ziekenhuis - WCN - PPDS	Breda
Netherlands	Catharina Hospital	Eindhoven
Netherlands	Zuyderland Medisch Centrum-WCN-PPDS	Heerlen
Netherlands	Leids Universitair Medisch Centrum	Leiden
Switzerland	Hopitaux Universitaires de Geneve	Geneva
Switzerland	Universitatsspital Zurich	Zürich
United States	Emory University	Atlanta	Georgia
United States	Vascular Biology and Hypertension Program, University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Virginia Health System	Charlottesville	Virginia
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	OhioHealth Research Institute	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	VA North Texas Health Care System - NAVREF - PPDS	Dallas	Texas
United States	University of Florida	Gainesville	Florida
United States	Indago Research and Health Center	Hialeah	Florida
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	Vital Heart & Vein	Humble	Texas
United States	University Of Iowa Hospitals And Clinics	Iowa City	Iowa
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Memorial City and Katy Cardiology Associates	Katy	Texas
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	Keck Hospital of USC	Los Angeles	California
United States	University of California- Los Angeles	Los Angeles	California
United States	VA Greater Los Angeles Health Care System	Los Angeles	California
United States	Allied Biomedical Research Institute	Miami	Florida
United States	Comprehensive Vascular Care PA	Miami	Florida
United States	Infinite Clinical Research	Miami	Florida
United States	Optimus U Corp	Miami	Florida
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Medical Center/New York Presbyterian Hospital - Milstein Hospital Building	New York	New York
United States	Cardiology Physicians PA/Red Clay Research LLC	Newark	Delaware
United States	Amavita Clinical Research, LLC	North Miami Beach	Florida
United States	Midwest Heart and Vascular Specialists	Overland Park	Kansas
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Roanoke Heart Institute	Roanoke	Virginia
United States	St Louis University	Saint Louis	Missouri
United States	VA St. Louis Health Care System	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	VA San Diego Health System	San Diego	California
United States	UCSF	San Francisco	California
United States	Tower Saint John's Imaging	Santa Monica	California
United States	Berks Cardiologists, LTD	Wyomissing	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
GE Healthcare	Pharmaceutical Product Development, LLC

Countries where clinical trial is conducted

United States,  Canada,  Finland,  France,  Germany,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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