Trial Outcomes & Findings for An International Study to Evaluate Diagnostic Efficacy of Flurpiridaz (18F) Injection PET MPI in the Detection of Coronary Artery Disease (CAD) (NCT NCT03354273)

Last Updated: 2023-07-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

730 participants

Primary outcome timeframe

Up to 60 days

Results posted on

2023-07-12

Participant Flow

This study was conducted at 48 centers in Finland, France, Germany, Netherlands, United States and Canada from 05 June 2018 to 05 May 2022.

A total 730 participants signed informed consent and were enrolled, of these, 604 participants received greater than or equal to (\>=) 1 dose of Flurpiridaz (18F) Injection in this study.

Participant milestones

Participant milestones
Measure	Flurpiridaz (18F): All Participants Participants received 2 intravenous (IV) boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the invasive coronary angiography (ICA). Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 millicurie (mCi) (520 megabecquerel \[MBq\]) for an individual participant. Flurpiridaz was administered on Study Day 1. Single photon emission computed tomography (SPECT) agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection positron emission tomography (PET) myocardial perfusion imaging (MPI). Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Overall Study STARTED	730
Overall Study Safety Population (Treated)	604
Overall Study Modified Intent-to-Treat (MITT) Population	578
Overall Study Secondary Modified Intent-to-Treat (SMITT) Population	578
Overall Study COMPLETED	578
Overall Study NOT COMPLETED	152

Reasons for withdrawal

Reasons for withdrawal
Measure	Flurpiridaz (18F): All Participants Participants received 2 intravenous (IV) boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the invasive coronary angiography (ICA). Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 millicurie (mCi) (520 megabecquerel \[MBq\]) for an individual participant. Flurpiridaz was administered on Study Day 1. Single photon emission computed tomography (SPECT) agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection positron emission tomography (PET) myocardial perfusion imaging (MPI). Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Overall Study Adverse Event	5
Overall Study Screen Failure	21
Overall Study Withdrawal by Subject	34
Overall Study Technical Problems	30
Overall Study Lost to Follow-up	4
Overall Study Investigator Decision	3
Overall Study Investigational Medicinal Product (IMP) Supply Issues	21
Overall Study Issues With Performing Invasive Coronary Angiography (ICA)	20
Overall Study COVID-19 Restrictions	9
Overall Study Other	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Flurpiridaz (18F): All Participants n=730 Participants Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1. SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Age, Continuous	63.9 years STANDARD_DEVIATION 9.26 • n=5 Participants
Sex: Female, Male Female	235 Participants n=5 Participants
Sex: Female, Male Male	495 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	98 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	512 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	120 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	55 Participants n=5 Participants
Race (NIH/OMB) White	579 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	82 Participants n=5 Participants
Region of Enrollment Canada	129 Participants n=5 Participants
Region of Enrollment United States	412 Participants n=5 Participants
Region of Enrollment Finland	36 Participants n=5 Participants
Region of Enrollment France	71 Participants n=5 Participants
Region of Enrollment Germany	3 Participants n=5 Participants
Region of Enrollment Netherlands	79 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 60 days

Population: The MITT population included all participants who completed the rest and stress Flurpiridaz (18F) Injection PET MPI procedures and who had evaluable truth standard data. Here, "overall number of participants analyzed" signifies participants who were analyzed for a specific reader (combined sensitivity or specificity) and "number analyzed" signifies participants who were evaluable for specified categories.

Outcome measures

Outcome measures
Measure	Flurpiridaz (18F) n=578 Participants Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1. SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.	SPECT MPI SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
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 Reader 1: Sensitivity	77.1 percent Interval 71.9 to 82.3	—
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 Reader 1: Specificity	65.7 percent Interval 60.5 to 70.8	—
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 Reader 2: Sensitivity	73.5 percent Interval 68.0 to 79.0	—
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 Reader 2: Specificity	69.6 percent Interval 64.6 to 74.6	—
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 Reader 3: Sensitivity	88.8 percent Interval 84.8 to 92.7	—
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 Reader 3: Specificity	52.6 percent Interval 47.2 to 58.0	—
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 Majority Rule: Sensitivity	80.3 percent Interval 75.4 to 85.3	—
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 Majority Rule: Specificity	63.8 percent Interval 58.6 to 69.0	—

SECONDARY outcome

Timeframe: Up to 60 days

Population: The SMITT population included the participants who completed the rest and stress SPECT MPI (if the participant's SPECT MPI was "off-study," that SPECT MPI had to meet minimal quality standards, as specified by the imaging core lab). Here, "overall number of participants analyzed" signifies participants who were analyzed for a specific reader (combined sensitivity or specificity) and "number analyzed" signifies participants who were evaluable for specified categories.

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.

Outcome measures

Outcome measures
Measure	Flurpiridaz (18F) n=578 Participants Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1. SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.	SPECT MPI n=578 Participants SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
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 Reader 1: Sensitivity	77.1 percent Interval 71.9 to 82.3	62.7 percent Interval 56.6 to 68.7
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 Reader 1: Specificity	65.7 percent Interval 60.5 to 70.8	63.2 percent Interval 58.0 to 68.4
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 Reader 2: Sensitivity	73.5 percent Interval 68.0 to 79.0	60.6 percent Interval 54.6 to 66.7
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 Reader 2: Specificity	69.6 percent Interval 64.6 to 74.6	64.7 percent Interval 59.6 to 69.9
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 Reader 3: Sensitivity	88.8 percent Interval 84.8 to 92.7	75.5 percent Interval 70.2 to 80.8
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 Reader 3: Specificity	52.6 percent Interval 47.2 to 58.0	51.4 percent Interval 46.0 to 56.8
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 Majority Rule: Sensitivity	80.3 percent Interval 75.4 to 85.3	68.7 percent Interval 62.9 to 74.4
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 Majority Rule: Specificity	63.8 percent Interval 58.6 to 69.0	61.7 percent Interval 56.4 to 67.0

SECONDARY outcome

Timeframe: Up to 60 days

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.

Outcome measures

Outcome measures
Measure	Flurpiridaz (18F) n=188 Participants Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1. SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.	SPECT MPI n=188 Participants SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
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 Reader 1: Sensitivity	82.9 percent Interval 71.4 to 94.4	58.5 percent Interval 43.5 to 73.6
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 Reader 1: Specificity	72.8 percent Interval 65.6 to 80.0	63.3 percent Interval 55.5 to 71.1
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 Reader 2: Sensitivity	78.0 percent Interval 65.4 to 90.7	56.1 percent Interval 40.9 to 71.3
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 Reader 2: Specificity	75.5 percent Interval 68.6 to 82.5	68.7 percent Interval 61.2 to 76.2
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 Reader 3: Sensitivity	92.7 percent Interval 84.7 to 100.0	75.6 percent Interval 62.5 to 88.8
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 Reader 3: Specificity	59.2 percent Interval 51.2 to 67.1	58.5 percent Interval 50.5 to 66.5
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 Majority Rule: Sensitivity	82.9 percent Interval 71.4 to 94.4	65.9 percent Interval 51.3 to 80.4
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 Majority Rule: Specificity	72.8 percent Interval 65.6 to 80.0	66.0 percent Interval 58.3 to 73.6

SECONDARY outcome

Timeframe: Up to 60 days

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.

Outcome measures

Outcome measures
Measure	Flurpiridaz (18F) n=298 Participants Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1. SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.	SPECT MPI n=298 Participants SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
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 Reader 1: Sensitivity	72.6 percent Interval 64.6 to 80.7	60.7 percent Interval 51.8 to 69.5
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 Reader 1: Specificity	68.0 percent Interval 61.2 to 74.8	61.3 percent Interval 54.2 to 68.4
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 Reader 2: Sensitivity	70.1 percent Interval 61.8 to 78.4	63.2 percent Interval 54.5 to 72.0
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 Reader 2: Specificity	74.0 percent Interval 67.6 to 80.4	62.4 percent Interval 55.4 to 69.5
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 Reader 3: Sensitivity	88.0 percent Interval 82.2 to 93.9	74.4 percent Interval 66.4 to 82.3
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 Reader 3: Specificity	53.6 percent Interval 46.3 to 60.9	50.8 percent Interval 43.5 to 58.1
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 Majority Rule: Sensitivity	76.9 percent Interval 69.3 to 84.6	69.2 percent Interval 60.9 to 77.6
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 Majority Rule: Specificity	66.9 percent Interval 60.0 to 73.7	61.9 percent Interval 54.8 to 69.0

SECONDARY outcome

Timeframe: Up to 60 days

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.

Outcome measures

Outcome measures
Measure	Flurpiridaz (18F) n=194 Participants Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1. SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.	SPECT MPI n=194 Participants SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
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 Reader 1: Sensitivity	72.5 percent Interval 63.4 to 81.7	61.5 percent Interval 51.5 to 71.5
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 Reader 1: Specificity	60.2 percent Interval 50.7 to 69.6	56.3 percent Interval 46.7 to 65.9
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 Reader 2: Sensitivity	69.2 percent Interval 59.7 to 78.7	62.6 percent Interval 52.7 to 72.6
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 Reader 2: Specificity	69.9 percent Interval 61.0 to 78.8	58.3 percent Interval 48.7 to 67.8
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 Reader 3: Sensitivity	90.1 percent Interval 84.0 to 96.2	81.3 percent Interval 73.3 to 89.3
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 Reader 3: Specificity	47.6 percent Interval 37.9 to 57.2	39.8 percent Interval 30.4 to 49.3
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 Majority Rule: Sensitivity	75.8 percent Interval 67.0 to 84.6	71.4 percent Interval 62.1 to 80.7
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 Majority Rule: Specificity	61.2 percent Interval 51.8 to 70.6	51.5 percent Interval 41.8 to 61.1

Adverse Events

Flurpiridaz (18F): Safety Population

Serious events: 20 serious events

Other events: 145 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Flurpiridaz (18F): Safety Population n=604 participants at risk Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1. SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Cardiac disorders Acute myocardial infarction	0.33% 2/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Cardiac disorders Angina pectoris	0.33% 2/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Cardiac disorders Angina unstable	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Cardiac disorders Atrial fibrillation	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Cardiac disorders Bradycardia	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Cardiac disorders Coronary artery perforation	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Cardiac disorders Left ventricular dysfunction	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Cardiac disorders Ventricular fibrillation	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Cardiac disorders Ventricular tachycardia	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
General disorders Chest pain	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
General disorders Vascular stent thrombosis	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Immune system disorders Anaphylactic shock	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Injury, poisoning and procedural complications Post procedural fever	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Investigations Electrocardiogram abnormal	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Respiratory, thoracic and mediastinal disorders Asthma	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Skin and subcutaneous tissue disorders Urticaria chronic	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Vascular disorders Hypertensive crisis	0.17% 1/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.

Other adverse events

Other adverse events
Measure	Flurpiridaz (18F): Safety Population n=604 participants at risk Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1. SPECT agents 99mTc-based myocardial tracers, example \[99mTc\]tetrofosmin or \[99mTc\]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant. Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Cardiac disorders Angina pectoris	5.3% 32/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Nervous system disorders Headache	13.2% 80/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.3% 68/604 • From the time of informed consent to end of follow up (up to 77 days) The Safety population consisted of all enrolled participants who received \>=1 dose of Flurpiridaz (18F) Injection in the study.

Additional Information

Francois Tranquart, M.D., Ph.D

GE HealthCare

Phone: 447775543206

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI and/or institution is that the Sponsor can review results communications prior to public release and can restrict communications regarding trial results for a period that is more than 30 days (publications/abstracts) but not to exceed 90 days (patent related issues) from the time submitted to the Sponsor to review. The PI may be asked to remove any Sponsor confidential information and/or delay publication to protect any proprietary information.
Publication restrictions are in place

Restriction type: OTHER