Coronary Artery Disease (CAD)
Conditions
Keywords
Positron emission tomography myocardial perfusion imaging (PET MPI), Single photon emission computed tomography myocardial perfusion imaging (SPECT MPI), Invasive coronary angiography (ICA), Coronary artery disease (CAD)
Brief 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.
Interventions
DRUGPET 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.
DRUGSPECT 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.
DRUGPharmacological 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.
Sponsors
Pharmaceutical Product Development, (PPD) LLC
GE Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to 60 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
Countries
Canada, Finland, France, Germany, Netherlands, Switzerland, United States
Participant flow
Recruitment details
This study was conducted at 48 centers in Finland, France, Germany, Netherlands, United States and Canada from 05 June 2018 to 05 May 2022.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Flurpiridaz (18F): All 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. | 730 |
| Total | 730 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | COVID-19 Restrictions | 9 |
| Overall Study | Investigational Medicinal Product (IMP) Supply Issues | 21 |
| Overall Study | Investigator Decision | 3 |
| Overall Study | Issues With Performing Invasive Coronary Angiography (ICA) | 20 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Other | 5 |
| Overall Study | Screen Failure | 21 |
| Overall Study | Technical Problems | 30 |
| Overall Study | Withdrawal by Subject | 34 |
Baseline characteristics
| Characteristic | Flurpiridaz (18F): All Participants |
|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 9.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 98 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 512 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 120 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 55 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 82 Participants |
| Race (NIH/OMB) White | 579 Participants |
| Region of Enrollment Canada | 129 Participants |
| Region of Enrollment Finland | 36 Participants |
| Region of Enrollment France | 71 Participants |
| Region of Enrollment Germany | 3 Participants |
| Region of Enrollment Netherlands | 79 Participants |
| Region of Enrollment United States | 412 Participants |
| Sex: Female, Male Female | 235 Participants |
| Sex: Female, Male Male | 495 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 604 |
| other Total, other adverse events | 145 / 604 |
| serious Total, serious adverse events | 20 / 604 |
Outcome results
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
Comparison: Reader 1: Sensitivityp-value: <0.0001One-sided z-tests
Comparison: Reader 1: Specificityp-value: 0.0182One-sided z-tests
Comparison: Reader 2: Sensitivityp-value: <0.0001One-sided z-tests
Comparison: Reader 2: Specificityp-value: 0.0002One-sided z-tests
Comparison: Reader 3: Sensitivityp-value: <0.0001One-sided z-tests
Comparison: Reader 3: Specificityp-value: 0.997One-sided z-tests
Comparison: Majority Rule: Sensitivityp-value: <0.0001One-sided z-tests
Comparison: Majority Rule: Specificityp-value: 0.0781One-sided z-tests
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| SPECT MPI | 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 | 61.7 percent |
| SPECT MPI | 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 | 75.5 percent |
| SPECT MPI | 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 | 62.7 percent |
| SPECT MPI | 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 | 68.7 percent |
| SPECT MPI | 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 | 63.2 percent |
| SPECT MPI | 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 | 51.4 percent |
| SPECT MPI | 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 | 60.6 percent |
| SPECT MPI | 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 | 64.7 percent |
Comparison: Reader 1: Sensitivityp-value: <0.000195% CI: [6.5, 22.4]McNemar
Comparison: Reader 1: Specificityp-value: 0.000495% CI: [-4.9, 9.7]Nam's RMLE
Comparison: Reader 2: Sensitivityp-value: 0.000295% CI: [4.7, 21]McNemar
Comparison: Reader 2: Specificityp-value: <0.000195% CI: [-2.1, 11.8]Nam's RMLE
Comparison: Reader 3: Sensitivityp-value: <0.000195% CI: [6.6, 19.9]McNemar
Comparison: Reader 3: Specificityp-value: 0.001195% CI: [-6, 8.4]Nam's RMLE
Comparison: Majority Rule: Sensitivityp-value: 0.000395% CI: [4.1, 19.2]McNemar
Comparison: Majority Rule: Specificityp-value: 0.000495% CI: [-5, 9.3]Nam's RMLE
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| SPECT MPI | 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 | 51.5 percent |
| SPECT MPI | 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 | 61.5 percent |
| SPECT MPI | 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 | 81.3 percent |
| SPECT MPI | 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 | 56.3 percent |
| SPECT MPI | 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 | 71.4 percent |
| SPECT MPI | 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 | 62.6 percent |
| SPECT MPI | 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 | 39.8 percent |
| SPECT MPI | 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 | 58.3 percent |
Comparison: Reader 1: Sensitivityp-value: 0.029495% CI: [-2.6, 24.6]McNemar
Comparison: Reader 1: Specificityp-value: 0.011795% CI: [-8.3, 16.1]Nam's RMLE
Comparison: Reader 2: Sensitivityp-value: 0.144495% CI: [-7.1, 20.3]McNemar
Comparison: Reader 2: Specificityp-value: 0.000195% CI: [-0.4, 23.7]Nam's RMLE
Comparison: Reader 3: Sensitivityp-value: 0.04495% CI: [-1.3, 18.9]McNemar
Comparison: Reader 3: Specificityp-value: 0.002295% CI: [-4.8, 20.3]Nam's RMLE
Comparison: Majority Rule: Sensitivityp-value: 0.216495% CI: [-8.4, 17.2]McNemar
Comparison: Majority Rule: Specificityp-value: 0.000695% CI: [-2.6, 22]Nam's RMLE
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| SPECT MPI | 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 | 66.0 percent |
| SPECT MPI | 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 | 58.5 percent |
| SPECT MPI | 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 | 75.6 percent |
| SPECT MPI | 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 | 63.3 percent |
| SPECT MPI | 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 | 65.9 percent |
| SPECT MPI | 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 | 56.1 percent |
| SPECT MPI | 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 | 58.5 percent |
| SPECT MPI | 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 | 68.7 percent |
Comparison: Reader 1: Sensitivityp-value: 0.012795% CI: [5.4, 43.4]McNemar
Comparison: Reader 1: Specificityp-value: 0.000195% CI: [-1.2, 20.2]Nam's RMLE
Comparison: Reader 2: Sensitivityp-value: 0.019595% CI: [2.2, 41.7]McNemar
Comparison: Reader 2: Specificityp-value: 0.000495% CI: [-3.2, 16.8]Nam's RMLE
Comparison: Reader 3: Sensitivityp-value: 0.017495% CI: [1.7, 32.4]McNemar
p-value: 0.02495% CI: [-9.9, 11.3]Nam's RMLE
Comparison: Majority Rule: Sensitivityp-value: 0.044895% CI: [-1.5, 35.6]McNemar
Comparison: Majority Rule: Specificityp-value: 0.000495% CI: [-3.4, 17]Nam's RMLE
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| Flurpiridaz (18F) | 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 |
| SPECT MPI | 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 | 61.9 percent |
| SPECT MPI | 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 | 60.7 percent |
| SPECT MPI | 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 | 74.4 percent |
| SPECT MPI | 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 | 61.3 percent |
| SPECT MPI | 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 | 69.2 percent |
| SPECT MPI | 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 | 63.2 percent |
| SPECT MPI | 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 | 50.8 percent |
| SPECT MPI | 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 | 62.4 percent |
Comparison: Reader 1: Sensitivityp-value: 0.011695% CI: [0, 23.9]McNemar
Comparison: Reader 1: Specificityp-value: 0.000395% CI: [-2.9, 16.2]Nam's RMLE
Comparison: Reader 2: Sensitivityp-value: 0.108595% CI: [-5.2, 18.9]McNemar
Comparison: Reader 2: Specificityp-value: <0.000195% CI: [2.1, 21.1]Nam's RMLE
Comparison: Reader 3: Sensitivityp-value: 0.001795% CI: [3.8, 23.5]McNemar
Comparison: Reader 3: Specificityp-value: 0.003495% CI: [-6.6, 12.1]Nam's RMLE
Comparison: Majority Rule: Sensitivityp-value: 0.064195% CI: [-3.6, 19]McNemar
Comparison: Majority Rule: Specificityp-value: 0.00195% CI: [-4.6, 14.6]Nam's RMLE