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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Coronary Artery Disease (CAD)

Intervention / Treatment
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* Drug: PET MPI
* Drug: SPECT MPI
* Drug: Pharmacological stress agents


Participation Criteria
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Eligibility Criteria
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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: Previous myocardial infarction (MI); Previous cardiac catheter angiography showing ≥50% stenosis; 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Flurpiridaz PET MPI (following off-study SPECT MPI) | Drug: PET MPI<br>* 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.<br>Drug: SPECT MPI<br>* 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.<br>Drug: Pharmacological stress agents<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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)