A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients With CAD.

The study will assess the diagnostic efficacy (sensitivity and specificity) of Flurpiridaz F18 Injection MPI against SPECT MPI in patients screened for CAD as determined by ICA. Six hundred and eighty evaluable patients will be enrolled and will undergo SPECT MPI and Flurpiridaz F18 PET MPI. Patients will be considered for enrollment if they are scheduled to undergo or have undergone prior ICA without intervention (being either positive or negative for CAD).

• Flurpiridaz F18 (Drug), also known as flurpiridaz F 18: Injection of Flurpiridaz F18 for the purposes of PET myocardial profusion imaging (MPI) analysis
• 99mTechnicium (sestamibi or tetrofosmin) (Drug), also known as 99mTc sestamibi or 99mTc Tetrofosmin: Injection of 99mTc sestamibi or tetrofosmin for the purposes of SPECT MPI analysis

Primary outcomes

• Diagnostic Efficacy of Flurpiridaz F 18 PET Myocardial Perfusion Imaging (MPI) Sensitivity Versus SPECT Myocardial Perfusion Imaging Sensitivity [60 days]: Diagnostic efficacy of one day rest and stress flurpiridaz F 18 PET MPI sensitivity versus SPECT MPI sensitivity in the detection of coronary artery disease (CAD) by majority rule using invasive coronary angiography as the truth standard,
• Diagnostic Efficacy of Flurpiridaz PET MPI Specificity Versus SPECT MPI Specificity [60 days]: Diagnostic efficacy of flurpiridaz PET MPI specificity versus SPECT MPI specificity by majority rule in the detection of CAD using invasive coronary angiography as the truth standard

Secondary outcomes

• Diagnostic Efficacy of Flurpiridaz F18 PET MPI Sensitivity Versus SPECT MPI Sensitivity in Subgroups: Pharmacologic Stress, Females and BMI>/=30. [60 days]: Diagnostic efficacy of flurpiridaz F18 PET MPI sensitivity versus SPECT MPI sensitivity by majority rule in the detection of CAD using invasive coronary angiography as the truth standard, , in subgroups: pharmacologic stress, females and BMI >/=30. Value reported is the number of true positives, i.e. True Positive: Patients with abnormal MPI and disease positive by the truth standard I
• Diagnostic Efficacy of Flurpiridaz F18 PET MPI Specificity Versus SPECT Specificity in Subgroups: Pharmacologic Stress, Females and BMI>/=30. [60 days]: Diagnostic efficacy of flurpiridaz F18 PET MPI specificity versus SPECT specificity by majority rule in the detection of CAD using invasive coronary angiography as the truth standard, in subgroups: pharmacologic stress, females and BMI >/=30. Value represents the number of true negative, i.e. True Negative: Patients with normal MPI and disease negative by the truth standard
• Diagnostic Performance Evaluation of Localization of CAD for Sensitivity (PETVsSPECT). [60 days]: Overall sensitivity of flurpiridaz F18 PET MPI in coronary territories (Qualitative Diagnosis vs. SPECT MPI by majority rule vs. truth standard (angiographic stenosis greater than or equal to 50% stenosis and confirmed MI); left descending coronary artery (LAD), left circumflex artery (LCX), right coronary artery (RCA), and non - LAD. Value reported is the number of true positives, i.e. True Positive: Patients with abnormal MPI and disease positive by the truth standard
• Diagnostic Performance Evaluation of Localization of CAD for Specificity (PETVsSPECT). [60 days]: Overall specificity of flurpiridaz F18 PET MPI in Coronary Territories (Qualitative Diagnosis) vs. SPECT MPI by majority rule vs. truth standard (angiographic stenosis greater than or equal to 50% stenosis and confirmed MI); left descending coronary artery (LAD), left circumflex artery (LCX), right coronary artery (RCA), and non - LAD. Value represents the number of true negative, i.e. True Negative: Patients with normal MPI and disease negative by the truth standard
• Diagnositic Performance Evaluation of Multivessel Disease (PETvsSPECT). [60 days]: Overall summary of sensitivity for identifying multi-vessel disease between flurpiridaz F18 PET MPI and SPECT MPI by majority rule vs. truth standard (angio >/=50% stenosis and confirmed MI). Value reported is the number of true positives, i.e. True Positive: Patients with abnormal MPI and disease positive by the truth standard
• Diagnositic Performance Evaluation of Multivessel Disease (PETvsSPECT). [60 days]: Overall summary of specificity for identifying multi-vessel disease between flurpiridaz F18 PET MPI and SPECT MPI by majority rule vs. majority rule (angio >/=50% stenosis and confirmed MI). Value represents the number of true negative, i.e. True Negative: Patients with normal MPI and disease negative by the truth standard
• Overall Summary of Sensitivity of PET MPI vs SPECT MPI; Image Quality Excellent or Good [60 days]: Overall summary of sensitivity of flurpiridaz F18 PET MPI (qualitative image quality of excellent or good) vs. SPECT MPI by majority rule vs. truth standard(angio >/=50% stenosis and confirmed MI). Value reported is the number of true positives, i.e. True Positive: Patients with abnormal MPI and disease positive by the truth standard
• Overall Summary of Specificity of PET MPI vs SPECT MPI; Image Quality of Excellent or Good [60 days]: Overall summary of specificity of flurpiridaz F18 PET MPI (qualitative, image quality excellent or good) vs. SPECT MPI by majority rule vs truth standard (angio >/=50% stenosis and confirmed MI). Value represents the number of true negative, i.e. True Negative: Patients with normal MPI and disease negative by the truth standard
• Image Quality of Rest and Stress (PET vs SPECT). [60 days]: Overall summary of rest and stress image quality for flurpiridaz F18 PET MPI and SPECT MPI by majority rule. Value represents the number of subject images evaluated as excellent/good and fair/poor
• Diagnostic Certainty in PET MPI and SPECT MPI [60 days]: Overall summary of diagnostic certainty in flurpiridaz F18 PET MPI and SPECT MPI by majority rule

Sex: All, ages: 18 Years to any

Inclusion Criteria:

Invasive Coronary Angiography. Men or Women age 18 or older - see protocol for additional details.

Exclusion Criteria:

Women who are pregnant, lactating, or of child bearing potential who are not practicing birth control.

Unstable cardiac status. History of coronary artery bypass graft. History of percutaneous coronary intervention within the past six months. See protocol for additional details.

Participant flow

Outcome results

• Diagnostic Efficacy of Flurpiridaz F 18 PET Myocardial Perfusion Imaging (MPI) Sensitivity Versus SPECT Myocardial Perfusion Imaging Sensitivity (Primary), Number, Proportion of true positive cases: Flurpiridaz F18 PET MPI .719 (.670 to .763) (p <0.001)
• Diagnostic Efficacy of Flurpiridaz F18 PET MPI Sensitivity Versus SPECT MPI Sensitivity in Subgroups: Pharmacologic Stress, Females and BMI>/=30. (Secondary), Number, proportion of true postives: Flurpiridaz F18 PET MPI 0.736 (.679 to .785) (p <0.001)
• Diagnostic Efficacy of Flurpiridaz F18 PET MPI Specificity Versus SPECT Specificity in Subgroups: Pharmacologic Stress, Females and BMI>/=30. (Secondary), Number, proportion of true negatives: Flurpiridaz F18 PET MPI .773 (.720 to .819) (p 0.891)
• Diagnostic Performance Evaluation of Localization of CAD for Sensitivity (PETVsSPECT). (Secondary), Number, Proportion of true positives: Flurpiridaz F 18 .495 (.430 to .561) (p <0.001)
• Diagnostic Performance Evaluation of Localization of CAD for Specificity (PETVsSPECT). (Secondary), Number, proportion of true negatives: Flurpiridaz F 18 .867 (.835 to .893) (p .379)
• Diagnositic Performance Evaluation of Multivessel Disease (PETvsSPECT). (Secondary), Number, proportion of true positives: Flurpiridaz F18 PET MPI .410 (.340 to .484) (p <0.001)
• Diagnositic Performance Evaluation of Multivessel Disease (PETvsSPECT). (Secondary), Number, proportion of true negatives: Flurpiridaz F18 PET MPI .882 (.853 to .906) (p 0.827)
• Overall Summary of Sensitivity of PET MPI vs SPECT MPI; Image Quality Excellent or Good (Secondary), Number, proportion of true positives: Flurpiridaz F18 PET MPI .711 (.658 to .759) (p <0.001)
• Diagnostic Efficacy of Flurpiridaz PET MPI Specificity Versus SPECT MPI Specificity (Primary), Number, Proportion of true negatives: Flurpiridaz F18 .762 (.718 to .801) (p .945)
• Overall Summary of Specificity of PET MPI vs SPECT MPI; Image Quality of Excellent or Good (Secondary), Number, proportion of true negatives: Flurpiridaz F18 PET MPI .769 (.721 to .811) (p 0.954)
• Image Quality of Rest and Stress (PET vs SPECT). (Secondary), Number, percent of images: Flurpiridaz F18 PET MPI .891 (p <0.001)
• Diagnostic Certainty in PET MPI and SPECT MPI (Secondary), Number, proportion of patients: Flurpiridaz F 18 0.862 (p <0.001)

Adverse events

Time frame: Adverse events occurring from the time of flurpiridaz F 18 rest administration through 14-17 day safety follow up

Serious adverse events by term

Other adverse events by term

• Results publication: Lopez DM, Huck DM, Divakaran S, Brown JM, Weber BN, Lemley M, Builoff V, Shanbhag A, Lan Z, Buckley C, Al-Mallah MH, Dorbala S, Blankstein R, Slomka P, Di Carli MF. Utility of 18F-Flurpiridaz PET Relative Flow Reserve in Differentiating Obstructive From Nonobstructive Coronary Artery Disease. Circ Cardiovasc Imaging. 2025 Nov;18(11):e018323. doi: 10.1161/CIRCIMAGING.125.018323. Epub 2025 Oct 9. PMID 41064867
• Results publication: Poitrasson-Riviere A, Moody JB, Renaud JM, Hagio T, Arida-Moody L, Buckley CJ, Al-Mallah MH, Nallamothu BK, Weinberg RL, Ficaro EP, Murthy VL. Integrated myocardial flow reserve (iMFR) assessment: optimized PET blood flow quantification for diagnosis of coronary artery disease. Eur J Nucl Med Mol Imaging. 2023 Dec;51(1):136-146. doi: 10.1007/s00259-023-06455-2. Epub 2023 Oct 9. PMID 37807004
• Results publication: Hagio T, Moody JB, Poitrasson-Riviere A, Renaud JM, Pierce L, Buckley C, Ficaro EP, Murthy VL. Multi-center, multi-vendor validation of deep learning-based attenuation correction in SPECT MPI: data from the international flurpiridaz-301 trial. Eur J Nucl Med Mol Imaging. 2023 Mar;50(4):1028-1033. doi: 10.1007/s00259-022-06045-8. Epub 2022 Nov 19. PMID 36401636
• Results publication: Maddahi J, Lazewatsky J, Udelson JE, Berman DS, Beanlands RSB, Heller GV, Bateman TM, Knuuti J, Orlandi C. Phase-III Clinical Trial of Fluorine-18 Flurpiridaz Positron Emission Tomography for Evaluation of Coronary Artery Disease. J Am Coll Cardiol. 2020 Jul 28;76(4):391-401. doi: 10.1016/j.jacc.2020.05.063. PMID 32703509

• Cesare Orlandi, MD, Study director, Lantheus Medical Imaging