Coronary Artery DiseaseFLARENCT07761728
The FLARE (Flurpiridaz vs. Rubidium Evaluation) Trial
An observational study of Coronary Artery Disease and Coronary Microvascular Disease, run by University of California, Los Angeles at 1 site in United States.
Trial summary
This study seeks to evaluate if the diagnostic performance of 18F-flurpiridaz positron emission tomography (PET) myocardial perfusion imaging (MPI), given the radiotracer's properties, is non-inferior to the currently most widely utilized PET MPI radiopharmaceutical, 82Rb-chloride. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Coronary Microvascular Disease
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Aug 2025to Jan 2027
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients scheduled for a clinically indicated 82Rb-Chloride PET MPI at the West Los Angeles Veterans Affairs Medical Center / Greater Los Angeles Veterans Affairs Healthcare System.
Who may be able to join
- Patient scheduled for a clinically indicated 82Rb-chloride PET MPI
- Age ≥ 18 years
- Ability to provide consent
Who cannot join
- Previous participation in a 18F-flurpiridaz clinical trial
- Prior myocardial infarction
- Prior coronary revascularization (percutaneous coronary intervention and/or coronary artery bypass grafting)
- History of orthotopic heart transplantation
- Inability to control heart rate < 65 bpm
- Frequent ventricular or atrial ectopy leading to irregular cardiac rhythm
- Creatinine ≥ 1.4 mg/dL
- Pregnant or breast-feeding status
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
West Los Angeles Veterans Affairs Medical Center
Los Angeles, California, 90073
About this study
Official title: Comparative Evaluation of 18F-Flurpiridaz and 82Rb-Chloride PET Myocardial Perfusion Imaging: The FLARE (Flurpiridaz vs. Rubidium Evaluation) Trial
This study seeks to evaluate if the diagnostic performance of 18F-flurpiridaz positron emission tomography (PET) myocardial perfusion imaging (MPI), given the radiotracer's properties, is non-inferior to the currently most widely utilized PET MPI radiopharmaceutical, 82Rb-chloride.
Read the detailed description
- Patients will undergo a clinically indicated rest/stress 82Rb-chloride positron emission tomography (PET) myocardial perfusion imaging (MPI) and will return to the nuclear cardiology laboratory within 1-30 days to undergo a 18F-flurpiridaz PET MPI and coronary CT angiogram. A rest 18F-flurpiridaz PET MPI will be acquired first, followed by a stress 18F-flurpiridaz PET MPI. The waiting period between the rest and stress 18F-flurpiridaz PET acquisitions will be ≥ 30 minutes. The rest dose will be 2.5-3.0 mCi, and the pharmacological stress dose will be 6.0-6.5 mCi. All PET MPI studies will be conducted using regadenoson as the pharmacologic stress agent.
- 18F-flurpiridaz and 82Rb-chloride PET MPI scans will be interpreted by three expert visual readers in a blinded manner. Both Image quality and diagnostic certainty will be classified using a five-point scale. If the study is abnormal, the perfusion defect will further be categorized as reversible or fixed. Relative perfusion and myocardial blood flow quantification will be obtained using validated software methods.
- Coronary CT angiograms will similarly be analyzed in a blinded manner by a core lab. Coronary segments with a diameter ≥1.5 mm will be included in the analysis. Each segment will be evaluated for the presence or absence of coronary atherosclerosis, defined as any tissue structure >1 mm^2 within the coronary artery wall differentiated from the surrounding epicardial tissue, epicardial fat, or the vessel lumen itself. Maximal stenosis ratios as well as atherosclerotic plaque characteristics and CT-derived fractional flow reserve (FFR) will be obtained in each coronary territory.
- The paired difference between 18F-flurpiridaz and 82Rb-chloride PET MPI will be evaluating by calculating the receiver operating characteristic area under the curve (ROC AUC) for the sensitivity and specificity of blinded visual reads, automated relative perfusion quantitation, and myocardial blood flow quantification, as well as for image quality and diagnostic certainty assessment.
- Keywords
- Myocardial Perfusion Imaging, Nuclear Cardiology, Positron Emission Tomography, Cardiac CT
- Medical subject headings
- Coronary Artery Disease, Microvascular Angina
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients Undergoing Myocardial Perfusion Imaging | Patients scheduled for a clinically indicated myocardial perfusion imaging study with 82Rb-chloride who subsequently undergo MPI with 18F-flurpiridaz as well as a CT coronary angiogram. |
What is being measured
The primary outcome is the main question the study is designed to answer.
18F-Flurpiridaz Diagnostic Performance
The diagnostic performance of 18F-flurpiridaz compared to 82Rb-chloride PET myocardial perfusion imaging by expert readers using coronary CT angiography as the reference standard
- Diagnostic performances will be analyzed on a per-vessel and a per-patient basis using coronary artery disease (CAD) ≥50% and ≥70% stenoses as significance cutoffs and CT-based fractional flow-reserve (FFR) ≤0.80 at the lesion level and at the distal vessel level
Measured: From enrollment to completion of CT coronary angiography, an average of 10 days
Secondary outcomes (2)
Relative Perfusion Analysis
Comparison of automated relative perfusion quantitation markers (summed stress score, summed difference score, total perfusion deficit) between 18F-flurpiridaz and 82Rb-chloride PET MPI using validated software methods
Measured: From enrollment to completion of 18F-flurpiridaz PET MPI, an average of 10 days
Myocardial Blood Flow Quantification
Comparison of myocardial blood flow and myocardial flow reserve quantification between 18F-flurpiridaz and 82Rb-chloride PET MPI using validated software methods
Measured: From enrollment to completion of 18F-flurpiridaz PET MPI, an average of 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2026
- Study start13 Aug 2025
- Primary completionDec 2026 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- VA Greater Los Angeles Healthcare System
- Responsible party
- Principal investigator, Rene R. Sevag Packard, MD, PhD, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07761728
- Sponsor's protocol ID
- IRBNet 1848898-1
- Other IDs
- GEHC ISRC_FPZ-23-03
- Acronym
- FLARE
- Status last verified
- Aug 2026
- First submitted
- 26 Jul 2026
- Last updated
- 17 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chen M, Almeida SO, Sayre JW, Karlsberg RP, Packard RRS. Distal-vessel fractional flow reserve by computed tomography to monitor epicardial coronary artery disease. Eur Heart J Cardiovasc Imaging. 2024 Jan 29;25(2):163-172. doi: 10.1093/ehjci/jead229.
PubMed 37708371Sonck J, Nagumo S, Norgaard BL, Otake H, Ko B, Zhang J, Mizukami T, Maeng M, Andreini D, Takahashi Y, Jensen JM, Ihdayhid A, Heggermont W, Barbato E, Mileva N, Munhoz D, Bartunek J, Updegrove A, Collinsworth A, Penicka M, Van Hoe L, Leipsic J, Koo BK, De Bruyne B, Collet C. Clinical Validation of a Virtual Planner for Coronary Interventions Based on Coronary CT Angiography. JACC Cardiovasc Imaging. 2022 Jul;15(7):1242-1255. doi: 10.1016/j.jcmg.2022.02.003. Epub 2022 Apr 13.
PubMed 35798401Griffin WF, Choi AD, Riess JS, Marques H, Chang HJ, Choi JH, Doh JH, Her AY, Koo BK, Nam CW, Park HB, Shin SH, Cole J, Gimelli A, Khan MA, Lu B, Gao Y, Nabi F, Nakazato R, Schoepf UJ, Driessen RS, Bom MJ, Thompson R, Jang JJ, Ridner M, Rowan C, Avelar E, Genereux P, Knaapen P, de Waard GA, Pontone G, Andreini D, Earls JP. AI Evaluation of Stenosis on Coronary CTA, Comparison With Quantitative Coronary Angiography and Fractional Flow Reserve: A CREDENCE Trial Substudy. JACC Cardiovasc Imaging. 2023 Feb;16(2):193-205. doi: 10.1016/j.jcmg.2021.10.020. Epub 2022 Feb 16.
PubMed 35183478Abbara S, Blanke P, Maroules CD, Cheezum M, Choi AD, Han BK, Marwan M, Naoum C, Norgaard BL, Rubinshtein R, Schoenhagen P, Villines T, Leipsic J. SCCT guidelines for the performance and acquisition of coronary computed tomographic angiography: A report of the society of Cardiovascular Computed Tomography Guidelines Committee: Endorsed by the North American Society for Cardiovascular Imaging (NASCI). J Cardiovasc Comput Tomogr. 2016 Nov-Dec;10(6):435-449. doi: 10.1016/j.jcct.2016.10.002. Epub 2016 Oct 12.
PubMed 27780758Bourque JM, Hanson CA, Agostini D, Bateman TM, Bax JJ, Beanlands RSB, Berman DS, Garcia EV, Heller GV, Knuuti J, Tamaki N, Udelson JE, Maddahi J. Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging. J Nucl Cardiol. 2021 Jun;28(3):1105-1116. doi: 10.1007/s12350-021-02527-8. Epub 2021 Jan 31.
PubMed 33521873Packard RRS, Lazewatsky JL, Orlandi C, Maddahi J. Diagnostic Performance of PET Versus SPECT Myocardial Perfusion Imaging in Patients with Smaller Left Ventricles: A Substudy of the 18F-Flurpiridaz Phase III Clinical Trial. J Nucl Med. 2021 Jun 1;62(6):849-854. doi: 10.2967/jnumed.120.252007. Epub 2020 Nov 27.
PubMed 33246979Maddahi J, Bengel F, Czernin J, Crane P, Dahlbom M, Schelbert H, Sparks R, Phelps M, Lazewatsky J. Dosimetry, biodistribution, and safety of flurpiridaz F 18 in healthy subjects undergoing rest and exercise or pharmacological stress PET myocardial perfusion imaging. J Nucl Cardiol. 2019 Dec;26(6):2018-2030. doi: 10.1007/s12350-018-01484-z. Epub 2018 Nov 28.
PubMed 30488323Packard RRS, Cooke CD, Van Train KF, Votaw JR, Sayre JW, Lazewatsky JL, Champagne KM, Orlandi C, Garcia EV, Maddahi J. Development, diagnostic performance, and interobserver agreement of a 18F-flurpiridaz PET automated perfusion quantitation system. J Nucl Cardiol. 2022 Apr;29(2):698-708. doi: 10.1007/s12350-020-02335-6. Epub 2020 Sep 7.
PubMed 32895856Packard RRS, Votaw JR, Cooke CD, Van Train KF, Garcia EV, Maddahi J. 18F-flurpiridaz positron emission tomography segmental and territory myocardial blood flow metrics: incremental value beyond perfusion for coronary artery disease categorization. Eur Heart J Cardiovasc Imaging. 2022 Nov 17;23(12):1636-1644. doi: 10.1093/ehjci/jeab267.
PubMed 34928321Packard RR, Huang SC, Dahlbom M, Czernin J, Maddahi J. Absolute quantitation of myocardial blood flow in human subjects with or without myocardial ischemia using dynamic flurpiridaz F 18 PET. J Nucl Med. 2014 Sep;55(9):1438-44. doi: 10.2967/jnumed.114.141093. Epub 2014 Jul 28.
PubMed 25071096Maddahi J, Czernin J, Lazewatsky J, Huang SC, Dahlbom M, Schelbert H, Sparks R, Ehlgen A, Crane P, Zhu Q, Devine M, Phelps M. Phase I, first-in-human study of BMS747158, a novel 18F-labeled tracer for myocardial perfusion PET: dosimetry, biodistribution, safety, and imaging characteristics after a single injection at rest. J Nucl Med. 2011 Sep;52(9):1490-8. doi: 10.2967/jnumed.111.092528. Epub 2011 Aug 17.
PubMed 21849402Chen J, Ding Y, Chen M, Gau J, Jen N, Nahal C, Tu S, Chen C, Zhou S, Chang CC, Lyu J, Xu X, Hsiai TK, Packard RRS. Displacement analysis of myocardial mechanical deformation (DIAMOND) reveals segmental susceptibility to doxorubicin-induced injury and regeneration. JCI Insight. 2019 Apr 18;4(8):e125362. doi: 10.1172/jci.insight.125362. eCollection 2019 Apr 18.
PubMed 30996130Packard RRS, Luo Y, Abiri P, Jen N, Aksoy O, Suh WM, Tai YC, Hsiai TK. 3-D Electrochemical Impedance Spectroscopy Mapping of Arteries to Detect Metabolically Active but Angiographically Invisible Atherosclerotic Lesions. Theranostics. 2017 Jun 22;7(9):2431-2442. doi: 10.7150/thno.19184. eCollection 2017.
PubMed 28744325Packard RR, Li D, Budoff MJ, Karlsberg RP. Fractional flow reserve by computerized tomography and subsequent coronary revascularization. Eur Heart J Cardiovasc Imaging. 2017 Feb;18(2):145-152. doi: 10.1093/ehjci/jew148. Epub 2016 Jul 28.
PubMed 27469588Maddahi J, Packard RRS. PET should replace SPECT in cardiac imaging for diagnosis and risk assessment of patients with known or suspected CAD: Pro. J Nucl Cardiol. 2017 Dec;24(6):1955-1959. doi: 10.1007/s12350-015-0300-7. Epub 2017 Apr 10. No abstract available.
PubMed 28397181