2. Academic Validation
  3. Phase-III Clinical Trial of Fluorine-18 Flurpiridaz Positron Emission Tomography for Evaluation of Coronary Artery Disease

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.
Jamshid Maddahi 1,  Joel Lazewatsky 2,  James E Udelson 3,  Daniel S Berman 4,  Rob S B Beanlands 5,  Gary V Heller 6,  Timothy M Bateman 7,  Juhani Knuuti 8,  Cesare Orlandi 2
Affiliations

Affiliations

  • 1 Division of Nuclear Medicine, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California; Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California. Electronic address: [email protected].
  • 2 Lantheus Medical Imaging, North Billerica, Massachusetts.
  • 3 Tufts Medical Center, Boston, Massachusetts.
  • 4 Cedars-Sinai Medical Center, Los Angeles, California.
  • 5 University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
  • 6 Morristown Medical Center, Morristown, New Jersey.
  • 7 Mid America Heart Institute, Saint Luke's Hospital, Kansas City, Missouri.
  • 8 Turku University, Turku, Finland.
PMID: 32703509 DOI: 10.1016/j.jacc.2020.05.063
Abstract

Background: Fluorine-18 flurpiridaz is a novel positron emission tomography (PET) myocardial perfusion imaging tracer.

Objectives: This study sought to assess the diagnostic efficacy of flurpiridaz PET versus technetium-99m-labeled single photon emission computed tomography SPECT for the detection and evaluation of coronary artery disease (CAD), defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). Flurpiridaz safety was also evaluated.

Methods: In this phase III prospective multicenter clinical study, 795 patients with known or suspected CAD from 72 clinical sites in the United States, Canada, and Finland were enrolled. A total of 755 patients were evaluable, and the mean age was 62.3 ± 9.5 years, 31% were women, 55% had body mass index ≥30 kg/m2, and 71% had pharmacological stress. Patients underwent 1-day rest-stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m-labeled SPECT and ICA. Images were read by 3 experts blinded to clinical and ICA data.

Results: Sensitivity of flurpiridaz PET (for detection of ≥50% stenosis by ICA) was 71.9% (95% confidence interval [CI]: 67.0% to 76.3%), significantly (p < 0.001) higher than SPECT (53.7% [95% CI: 48.5% to 58.8%]), while specificity did not meet the prespecified noninferiority criterion (76.2% [95% CI: 71.8% to 80.1%] vs. 86.6% [95% CI: 83.2% to 89.8%]; p = NS). Receiver-operating characteristic curve analysis demonstrated superior discrimination of CAD by flurpiridaz PET versus SPECT in the overall population, in women, obese patients, and patients undergoing pharmacological stress testing (p < 0.001 for all). Flurpiridaz PET was superior to SPECT for defect size (p < 0.001), image quality (p < 0.001), diagnostic certainty (p < 0.001), and radiation exposure (6.1 ± 0.4 mSv vs. 13.4 ± 3.2 mSv; p < 0.001). Flurpiridaz PET was safe and well tolerated.

Conclusions: Flurpiridaz PET myocardial perfusion imaging shows promise as a new tracer for CAD detection and assessment of women, obese patients, and patients undergoing pharmacological stress testing. A second phase III Food and Drug Administration trial is ongoing. (A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients with CAD; NCT01347710).

Keywords

SPECT; coronary artery disease; flurpiridaz; myocardial perfusion imaging; positron emission tomography.

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