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

• Sponsor: Lantheus Medical Imaging (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01347710
• Collaborator: (none)
• Enrollment: 795
• Locations: 81
• Arm: 1
• Duration (Months): 27
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary objective of the study is to assess the diagnostic efficacy (specificity and sensitivity) of flurpiridaz F18 injection PET myocardial perfusion imaging (MPI) compared to single photon emission computed tomography (SPECT) MPI in the detection of significant coronary artery disease (CAD) as defined by invasive coronary angiography (ICA) or a documented history of Myocardial Infarction (MI).

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Flurpiridaz F18; Drug: 99mTechnicium (sestamibi or tetrofosmin)	Phase 3

Detailed Description

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 795 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Phase 3, Open Label, Multicenter Study for the Assessment of Myocardial Perfusion Using Positron Emission Tomography (PET) Imaging of Flurpiridaz F18 Injection in Patients With Suspected or Known Coronary Artery Disease (CAD)
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Flurpiridaz F18 Open-label study of a single dose of Flurpiridaz F18 injection for PET MPI compared to a single dose of 99mTc sestamibi or tetrofosmin for SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization	Drug: Flurpiridaz F18; Injection of Flurpiridaz F18 for the purposes of PET myocardial profusion imaging (MPI) analysis; Other Names: flurpiridaz F 18 ; Drug: 99mTechnicium (sestamibi or tetrofosmin); Injection of 99mTc sestamibi or tetrofosmin for the purposes of SPECT MPI analysis; Other Names: 99mTc sestamibi or 99mTc Tetrofosmin

Outcome Measures

Primary Outcome Measures

1. 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,

2. 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 Outcome Measures

1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology Associates of Mobile, Inc.	Mobile	Alabama	United States	36608
2	Scottsdale Medical Imaging, Ltd.	Scottsdale	Arizona	United States	85258
3	West Side Medical Associates of Los Angeles	Beverly Hills	California	United States	90211
4	USC PET Imaging Science Center	Los Angeles	California	United States	90033
5	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
6	VA West Los Angeles Medical Center	Los Angeles	California	United States	90073
7	UCLA	Los Angeles	California	United States	90095
8	Veterans Affairs Palo Alto Health Care System	Palo Alto	California	United States	94304
9	Cardiovascular Consultants Medical Group	Pleasant Hill	California	United States	94523
10	Northern California PET Imaging Center-Palo Alto	Sacramento	California	United States	95816
11	VA San Diego Healthcare System	San Diego	California	United States	92161
12	UCSF Medical Center	San Francisco	California	United States	94107
13	Yale University	New Haven	Connecticut	United States	06519
14	Alfieri Cardiology	Newark	Delaware	United States	19713
15	Christiana Care Health System	Newark	Delaware	United States	19718
16	Elite Research and Clinical Trials	Aventura	Florida	United States	33180
17	Independent Imaging, LLC	Boynton Beach	Florida	United States	33437
18	Coastal Cardiology Consultants dba The Heart & Vascular Institute of Florida	Clearwater	Florida	United States	33756
19	Florida Heart Associates	Fort Myers	Florida	United States	33907
20	St. Luke's Cardiology Associates	Jacksonville	Florida	United States	32216
21	The Cardiovascular Center, PA	Lake Mary	Florida	United States	32746
22	Florida Hospital/Cardiovascular Institute (Florida Heart Group)	Orlando	Florida	United States	32803
23	South Florida Research Solutions	Pembroke Pines	Florida	United States	33028
24	Memorial Hospital of Tampa	Tampa	Florida	United States	33609
25	Georgia Health Sciences Univ/Med College of GA	Augusta	Georgia	United States	30912
26	South Coast Imaging Center	Savannah	Georgia	United States	31406
27	Gateway Cardiology, PC	Jerseyville	Illinois	United States	62052
28	Norton Cardiovascular Associates	Louisville	Kentucky	United States	40205-3372
29	Biomedical Research Foundation of Northwest Louisiana	Shreveport	Louisiana	United States	71133-8050
30	Maine Research Associates	Auburn	Maine	United States	04210
31	Johns Hopkins University	Baltimore	Maryland	United States	21287-0817
32	Mass General Hospital (MGH)	Boston	Massachusetts	United States	02114
33	Boston University Medical Center	Boston	Massachusetts	United States	02118
34	University of Michigan Health System	Ann Arbor	Michigan	United States	48109-5873
35	Wayne State University - Harper University Hospital	Detroit	Michigan	United States	48201
36	Henry Ford Hospital	Detroit	Michigan	United States	48202
37	St. Mary's Healthcare (Trinity Health)	Grand Rapids	Michigan	United States	49503
38	McLaren Macomb	Mount Clemens	Michigan	United States	48043
39	William Beaumont Hospital	Royal Oak	Michigan	United States	48073-6769
40	Hattiesburg Clinic	Hattiesburg	Mississippi	United States	39401
41	Missouri Cardiovascular Specialists, LLP	Columbia	Missouri	United States	65201
42	Cardiovascular Imaging Technologies (CVIT)	Kansas City	Missouri	United States	64111
43	Saint Louis University School of Medicine	Saint Louis	Missouri	United States	63110
44	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
45	Las Vegas Radiology	Las Vegas	Nevada	United States	89128
46	Montefiore Medical Center	Bronx	New York	United States	10467
47	Mount Sinai Medical Center	New York	New York	United States	10029
48	Columbia University Medical Center	New York	New York	United States	10032
49	St. Francis Hospital	Roslyn	New York	United States	11576
50	University of Cincinnati	Cincinnati	Ohio	United States	45267
51	The Ohio State University	Columbus	Ohio	United States	43210
52	OhioHealth Research Institute	Columbus	Ohio	United States	43214
53	Kettering Medical Center	Kettering	Ohio	United States	45429
54	Pinnacle Health Cardiovascular Institute/ Associated Cardiologists	Harrisburg	Pennsylvania	United States	17110
55	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
56	Presbyterian University Hospital	Pittsburgh	Pennsylvania	United States	15213
57	Berks Cardiologists, Ltd.	Wyomissing	Pennsylvania	United States	19610
58	York Hospital /Wellspan Health	York	Pennsylvania	United States	17405
59	Rhode Island Hospital	Providence	Rhode Island	United States	02903
60	Medical University of South Carolina	Charleston	South Carolina	United States	29425
61	Wellmont CVA Heart Institute	Kingsport	Tennessee	United States	37660
62	Center for Biomedical Research	Knoxville	Tennessee	United States	37909
63	Cardiovascular Research of Knoxville - St. Mary's Health Care System, Inc.	Knoxville	Tennessee	United States	37917
64	Vanderbilt Heart and Vascular Institute	Nashville	Tennessee	United States	37232
65	Dallas VA Medical Center	Dallas	Texas	United States	75216
66	University of Texas Medical Branch	Galveston	Texas	United States	77555-0709
67	Excel Diagnostics and Nuclear Oncology Center	Houston	Texas	United States	77042
68	Katy Cardiology	Katy	Texas	United States	77493
69	West Houston Area Clinical Trial Consultants, LLC	Tomball	Texas	United States	77375
70	University of Virginia Health System	Charlottesville	Virginia	United States	22908
71	McGuire Veteran Affairs Medical Center	Richmond	Virginia	United States	23249
72	Carilion Cardiology Clinic	Roanoke	Virginia	United States	24014
73	Roanoke Heart Institute	Roanoke	Virginia	United States	24014
74	University of Western Ontario	London	Ontario	Canada	N6A 5A5
75	KMH Cardiology and Diagnostic and MRI Centres	Mississauga	Ontario	Canada	L5K 2L3
76	University of Ottawa Heart Institute	Ottawa	Ontario	Canada	K1Y 4W7
77	Centre Hospitalier Universitaire de Sherbrooke (CHUS)	Sherbrooke	Quebec	Canada	J1H 5N4
78	Helsinki University Hospital	Helsinki		Finland	00029 HUS
79	Turku PET Centre	Turku		Finland	FI-20520
80	San Patricio MEDFLIX (San Patricio MRI & CT Center)	Guaynabo		Puerto Rico	00968
81	VA Caribbean Healthcare System	San Juan		Puerto Rico	00921

Sponsors and Collaborators

• Lantheus Medical Imaging

Investigators

• Study Director: Cesare Orlandi, MD, Lantheus Medical Imaging

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lantheus Medical Imaging
• ClinicalTrials.gov Identifier: NCT01347710
• Other Study ID Numbers: BMS747158-301
• First Posted: May 4, 2011
• Last Update Posted: Nov 24, 2020
• Last Verified: Aug 1, 2014

• Keywords provided by Lantheus Medical Imaging: Coronary Artery Disease.; Positron Emission Tomography Myocardial Perfusion Imaging.; Single Positron Emission Computed Tomography.; Flurpiridaz F18 Injection.
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Technetium Tc 99m Sestamibi; Technetium tc-99m tetrofosmin

Study Results

Participant Flow

Arm/Group Title	Flurpiridaz F 18
Arm/Group Description	Open-label study of a single dose of Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization
Period Title: Overall Study
STARTED	795
COMPLETED	764
NOT COMPLETED	31

Baseline Characteristics

Arm/Group Title	Flurpiridaz F 18
Arm/Group Description	Open-label study of a single dose of Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization
Overall Participants	795
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	458 57.6%
>=65 years	337 42.4%
Sex: Female, Male (Count of Participants)
Female	249 31.3%
Male	546 68.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	43 5.4%
Not Hispanic or Latino	708 89.1%
Unknown or Not Reported	44 5.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.3%
Asian	8 1%
Native Hawaiian or Other Pacific Islander	4 0.5%
Black or African American	105 13.2%
White	652 82%
More than one race	0 0%
Unknown or Not Reported	24 3%

Outcome Measures

1. Primary Outcome

Title	Diagnostic Efficacy of Flurpiridaz F 18 PET Myocardial Perfusion Imaging (MPI) Sensitivity Versus SPECT Myocardial Perfusion Imaging Sensitivity
Description	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,
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All safety evaluable patients who had rest and stress flurpiridaz F 18 PET MPI and SPECT MPI procedures resulting in evaluable data, and had evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F18 PET MPI
Arm/Group Description	Open-label study of a single dose of Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization Flurpiridaz F18: Injection of Flurpiridaz F18 for the purposes of PET MPI analysis
Measure Participants	755
PET MPI sensitivity	.719
SPECT MPI Sensitivity	.537

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for sensitivity comparison of flurpiridaz F18 PET MPI vs SPECT MPI for majority rule
	Method	McNemar
	Comments	Two-sided McNemar's (chi-squared) test superiority

2. Secondary Outcome

Title	Diagnostic Efficacy of Flurpiridaz F18 PET MPI Sensitivity Versus SPECT MPI Sensitivity in Subgroups: Pharmacologic Stress, Females and BMI>/=30.
Description	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
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

all safety evaluable patients who had a rest and stress flurpiridaz F18 PET MPI and SPECT MPI procedures resulting in evaluable data and evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F18 PET MPI
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization Flurpiridaz F18: Injection of Flurpiridaz F18 for the purposes of PET MPI analysis
Measure Participants	755
PET sensitivity pharmacologic stress	0.736
SPECT sensitivity pharmacologic stress	0.533
PET sensitivity in females	0.644
SPECT sensitivity in females	0.356
PET sensitivity BMI >/=30	0.722
SPECT sensitivity BMI >/=30	0.533

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-Value for sensitivity comparison of flurpiridaz F18 PET MPI vs SPECT MPI for majority rule in patients under going pharmacologic stress
	Method	McNemar
	Comments	Two-sided McNemar's (chi-squared) test superiority

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-Value for sensitivity comparison of flurpiridaz F18 PET MPI vs. SPECT MPI for majority rule in females
	Method	McNemar
	Comments	p-Value based on two-sided McNemar's (Chi-squared) test superiority

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-Value for sensitivity comparison of flurpiridaz F18 PET MPI vs SPECT MPI for majority rule in patients with BMI >/=30
	Method	McNemar
	Comments	p-Value based on two-sided McNemar's (Chi-squared) test superiority

3. Secondary Outcome

Title	Diagnostic Efficacy of Flurpiridaz F18 PET MPI Specificity Versus SPECT Specificity in Subgroups: Pharmacologic Stress, Females and BMI>/=30.
Description	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
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

all safety evaluable patients who had a rest and stress flurpiridaz F18 PET MPI and SPECT MPI procedures resulting in evaluable data and evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F18 PET MPI
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization Flurpiridaz F18: Injection of Flurpiridaz F18 for the purposes of PET MPI analysis
Measure Participants	755
PET MPI specificity pharmacological stress	.773
SPECT MPI specificity pharmacological stress	.875
PET MPI specificity females	.795
SPECT MPI specificity females	.869
PET MPI specificity BMI >/=30	.777
SPECT MPI specificity BMI >/=30	.850

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Systematic review of literature and meta-analysis of diagnostic efficacy of SPECT MPI to evaluate the performance criteria of SPECT MPI in studies with various levels of control. Analysis of study BMS747158-201. Non-inferiority margin (delta) = 7%
Statistical Test of Hypothesis	p-Value	0.891
	Comments	p-Value for specificity comparison of flurpiridaz F18 PET MPI vs. SPECT MPI for majority rule in patients undergoing pharmacologic stress
	Method	Z test
	Comments	z test for non inferiority for specificity

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Systematic review of literature and meta-analysis of diagnostic efficacy of SPECT MPI to evaluate the performance criteria of SPECT MPI in studies with various levels of control. Analysis of study BMS747158-201. Non-inferiority margin (delta) = 7%
Statistical Test of Hypothesis	p-Value	.546
	Comments	p-Value for specificity comparison of flurpiridaz F18 PET MPI vs. SPECT MPI for majority rule in female patients
	Method	z test
	Comments	z test for non-inferiority for specificity

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Systematic review of literature and meta-analysis of diagnostic efficacy of SPECT MPI to evaluate the performance criteria of SPECT MPI in studies with various levels of control. Analysis of study BMS747158-201. Non-inferiority margin (delta) = 7%
Statistical Test of Hypothesis	p-Value	.538
	Comments	p-Value for specificity comparison of flurpiridaz F18 PET MPI vs. SPECT MPI for majority rule BMI >/=30
	Method	z test
	Comments	z test for non-inferiority for specificity

4. Secondary Outcome

Title	Diagnostic Performance Evaluation of Localization of CAD for Sensitivity (PETVsSPECT).
Description	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
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All safety evaluable patients who had rest and stress flurpiridaz F 18 Flurpiridaz F18 PET MPI and SPECT MPI procedures resulting in evaluable data, and had evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F 18
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization
Measure Participants	755
PET sensitivity LAD	.495
SPECT sensitivity LAD	.333
PET sensitivity LCX	.398
SPECT sensitivity LCX	.251
PET sensitivity RCA	.596
SPECT sensitivity RCA	.476
PET sensitivity Non-LAD	.627
SPECT sensitivity Non-LAD	.464

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-Value for sensitivity comparison of flurpiridaz F18 PET MPI and SPECT MPI for majority rule in the localization of coronary artery disease; LAD
	Method	McNemar
	Comments	Two-sided McNemar (chi-squared) test superiority for sensitivity; LAD

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-Value for sensitivity comparison of flurpiridaz F18 PET MPI and SPECT MPI for majority rule in the localization of coronary artery disease; LCX
	Method	McNemar
	Comments	p-Value based on two-sided McNemar's (Chi-squared) test superiority for sensitivity; LCX

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-Value for sensitivity comparison of flurpiridaz F18 PET MPI and SPECT MPI for majority rule in the localization of coronary artery disease; RCA
	Method	McNemar
	Comments	p-Value based on two-sided McNemar's (Chi-squared) test superiority for sensitivity; RCA

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-Value for sensitivity comparison of flurpiridaz F18 PET MPI and SPECT MPI for majority rule in the localization of coronary artery disease; Non-LAD
	Method	McNemar
	Comments	p-Value based on two-sided McNemar's (Chi-squared) test superiority for sensitivity; Non-LAD

5. Secondary Outcome

Title	Diagnostic Performance Evaluation of Localization of CAD for Specificity (PETVsSPECT).
Description	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
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All safety evaluable patients who had rest and stress flurpiridaz F 18 PET MPI and SPECT MPI procedures resulting in evaluable data, and had evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F 18
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization
Measure Participants	755
PET specificity LAD	.867
SPECT specificity LAD	.932
PET specificity LCX	.904
SPECT specificity LCX	.970
PET specificity RCA	.845
SPECT specificity RCA	.912
PET specificity Non-LAD	.814
SPECT specificity Non-LAD	.923

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Systematic review of literature and meta-analysis of diagnostic efficacy of SPECT MPI to evaluate the performance criteria of SPECT MPI in studies with various levels of control. Analysis of study BMS747158-201. Non-inferiority margin (delta) = 7%
Statistical Test of Hypothesis	p-Value	.379
	Comments	p-Value for specificity comparison of flurpiridaz F18 PET MPI and SPECT MPI for majority rule in the localization of coronary artery disease; LAD
	Method	z Test
	Comments	z test for non-inferiority for specificity; LAD

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Systematic review of literature and meta-analysis of diagnostic efficacy of SPECT MPI to evaluate the performance criteria of SPECT MPI in studies with various levels of control. Analysis of study BMS747158-201. Non-inferiority margin (delta) = 7%
Statistical Test of Hypothesis	p-Value	.358
	Comments	p-Value for specificity comparison of flurpiridaz F18 PET MPI and SPECT MPI for majority rule in the localization of coronary artery disease; LCX
	Method	Z Test
	Comments	z test for non-inferiority for specificity; LCX

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Systematic review of literature and meta-analysis of diagnostic efficacy of SPECT MPI to evaluate the performance criteria of SPECT MPI in studies with various levels of control. Analysis of study BMS747158-201. Non-inferiority margin (delta) = 7%
Statistical Test of Hypothesis	p-Value	.442
	Comments	p-Value for specificity comparison of flurpiridaz F18 PET MPI and SPECT MPI for majority rule in the localization of coronary artery disease; RCA
	Method	z Test
	Comments	z test for non-inferiority for specificity; RCA

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Systematic review of literature and meta-analysis of diagnostic efficacy of SPECT MPI to evaluate the performance criteria of SPECT MPI in studies with various levels of control. Analysis of study BMS747158-201. Non-inferiority margin (delta) = 7%
Statistical Test of Hypothesis	p-Value	.984
	Comments	p-Value for specificity comparison of flurpiridaz F18 PET MPI and SPECT MPI for majority rule in the localization of coronary artery disease; Non-LAD
	Method	z Test
	Comments	z test for non-inferiority for specificity; non-LAD

6. Secondary Outcome

Title	Diagnositic Performance Evaluation of Multivessel Disease (PETvsSPECT).
Description	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
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All safety evaluable patients who had rest and stress flurpiridaz F 18 PET MPI and SPECT MPI procedures resulting in evaluable data, and had evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F18 PET MPI
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization Flurpiridaz F18: Injection of Flurpiridaz F18 for the purposes of PET MPI analysis
Measure Participants	755
PET MPI sensitivity; multivessel disease	.410
SPECT MPI sensitivity; multivessel disease	.275

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-Value of sensitivity for flurpiridaz F18 PET MPI vs. SPECT MPI for majority rule; multivessel disease
	Method	McNemar
	Comments	p-Value based on two-sided McNemar's (Chi squared) test superiority

7. Secondary Outcome

Title	Diagnositic Performance Evaluation of Multivessel Disease (PETvsSPECT).
Description	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
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All safety evaluable patients who had rest and stress flurpiridaz F 18 PET MPI and SPECT MPI procedures resulting in evaluable data, and had evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F18 PET MPI
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization Flurpiridaz F18: Injection of Flurpiridaz F18 for the purposes of PET MPI analysis
Measure Participants	755
PET MPI specificity; multivessel disease	.882
SPECT MPI specificity; multivessel disease	.964

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Systematic review of literature and meta-analysis of diagnostic efficacy of SPECT MPI to evaluate the performance criteria of SPECT MPI in studies with various levels of control. Analysis of study BMS747158-201. Non-inferiority margin (delta) = 7%
Statistical Test of Hypothesis	p-Value	0.827
	Comments	p-Value of specificity for comparison of flurpiridaz F18 PET MPI vs. SPECT MPI in detecting multivessel disease
	Method	z test
	Comments	p-Value based on one-sided z test for non-inferiority

8. Secondary Outcome

Title	Overall Summary of Sensitivity of PET MPI vs SPECT MPI; Image Quality Excellent or Good
Description	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
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All safety evaluable patients who had rest and stress flurpiridaz F 18 PET MPI and SPECT MPI procedures resulting in evaluable data, and had evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F18 PET MPI
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization Flurpiridaz F18: Injection of Flurpiridaz F18 for the purposes of PET MPI analysis
Measure Participants	755
PET MPI sensitivity; image quality excellent/good	.711
SPECT MPI sensitivity image quality excellent/good	.539

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-Value for sensitivity comparison of flurpiridaz F18 PET MPI vs SPECT MPI for majority rule; image quality of excellent or good
	Method	McNemar
	Comments	p-Value based on two-sided McNemar's (Chi-squared) test superiority for sensitivity

9. Primary Outcome

Title	Diagnostic Efficacy of Flurpiridaz PET MPI Specificity Versus SPECT MPI Specificity
Description	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
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

all safety evaluable patients who had rest and stress flurpiridaz F 18 PET MPI and SPECT MPI procedures resulting in evaluable data and had evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F18
Arm/Group Description	Open-label study of a single dose of Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization Flurpiridaz F18: Injection of Flurpiridaz F18 for the purposes of PET MPI analysis
Measure Participants	755
PET MPI Specificity	.762
SPECT MPI Specificity	.868

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Systematic review of literature and meta-analysis of diagnostic efficacy of SPECT MPI to evaluate the performance criteria of SPECT MPI in studies with various levels of control. Analysis of study protocol number BMS747158-201. Non-inferiority margin (delta) = 7%
Statistical Test of Hypothesis	p-Value	.945
	Comments	p-Value for specificity comparison of flurpiridaz F18 PET MPI vs. SPECT MPI
	Method	Z Test
	Comments	one-sided z test for non-inferiority for specificity

10. Secondary Outcome

Title	Overall Summary of Specificity of PET MPI vs SPECT MPI; Image Quality of Excellent or Good
Description	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
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All safety evaluable patients who had rest and stress flurpiridaz F 18 PET MPI and SPECT MPI procedures resulting in evaluable data, and had evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F18 PET MPI
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization Flurpiridaz F18: Injection of Flurpiridaz F18 for the purposes of PET MPI analysis
Measure Participants	755
PET MPI specificity; image quality excellent/good	.769
SPECT MPI specificity image quality excellent/good	.880

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Systematic review of literature and meta-analysis of diagnostic efficacy of SPECT MPI to evaluate the performance criteria of SPECT MPI in studies with various levels of control. Analysis of study BMS747158-201. Non-inferiority margin (delta) = 7%
Statistical Test of Hypothesis	p-Value	0.954
	Comments	p-Value for specificity comparison of flurpiridaz F18 PET MPI vs SPECT MPI for majority rule; image quality excellent/good
	Method	z Test
	Comments	p-Value based on on-sided z test for non-inferiority for specificity

11. Secondary Outcome

Title	Image Quality of Rest and Stress (PET vs SPECT).
Description	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
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All safety evaluable patients who had rest and stress flurpiridaz F 18 PET MPI and SPECT MPI procedures resulting in evaluable data, and had evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F18 PET MPI
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization Flurpiridaz F18: Injection of Flurpiridaz F18 for the purposes of PET MPI analysis
Measure Participants	755
Rest imaging quality PET MPI; excellent/good	.891
Rest image quality SPECT MPI; excellent/good	.739
Stress image quality PET MPI; excellent/good	.976
Stress image quality SPECT MPI; excellent/good	.869
Rest image quality PET MPI; fair/poor	.109
Rest image quality SPECT MPI; fair/poor	.261
stress image quality PET MPI; fair/poor	.024
Stress image quality SPECT MPI; fair/poor	.131

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments

12. Secondary Outcome

Title	Diagnostic Certainty in PET MPI and SPECT MPI
Description	Overall summary of diagnostic certainty in flurpiridaz F18 PET MPI and SPECT MPI by majority rule
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All safety evaluable patients who had rest and stress flurpiridaz F 18 PET MPI and SPECT MPI procedures resulting in evaluable data, and had evaluable invasive coronary angiography

Arm/Group Title	Flurpiridaz F 18
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization
Measure Participants	755
PET definitely normal/abnormal	0.862
PET probably/equivocal	0.138
SPECT definitely normal/abnormal	0.799
SPECT probably/equivocal	0.201

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flurpiridaz F18 PET MPI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	McNemar
	Comments	p-Values are from 2-sided McNemar's test of comparison in proportion of patients with definitely diagnositic certainty between PET and SPECT

Adverse Events

Time Frame	Adverse events occurring from the time of flurpiridaz F 18 rest administration through 14-17 day safety follow up
Adverse Event Reporting Description	Affected represents patients with at least one serious adverse event and/or adverse event
Arm/Group Title	Flurpiridaz F 18
Arm/Group Description	Open-label study of a single dose Flurpiridaz F18 injection for PET MPI compared to SPECT MPI in patients with suspected or known coronary artery disease referred for coronary catheterization
All Cause Mortality
	Flurpiridaz F 18
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Flurpiridaz F 18
	Affected / at Risk (%)	# Events
Total	20/795 (2.5%)
Cardiac disorders
Angina Pectoris	6/795 (0.8%)	6
Atrial Flutter	1/795 (0.1%)	1
Cardiac Failure Congestive	1/795 (0.1%)	1
Cardiogenic Shock	1/795 (0.1%)	1
Ventricular Tachycardia	2/795 (0.3%)	2
Gastrointestinal disorders
Inguinal Hernia	1/795 (0.1%)	1
General disorders
Catheter Site Haemorrhage	1/795 (0.1%)	1
Non-Cardiac Chest Pain	1/795 (0.1%)	1
Infections and infestations
Pneumonia	1/795 (0.1%)	1
Metabolism and nutrition disorders
Hypoglycaemia	1/795 (0.1%)	1
Nervous system disorders
Dizziness	1/795 (0.1%)	1
Headache	1/795 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	1/795 (0.1%)	1
Dyspnoea	1/795 (0.1%)	1
Pulmonary Embolism	1/795 (0.1%)	1
Vascular disorders
Hypotension	1/795 (0.1%)	1
Peripheral Arterial Occlusive Disease	1/795 (0.1%)	1
Other (Not Including Serious) Adverse Events
	Flurpiridaz F 18
	Affected / at Risk (%)	# Events
Total	555/795 (69.8%)
Cardiac disorders
Angina Pectoris	119/795 (15%)	119
Gastrointestinal disorders
Nausea	44/795 (5.5%)	44
General disorders
Fatigue	70/795 (8.8%)	70
Non-Cardiac Chest Pain	58/795 (7.3%)	58
Investigations
Electrocardiogram ST Segment Depressions	75/795 (9.4%)	75
Nervous system disorders
Dizziness	43/795 (5.4%)	43
Headache	129/795 (16.2%)	129
Respiratory, thoracic and mediastinal disorders
Dyspnoea	200/795 (25.2%)	200
Surgical and medical procedures
Percutaneous coronary intervention	72/795 (9.1%)	72
Vascular disorders
Flushing	60/795 (7.5%)	60

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.