The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03354273
Recruitment Status : Completed
First Posted : November 27, 2017
Results First Posted : July 12, 2023
Last Update Posted : July 12, 2023
Sponsor:
Collaborator:
Pharmaceutical Product Development, LLC
Information provided by (Responsible Party):
GE Healthcare

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Diagnostic
Condition Coronary Artery Disease (CAD)
Interventions Drug: PET MPI
Drug: SPECT MPI
Drug: Pharmacological stress agents
Enrollment 730
Recruitment Details This study was conducted at 48 centers in Finland, France, Germany, Netherlands, United States and Canada from 05 June 2018 to 05 May 2022.
Pre-assignment Details A total 730 participants signed informed consent and were enrolled, of these, 604 participants received greater than or equal to (>=) 1 dose of Flurpiridaz (18F) Injection in this study.
Arm/Group Title Flurpiridaz (18F): All Participants
Hide Arm/Group Description

Participants received 2 intravenous (IV) boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the invasive coronary angiography (ICA). Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 millicurie (mCi) (520 megabecquerel [MBq]) for an individual participant. Flurpiridaz was administered on Study Day 1.

Single photon emission computed tomography (SPECT) agents 99mTc-based myocardial tracers, example [99mTc]tetrofosmin or [99mTc]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection positron emission tomography (PET) myocardial perfusion imaging (MPI). Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Period Title: Overall Study
Started 730 [1]
Safety Population (Treated) 604
Modified Intent-to-Treat (MITT) Population 578
Secondary Modified Intent-to-Treat (SMITT) Population 578
Completed 578
Not Completed 152
Reason Not Completed
Adverse Event             5
Screen Failure             21
Withdrawal by Subject             34
Technical Problems             30
Lost to Follow-up             4
Investigator Decision             3
Investigational Medicinal Product (IMP) Supply Issues             21
Issues With Performing Invasive Coronary Angiography (ICA)             20
COVID-19 Restrictions             9
Other             5
[1]
Participants who signed informed consent form and were enrolled in the study.
Arm/Group Title Flurpiridaz (18F): All Participants
Hide Arm/Group Description

Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1.

SPECT agents 99mTc-based myocardial tracers, example [99mTc]tetrofosmin or [99mTc]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Overall Number of Baseline Participants 730
Hide Baseline Analysis Population Description
The enrolled population consisted of all participants who signed informed consent.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 730 participants
63.9  (9.26)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 730 participants
Female
235
  32.2%
Male
495
  67.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 730 participants
Hispanic or Latino
98
  13.4%
Not Hispanic or Latino
512
  70.1%
Unknown or Not Reported
120
  16.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 730 participants
American Indian or Alaska Native
1
   0.1%
Asian
10
   1.4%
Native Hawaiian or Other Pacific Islander
3
   0.4%
Black or African American
55
   7.5%
White
579
  79.3%
More than one race
0
   0.0%
Unknown or Not Reported
82
  11.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 730 participants
Canada
129
  17.7%
United States
412
  56.4%
Finland
36
   4.9%
France
71
   9.7%
Germany
3
   0.4%
Netherlands
79
  10.8%
1.Primary Outcome
Title 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
Hide Description 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.
Time Frame Up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
The MITT population included all participants who completed the rest and stress Flurpiridaz (18F) Injection PET MPI procedures and who had evaluable truth standard data. Here, "overall number of participants analyzed" signifies participants who were analyzed for a specific reader (combined sensitivity or specificity) and "number analyzed" signifies participants who were evaluable for specified categories.
Arm/Group Title Flurpiridaz (18F)
Hide Arm/Group Description:

Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1.

SPECT agents 99mTc-based myocardial tracers, example [99mTc]tetrofosmin or [99mTc]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Overall Number of Participants Analyzed 578
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent
Reader 1: Sensitivity Number Analyzed 249 participants
77.1
(71.9 to 82.3)
Reader 1: Specificity Number Analyzed 329 participants
65.7
(60.5 to 70.8)
Reader 2: Sensitivity Number Analyzed 249 participants
73.5
(68.0 to 79.0)
Reader 2: Specificity Number Analyzed 329 participants
69.6
(64.6 to 74.6)
Reader 3: Sensitivity Number Analyzed 249 participants
88.8
(84.8 to 92.7)
Reader 3: Specificity Number Analyzed 329 participants
52.6
(47.2 to 58.0)
Majority Rule: Sensitivity Number Analyzed 249 participants
80.3
(75.4 to 85.3)
Majority Rule: Specificity Number Analyzed 329 participants
63.8
(58.6 to 69.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F)
Comments Reader 1: Sensitivity
Type of Statistical Test Other
Comments Sensitivity was compared to a pre-specified threshold of 60%.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method One-sided z-tests
Comments The hypothesis tests were one-sided z-tests with a significance level of 0.025.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F)
Comments Reader 1: Specificity
Type of Statistical Test Other
Comments Specificity was compared to a pre-specified threshold of 60%.
Statistical Test of Hypothesis P-Value 0.0182
Comments [Not Specified]
Method One-sided z-tests
Comments The hypothesis tests were one-sided z-tests with a significance level of 0.025.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F)
Comments Reader 2: Sensitivity
Type of Statistical Test Other
Comments Sensitivity was compared to a pre-specified threshold of 60%.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method One-sided z-tests
Comments The hypothesis tests were one-sided z-tests with a significance level of 0.025.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F)
Comments Reader 2: Specificity
Type of Statistical Test Other
Comments Specificity was compared to a pre-specified threshold of 60%.
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method One-sided z-tests
Comments The hypothesis tests were one-sided z-tests with a significance level of 0.025.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F)
Comments Reader 3: Sensitivity
Type of Statistical Test Other
Comments Sensitivity was compared to a pre-specified threshold of 60%.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method One-sided z-tests
Comments The hypothesis tests were one-sided z-tests with a significance level of 0.025.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F)
Comments Reader 3: Specificity
Type of Statistical Test Other
Comments Specificity was compared to a pre-specified threshold of 60%.
Statistical Test of Hypothesis P-Value 0.9970
Comments [Not Specified]
Method One-sided z-tests
Comments The hypothesis tests were one-sided z-tests with a significance level of 0.025.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F)
Comments Majority Rule: Sensitivity
Type of Statistical Test Other
Comments Sensitivity was compared to a pre-specified threshold of 60%.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method One-sided z-tests
Comments The hypothesis tests were one-sided z-tests with a significance level of 0.025.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F)
Comments Majority Rule: Specificity
Type of Statistical Test Other
Comments Specificity was compared to a pre-specified threshold of 60%.
Statistical Test of Hypothesis P-Value 0.0781
Comments [Not Specified]
Method One-sided z-tests
Comments The hypothesis tests were one-sided z-tests with a significance level of 0.025.
2.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
The SMITT population included the participants who completed the rest and stress SPECT MPI (if the participant's SPECT MPI was "off-study," that SPECT MPI had to meet minimal quality standards, as specified by the imaging core lab). Here, "overall number of participants analyzed" signifies participants who were analyzed for a specific reader (combined sensitivity or specificity) and "number analyzed" signifies participants who were evaluable for specified categories.
Arm/Group Title Flurpiridaz (18F) PET MPI SPECT MPI
Hide Arm/Group Description:

Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.

SPECT agents 99mTc-based myocardial tracers, example [99mTc]tetrofosmin or [99mTc]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Overall Number of Participants Analyzed 578 578
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent
Reader 1: Sensitivity Number Analyzed 249 participants 249 participants
77.1
(71.9 to 82.3)
62.7
(56.6 to 68.7)
Reader 1: Specificity Number Analyzed 329 participants 329 participants
65.7
(60.5 to 70.8)
63.2
(58.0 to 68.4)
Reader 2: Sensitivity Number Analyzed 249 participants 249 participants
73.5
(68.0 to 79.0)
60.6
(54.6 to 66.7)
Reader 2: Specificity Number Analyzed 329 participants 329 participants
69.6
(64.6 to 74.6)
64.7
(59.6 to 69.9)
Reader 3: Sensitivity Number Analyzed 249 participants 249 participants
88.8
(84.8 to 92.7)
75.5
(70.2 to 80.8)
Reader 3: Specificity Number Analyzed 329 participants 329 participants
52.6
(47.2 to 58.0)
51.4
(46.0 to 56.8)
Majority Rule: Sensitivity Number Analyzed 249 participants 249 participants
80.3
(75.4 to 85.3)
68.7
(62.9 to 74.4)
Majority Rule: Specificity Number Analyzed 329 participants 329 participants
63.8
(58.6 to 69.0)
61.7
(56.4 to 67.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 1: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method McNemar
Comments The hypothesis tests were 1-sided McNemar's tests with a significance level of 0.025 for sensitivity.
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 14.5
Confidence Interval (2-Sided) 95%
6.5 to 22.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 1: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 2.4
Confidence Interval (2-Sided) 95%
-4.9 to 9.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 2: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 12.9
Confidence Interval (2-Sided) 95%
4.7 to 21.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 2: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 4.9
Confidence Interval (2-Sided) 95%
-2.1 to 11.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 3: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 13.3
Confidence Interval (2-Sided) 95%
6.6 to 19.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 3: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-6.0 to 8.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Majority Rule: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 11.6
Confidence Interval (2-Sided) 95%
4.1 to 19.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Majority Rule: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
-5.0 to 9.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
The SMITT population included the participants who completed the rest and stress SPECT MPI (if the participant's SPECT MPI was "off-study," that SPECT MPI had to meet minimal quality standards, as specified by the imaging core lab). Here, "overall number of participants analyzed" signifies participants who were analyzed for a specific reader (combined sensitivity or specificity) and "number analyzed" signifies participants who were evaluable for specified categories.
Arm/Group Title Flurpiridaz (18F) PET MPI SPECT MPI
Hide Arm/Group Description:

Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.

SPECT agents 99mTc-based myocardial tracers, example [99mTc]tetrofosmin or [99mTc]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Overall Number of Participants Analyzed 188 188
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent
Reader 1: Sensitivity Number Analyzed 41 participants 41 participants
82.9
(71.4 to 94.4)
58.5
(43.5 to 73.6)
Reader 1: Specificity Number Analyzed 147 participants 147 participants
72.8
(65.6 to 80.0)
63.3
(55.5 to 71.1)
Reader 2: Sensitivity Number Analyzed 41 participants 41 participants
78.0
(65.4 to 90.7)
56.1
(40.9 to 71.3)
Reader 2: Specificity Number Analyzed 147 participants 147 participants
75.5
(68.6 to 82.5)
68.7
(61.2 to 76.2)
Reader 3: Sensitivity Number Analyzed 41 participants 41 participants
92.7
(84.7 to 100.0)
75.6
(62.5 to 88.8)
Reader 3: Specificity Number Analyzed 147 participants 147 participants
59.2
(51.2 to 67.1)
58.5
(50.5 to 66.5)
Majority Rule: Sensitivity Number Analyzed 41 participants 41 participants
82.9
(71.4 to 94.4)
65.9
(51.3 to 80.4)
Majority Rule: Specificity Number Analyzed 147 participants 147 participants
72.8
(65.6 to 80.0)
66.0
(58.3 to 73.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 1: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.0127
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 24.4
Confidence Interval (2-Sided) 95%
5.4 to 43.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 1: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 9.5
Confidence Interval (2-Sided) 95%
-1.2 to 20.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 2: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.0195
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 22.0
Confidence Interval (2-Sided) 95%
2.2 to 41.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 2: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
-3.2 to 16.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 3: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.0174
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 17.1
Confidence Interval (2-Sided) 95%
1.7 to 32.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0240
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-9.9 to 11.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Majority Rule: Sensitivity
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0448
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 17.1
Confidence Interval (2-Sided) 95%
-1.5 to 35.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Majority Rule: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
-3.4 to 17.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
The SMITT population included the participants who completed the rest and stress SPECT MPI (if the participant's SPECT MPI was "off-study," that SPECT MPI had to meet minimal quality standards, as specified by the imaging core lab). Here, "overall number of participants analyzed" signifies participants who were analyzed for a specific reader (combined sensitivity or specificity) and "number analyzed" signifies participants who were evaluable for specified categories.
Arm/Group Title Flurpiridaz (18F) PET MPI SPECT MPI
Hide Arm/Group Description:

Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.

SPECT agents 99mTc-based myocardial tracers, example [99mTc]tetrofosmin or [99mTc]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Overall Number of Participants Analyzed 298 298
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent
Reader 1: Sensitivity Number Analyzed 117 participants 117 participants
72.6
(64.6 to 80.7)
60.7
(51.8 to 69.5)
Reader 1: Specificity Number Analyzed 181 participants 181 participants
68.0
(61.2 to 74.8)
61.3
(54.2 to 68.4)
Reader 2: Sensitivity Number Analyzed 117 participants 117 participants
70.1
(61.8 to 78.4)
63.2
(54.5 to 72.0)
Reader 2: Specificity Number Analyzed 181 participants 181 participants
74.0
(67.6 to 80.4)
62.4
(55.4 to 69.5)
Reader 3: Sensitivity Number Analyzed 117 participants 117 participants
88.0
(82.2 to 93.9)
74.4
(66.4 to 82.3)
Reader 3: Specificity Number Analyzed 181 participants 181 participants
53.6
(46.3 to 60.9)
50.8
(43.5 to 58.1)
Majority Rule: Sensitivity Number Analyzed 117 participants 117 participants
76.9
(69.3 to 84.6)
69.2
(60.9 to 77.6)
Majority Rule: Specificity Number Analyzed 181 participants 181 participants
66.9
(60.0 to 73.7)
61.9
(54.8 to 69.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 1: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.0116
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 12.0
Confidence Interval (2-Sided) 95%
0.0 to 23.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 1: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 6.6
Confidence Interval (2-Sided) 95%
-2.9 to 16.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 2: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.1085
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
-5.2 to 18.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 2: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 11.6
Confidence Interval (2-Sided) 95%
2.1 to 21.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 3: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 13.7
Confidence Interval (2-Sided) 95%
3.8 to 23.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 3: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-6.6 to 12.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Majority Rule: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.0641
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 7.7
Confidence Interval (2-Sided) 95%
-3.6 to 19.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Majority Rule: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 5.0
Confidence Interval (2-Sided) 95%
-4.6 to 14.6
Estimation Comments [Not Specified]
5.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
The SMITT population included the participants who completed the rest and stress SPECT MPI (if the participant's SPECT MPI was "off-study," that SPECT MPI had to meet minimal quality standards, as specified by the imaging core lab). Here, "overall number of participants analyzed" signifies participants who were analyzed for a specific reader (combined sensitivity or specificity) and "number analyzed" signifies participants who were evaluable for specified categories.
Arm/Group Title Flurpiridaz (18F) PET MPI SPECT MPI
Hide Arm/Group Description:

Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.

SPECT agents 99mTc-based myocardial tracers, example [99mTc]tetrofosmin or [99mTc]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
Overall Number of Participants Analyzed 194 194
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent
Reader 1: Sensitivity Number Analyzed 91 participants 91 participants
72.5
(63.4 to 81.7)
61.5
(51.5 to 71.5)
Reader 1: Specificity Number Analyzed 103 participants 103 participants
60.2
(50.7 to 69.6)
56.3
(46.7 to 65.9)
Reader 2: Sensitivity Number Analyzed 91 participants 91 participants
69.2
(59.7 to 78.7)
62.6
(52.7 to 72.6)
Reader 2: Specificity Number Analyzed 103 participants 103 participants
69.9
(61.0 to 78.8)
58.3
(48.7 to 67.8)
Reader 3: Sensitivity Number Analyzed 91 participants 91 participants
90.1
(84.0 to 96.2)
81.3
(73.3 to 89.3)
Reader 3: Specificity Number Analyzed 103 participants 103 participants
47.6
(37.9 to 57.2)
39.8
(30.4 to 49.3)
Majority Rule: Sensitivity Number Analyzed 91 participants 91 participants
75.8
(67.0 to 84.6)
71.4
(62.1 to 80.7)
Majority Rule: Specificity Number Analyzed 103 participants 103 participants
61.2
(51.8 to 70.6)
51.5
(41.8 to 61.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 1: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.0294
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 11.0
Confidence Interval (2-Sided) 95%
-2.6 to 24.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 1: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0117
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 3.9
Confidence Interval (2-Sided) 95%
-8.3 to 16.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 2: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.1444
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 6.6
Confidence Interval (2-Sided) 95%
-7.1 to 20.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 2: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 11.7
Confidence Interval (2-Sided) 95%
-0.4 to 23.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 3: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.0440
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 8.8
Confidence Interval (2-Sided) 95%
-1.3 to 18.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Reader 3: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0022
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 7.8
Confidence Interval (2-Sided) 95%
-4.8 to 20.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Majority Rule: Sensitivity
Type of Statistical Test Superiority
Comments The test of sensitivity comparison between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a 1-sided McNemar's test at a significance level of 0.025 using 1-sided McNemar's tests.
Statistical Test of Hypothesis P-Value 0.2164
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 4.4
Confidence Interval (2-Sided) 95%
-8.4 to 17.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Flurpiridaz (18F) PET MPI, SPECT MPI
Comments Majority Rule: Specificity
Type of Statistical Test Non-Inferiority
Comments The test of specificity noninferiority between Flurpiridaz (18F) Injection PET MPI and SPECT MPI was performed with a paired test for noninferiority at a 1-sided significance level of 0.025 using Nam's RMLE method (margin=0.1).
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Nam's RMLE
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between PET MPI and SPECT MPI
Estimated Value 9.7
Confidence Interval (2-Sided) 95%
-2.6 to 22.0
Estimation Comments [Not Specified]
Time Frame From the time of informed consent to end of follow up (up to 77 days)
Adverse Event Reporting Description The Safety population consisted of all enrolled participants who received >=1 dose of Flurpiridaz (18F) Injection in the study.
 
Arm/Group Title Flurpiridaz (18F): Safety Population
Hide Arm/Group Description

Participants received 2 IV boluses of Flurpiridaz (18F) Injection in a large peripheral vein: 1 at rest then 1 during stress on the same day within 60 days prior to the ICA. Flurpiridaz (18F) Injection administered at rest and during stress conditions were not to exceed a total of 14 mCi (520 MBq) for an individual participant. Flurpiridaz was administered on Study Day 1.

SPECT agents 99mTc-based myocardial tracers, example [99mTc]tetrofosmin or [99mTc]sestamibi were administered as per American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location. For each participant, the same stress type (pharmacologic or exercise) was used for the SPECT and Flurpiridaz (18F) Injection PET MPI. Also, if pharmacological stress was used, the same agent and the same dose of pharmacological stress agent was used for both types of imaging for the same participant.

Pharmacological stress agents were administered according to the respective Package Insert (as applicable) or American Society of Nuclear Cardiology or European Association of Cardiovascular Imaging standards corresponding to study site location.
All-Cause Mortality
Flurpiridaz (18F): Safety Population
Affected / at Risk (%)
Total   1/604 (0.17%) 
Hide Serious Adverse Events
Flurpiridaz (18F): Safety Population
Affected / at Risk (%)
Total   20/604 (3.31%) 
Cardiac disorders   
Acute myocardial infarction † 1  2/604 (0.33%) 
Angina pectoris † 1  2/604 (0.33%) 
Angina unstable † 1  1/604 (0.17%) 
Atrial fibrillation † 1  1/604 (0.17%) 
Bradycardia † 1  1/604 (0.17%) 
Coronary artery perforation † 1  1/604 (0.17%) 
Left ventricular dysfunction † 1  1/604 (0.17%) 
Ventricular fibrillation † 1  1/604 (0.17%) 
Ventricular tachycardia † 1  1/604 (0.17%) 
General disorders   
Chest pain † 1  1/604 (0.17%) 
Vascular stent thrombosis † 1  1/604 (0.17%) 
Immune system disorders   
Anaphylactic shock † 1  1/604 (0.17%) 
Injury, poisoning and procedural complications   
Post procedural fever † 1  1/604 (0.17%) 
Investigations   
Electrocardiogram abnormal † 1  1/604 (0.17%) 
Respiratory, thoracic and mediastinal disorders   
Asthma † 1  1/604 (0.17%) 
Bronchospasm † 1  1/604 (0.17%) 
Skin and subcutaneous tissue disorders   
Urticaria chronic † 1  1/604 (0.17%) 
Vascular disorders   
Hypertensive crisis † 1  1/604 (0.17%) 
1
Term from vocabulary, MedDRA version 24.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Flurpiridaz (18F): Safety Population
Affected / at Risk (%)
Total   145/604 (24.01%) 
Cardiac disorders   
Angina pectoris † 1  32/604 (5.30%) 
Nervous system disorders   
Headache † 1  80/604 (13.25%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea † 1  68/604 (11.26%) 
1
Term from vocabulary, MedDRA version 24.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI and/or institution is that the Sponsor can review results communications prior to public release and can restrict communications regarding trial results for a period that is more than 30 days (publications/abstracts) but not to exceed 90 days (patent related issues) from the time submitted to the Sponsor to review. The PI may be asked to remove any Sponsor confidential information and/or delay publication to protect any proprietary information.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Francois Tranquart, M.D., Ph.D
Organization: GE HealthCare
Phone: 447775543206
EMail: francois.tranquart@ge.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: GE Healthcare
ClinicalTrials.gov Identifier: NCT03354273    
Other Study ID Numbers: GE-265-303
2017-005011-14 ( EudraCT Number )
First Submitted: November 21, 2017
First Posted: November 27, 2017
Results First Submitted: May 4, 2023
Results First Posted: July 12, 2023
Last Update Posted: July 12, 2023