Coronary Artery Disease, Coronary Stenosis
Conditions
Keywords
Virtual Flow Reserve (VFR), Optical Coherence Tomography (OCT), Fractional Flow Reserve (FFR), Percutaneous Coronary Intervention (PCI), OPTIS System, Dragonfly, PressureWire X
Brief summary
The purpose of the FUSION study is to validate the diagnostic performance of Virtual Flow Reserve (VFR) by comparing it against a reference standard, fractional flow reserve (FFR).
Detailed description
This study is a single-arm, prospective, multi-center study collecting OCT pullback images of lesions pre-percutaneous coronary intervention (PCI) and (optional) post-PCI procedure, and the corresponding pressure tracings and physiology indices. Up to 30 centers in the US will enroll approximately 310 patients. The expected duration of enrollment is approximately 15 months. The total duration of the clinical investigation is expected to be approximately 27 months.
Interventions
PROCEDUREICA (Invasive Coronary Angiography)
Patients will undergo a Pre-PCI Angiography
PROCEDUREOCT
OCT pullback images will be collected pre-PCI and (optional) post-PCI procedure
PROCEDUREFFR
FFR will be measured
OTHERVFR Analysis
VFR will be calculated offline using the OCT pullback images
Sponsors
Abbott Medical Devices
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Patient provides written informed consent * Scheduled for clinically indicated coronary catheterization with the intent to perform physiologic assessment to guide physician clinical course (in lesions with visual % diameter stenosis 40-90%), if clinically indicated * Subject is undergoing invasive FFR with Adenosine (high-dose intra-coronary (IC) \[200 μg for the left and or 100 μg for the right coronary artery\] or 140 μg/kg/min for intravenous (IV)) used as hyperemic stimulus * Clinical presentation with or history of stable angina, unstable angina, or silent ischemia (defined as abnormal stress test or abnormal invasive physiology assessment) that has led to the procedure General
Exclusion criteria
* Prior history of myocardial infarction (MI) in the target vessel * Presence of acute ST Elevation Myocardial Infarction (STEMI) * Culprit vessel of Non-ST Elevation Myocardial Infarction (NSTEMI) * TIMI flow \< Grade 3 at baseline or visible thrombus * Prior history of coronary artery bypass grafting (CABG) * Prior heart transplant * Severe valvular heart disease or history of valve repair or replacement * Prior history of PCI with stent in target vessel, or target vessel involves in-stent restenosis. * Target coronary vessel is supplied by major collaterals or is supplying major collaterals to a CTO (chronic total occlusion) * CTO in the target vessel * Severe diffuse disease observed in target vessel defined as the presence of diffuse, serial gross luminal irregularities present in the majority of the coronary tree * Presence of myocardial bridge (MB), regardless of vessel location * Contraindication for FFR examination or administration of vasodilators * Known LVEF ≤45% * Target lesion involves Left Main coronary artery or ostial right coronary artery * Known renal insufficiency (eGFR \< 30 ml/kg/m\^2 or serum creatinine ≥ 2.5 mg/dL) unless patient is on dialysis * Heart Failure NYHA Class III or IV * Subject is pregnant (For a female subject of childbearing potential, a pregnancy test must be performed within 14 days (≤14 days) prior to the index procedure per site standard test) * Subject has or had active COVID-19 symptoms and/or a positive test result within the prior 2 months * Participation in another clinical study of an investigational drug or device * Presence of aneurysm in the target vessel Imaging and Pressure Tracing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity and Specificity of Virtual Flow Reserve (VFR) Against Fractional Flow Reserve (FFR) | Baseline (pre-procedure) and immediately post-procedure | Sensitivity and specificity of the VFR compared with FFR each of which will be tested against a prespecified performance goal. FFR with a binary cut-off of 0.80 will be used as the reference standard for comparison. FFR or VFR value ≤ 0.80 will be considered positive (ischemia-causing), and FFR or VFR value \> 0.80 will be considered negative (non-ischemia-causing). Sensitivity is defined as the percentage of VFR positive lesions, in the group of FFR positive lesions. Sensitivity=TP/(TP+FN) x 100%, where TP denotes the number of True Positives (both VFR and FFR positive) and FN denotes the number of False Negatives (VFR negative but FFR positive). Specificity is defined as the percentage of VFR negative lesions in the group of FFR negative lesions. Specificity=TN/(TN+FP) x 100%, where TN denotes the number of True Negatives (both VFR and FFR negatives) and FP denotes the number of False Positives (VFR positive but FFR negative). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Diagnostic Accuracy | Baseline (pre-procedure) and immediately post-procedure | Overall diagnostic accuracy is defined as the proportion of correctly classified lesions among all lesions. Overall Diagnostic Accuracy= (TP+TN)/(TP+TN+FP+FN) x 100%, where TP denotes the number of True Positives, FN denotes the number of False Negatives, TN denotes the number of True Negatives, and FN denotes the number of False Negatives. |
| Positive Predictive Value (PPV) and Negative Predictive Value (NPV) | Baseline (pre-procedure) and immediately post-procedure | PPV is defined as the proportion of lesions with the disease and with a positive test result among the group of lesions with a positive test result. PPV= TP/(TP+FP) x 100%, where TP denotes the number of True Positives and FP denotes the number of False Positives. NPV is defined as the proportion of lesions without the disease and with a negative test result among the group of lesions with negative test results. NPV= TN/(TN+FN) x 100%, where TN denotes the number of True Negatives and FN denotes the number of False Negatives. |
| Correlation Between VFR and FFR | Baseline (pre-procedure) and immediately post-procedure (post-procedure) | The correlation between VFR and FFR will be estimated as the R\^2 correlation coefficient from the simple linear regression model using VFR value as the independent variable and FFR as the dependent variable. |
| Area Under Curve (AUC) Against FFR | Baseline (pre-procedure) and immediately post-procedure (post-procedure) | AUC will be estimated as the area under the ROC curve. ROC curve will be constructed using specificity on the x-axis and sensitivity on the y-axis. Sensitivity and specificity are calculated at various values of VFR and FFR, and the AUC curve will be drawn using logistic regression. |
Countries
United States
Participant flow
Recruitment details
The study enrolled a total of 312 subjects with a total of 315 vessels from 27 sites. After being reviewed for quality by the core laboratory, 224 pre-PCI and 42 post-PCI vessels from 224 subjects remained for the endpoints analysis.
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care: Angiography, OCT, FFR, and VFR This is a single arm study. Patients will have Pre-OCT Angiography, OCT pullbacks, a FFR measurement and a VFR analysis
ICA (Invasive Coronary Angiography): Patients will undergo a Pre-PCI Angiography
OCT: OCT pullback images will be collected pre-PCI and (optional) post-PCI procedure
FFR: FFR will be measured
VFR Analysis: VFR will be calculated offline using the OCT pullback images | 224 |
| Total | 224 |
Baseline characteristics
| Characteristic | Standard of Care: Angiography, OCT, FFR, and VFR |
|---|---|
| Age, Continuous | 67.4 years STANDARD_DEVIATION 9.2 |
| Hyperlipidemia | 186 participants |
| Hypertension | 182 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants |
| Race (NIH/OMB) White | 191 Participants |
| Region of Enrollment United States | 224 participants |
| Sex: Female, Male Female | 68 Participants |
| Sex: Female, Male Male | 156 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 312 |
| other Total, other adverse events | 3 / 312 |
| serious Total, serious adverse events | 5 / 312 |
Outcome results
Primary
Sensitivity and Specificity of Virtual Flow Reserve (VFR) Against Fractional Flow Reserve (FFR)
Sensitivity and specificity of the VFR compared with FFR each of which will be tested against a prespecified performance goal. FFR with a binary cut-off of 0.80 will be used as the reference standard for comparison. FFR or VFR value ≤ 0.80 will be considered positive (ischemia-causing), and FFR or VFR value \> 0.80 will be considered negative (non-ischemia-causing). Sensitivity is defined as the percentage of VFR positive lesions, in the group of FFR positive lesions. Sensitivity=TP/(TP+FN) x 100%, where TP denotes the number of True Positives (both VFR and FFR positive) and FN denotes the number of False Negatives (VFR negative but FFR positive). Specificity is defined as the percentage of VFR negative lesions in the group of FFR negative lesions. Specificity=TN/(TN+FP) x 100%, where TN denotes the number of True Negatives (both VFR and FFR negatives) and FP denotes the number of False Positives (VFR positive but FFR negative).
Time frame: Baseline (pre-procedure) and immediately post-procedure
Population: The primary analysis population included vessels in enrolled subjects having acceptable OCT pullbacks and pressure tracings for computing both the VFR and FFR indices. This is a single-arm study, so there is no data to report per arm, only data collected at different time points throughout the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care: Angiography, OCT, FFR, and VFR | Sensitivity and Specificity of Virtual Flow Reserve (VFR) Against Fractional Flow Reserve (FFR) | Sensitivity | 82 vessels |
| Standard of Care: Angiography, OCT, FFR, and VFR | Sensitivity and Specificity of Virtual Flow Reserve (VFR) Against Fractional Flow Reserve (FFR) | Specificity | 136 vessels |
Secondary
Area Under Curve (AUC) Against FFR
AUC will be estimated as the area under the ROC curve. ROC curve will be constructed using specificity on the x-axis and sensitivity on the y-axis. Sensitivity and specificity are calculated at various values of VFR and FFR, and the AUC curve will be drawn using logistic regression.
Time frame: Baseline (pre-procedure) and immediately post-procedure (post-procedure)
Population: The primary analysis population included vessels in enrolled subjects having acceptable OCT pullbacks and pressure tracings for computing both the VFR and FFR indices. This is a single-arm study, so there is no data to report per arm, only data collected at different time points throughout the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care: Angiography, OCT, FFR, and VFR | Area Under Curve (AUC) Against FFR | 0.8790 probability |
Secondary
Correlation Between VFR and FFR
The correlation between VFR and FFR will be estimated as the R\^2 correlation coefficient from the simple linear regression model using VFR value as the independent variable and FFR as the dependent variable.
Time frame: Baseline (pre-procedure) and immediately post-procedure (post-procedure)
Population: The primary analysis population included vessels in enrolled subjects having acceptable OCT pullbacks and pressure tracings for computing both the VFR and FFR indices. This is a single-arm study, so there is no data to report per arm, only data collected at different time points throughout the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care: Angiography, OCT, FFR, and VFR | Correlation Between VFR and FFR | 0.4992 correlation coefficient |
Secondary
Overall Diagnostic Accuracy
Overall diagnostic accuracy is defined as the proportion of correctly classified lesions among all lesions. Overall Diagnostic Accuracy= (TP+TN)/(TP+TN+FP+FN) x 100%, where TP denotes the number of True Positives, FN denotes the number of False Negatives, TN denotes the number of True Negatives, and FN denotes the number of False Negatives.
Time frame: Baseline (pre-procedure) and immediately post-procedure
Population: The primary analysis population included vessels in enrolled subjects having acceptable OCT pullbacks and pressure tracings for computing both the VFR and FFR indices. This is a single-arm study, so there is no data to report per arm, only data collected at different time points throughout the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care: Angiography, OCT, FFR, and VFR | Overall Diagnostic Accuracy | 218 vessels |
Secondary
Positive Predictive Value (PPV) and Negative Predictive Value (NPV)
PPV is defined as the proportion of lesions with the disease and with a positive test result among the group of lesions with a positive test result. PPV= TP/(TP+FP) x 100%, where TP denotes the number of True Positives and FP denotes the number of False Positives. NPV is defined as the proportion of lesions without the disease and with a negative test result among the group of lesions with negative test results. NPV= TN/(TN+FN) x 100%, where TN denotes the number of True Negatives and FN denotes the number of False Negatives.
Time frame: Baseline (pre-procedure) and immediately post-procedure
Population: The primary analysis population included vessels in enrolled subjects having acceptable OCT pullbacks and pressure tracings for computing both the VFR and FFR indices. This is a single-arm study, so there is no data to report per arm, only data collected at different time points throughout the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care: Angiography, OCT, FFR, and VFR | Positive Predictive Value (PPV) and Negative Predictive Value (NPV) | PPV number analyzed | 82 vessels |
| Standard of Care: Angiography, OCT, FFR, and VFR | Positive Predictive Value (PPV) and Negative Predictive Value (NPV) | NPV number analyzed | 136 vessels |