FUnctional diagnoSIs of corONary Stenosis (FUSION)

Completed

Conditions: Coronary Artery Disease
Coronary Stenosis

Interventions: Procedure: ICA (Invasive Coronary Angiography)
Procedure: OCT
Procedure: FFR
Other: VFR Analysis

Registration Number: NCT04356027

Lead Sponsor: Abbott Medical Devices

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 312

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 Exclusion Criteria:

Artifact in pre-PCI OCT for the target lesion or in the event of multiple target lesions, artifact in pre-PCI OCT for ALL target lesions
Target lesion requires any preparation (including but not limited to balloon dilatation, atherectomy, etc.) prior to pre-PCI OCT and physiology measurement, or in case of multiple target lesions, ALL target lesions require-any preparation (including but not limited to balloon dilatation, atherectomy, etc.) prior to pre-PCI OCT and physiology measurement
Severe vessel tortuosity or calcification in the target vessel such that it is unlikely that the OCT catheter can be delivered
Target lesion not imaged by OCT or in the event of multiple target lesions, ALL target lesions not imaged by OCT
Pressure drift of > 0.03; i.e. Pd and Pa ratio value < 0.97 or > 1.03, unless physiology measurements are repeated after re-equalization
Target lesion or significant CAD beyond 60mm from coronary ostium; i.e. not able to clearly image and capture all disease segment with OCT in 1 run
Incorrectly done or unsuccessful catheter purge and/or contrast flush
Presence of plaque rupture and/or intravascular hematoma in target vessel (visual % diameter stenosis ≥ 40%)
Inability to receive intracoronary nitroglycerin prior to OCT or FFR
Use of flush media other than radiographic contrast

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Standard of Care: Angiography, OCT, FFR, and VFR	ICA (Invasive Coronary Angiography)	Patients will have Pre-OCT Angiography, OCT pullbacks, a FFR measurement and a VFR analysis
Standard of Care: Angiography, OCT, FFR, and VFR	OCT	Patients will have Pre-OCT Angiography, OCT pullbacks, a FFR measurement and a VFR analysis
Standard of Care: Angiography, OCT, FFR, and VFR	VFR Analysis	Patients will have Pre-OCT Angiography, OCT pullbacks, a FFR measurement and a VFR analysis
Standard of Care: Angiography, OCT, FFR, and VFR	FFR	Patients will have Pre-OCT Angiography, OCT pullbacks, a FFR measurement and a VFR analysis

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (28): HonorHealth
🇺🇸
Scottsdale, Arizona, United States
Arkansas Heart Hospital
🇺🇸
Little Rock, Arkansas, United States
The Cardiac & Vascular Institute Research Foundation, LLC
🇺🇸
Gainesville, Florida, United States
Holy Spirit Hospital
🇺🇸
Camp Hill, Pennsylvania, United States
Cardiovascular Research Institute of Kansas
🇺🇸
Wichita, Kansas, United States
New York University Hospital
🇺🇸
New York, New York, United States
New York-Presbyterian/Columbia University Medical Center
🇺🇸
New York, New York, United States
UCLA Medical Center Santa Monica
🇺🇸
Santa Monica, California, United States
Holy Cross Hospital
🇺🇸
Fort Lauderdale, Florida, United States
Atlanta VA Medical Center
🇺🇸
Decatur, Georgia, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
St. Patrick Hospital
🇺🇸
Missoula, Montana, United States
University of Texas Medical Branch (UTMB)
🇺🇸
Galveston, Texas, United States
Memorial Hermann Hospital
🇺🇸
Houston, Texas, United States
Heart Center Research, LLC.
🇺🇸
Huntsville, Alabama, United States
VA Palo Alto Medical Center
🇺🇸
Palo Alto, California, United States
Brigham & Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Montefiore Medical Center - Moses Division
🇺🇸
Bronx, New York, United States
Spartanburg Regional Medical Center
🇺🇸
Spartanburg, South Carolina, United States
Greenville Health System
🇺🇸
Greenville, South Carolina, United States
Via Christi Regional Medical Center - St. Francis Campus
🇺🇸
Wichita, Kansas, United States
Providence St. Vincent Medical Center
🇺🇸
Portland, Oregon, United States
VA Medical Center Durham
🇺🇸
Durham, North Carolina, United States
Austin Heart
🇺🇸
Austin, Texas, United States
St. Francis Hospital
🇺🇸
Roslyn, New York, United States
Tampa General Hospital
🇺🇸
Tampa, Florida, United States