Novel Adenosine-independent Index of Coronary Artery Stenosis Severity Resting Flow Reserve (RFR)

Derivation and Validation of a Novel Adenosine-independent Index of Coronary Artery Stenosis Severity Resting Flow Reserve

This study will enroll patients who are referred for coronary angiography and require physiological assessment to see if the lesion can be treated as per the local standard of care. Approximately 92 participants will be enrolled. There are no follow up visits required so participation in this study will end when subjects are discharged from the hospital.The study will be comparing the resting flow reserve against the instantaneous wave-free ratio (iFR) and fractional flow reserve. All these tests offer a way to image a legion and determine if it is suitable to be treated. FFR measures the pressure differences across (narrowed coronary arteries usually due to atherosclerosis), iFR's are performed during cardiac catheterisation (angiography) using invasive coronary pressure wires which are placed in the arteries of the heart that are to be assessed and the Resting flow reserve looks at the maximum increase in blood flow through the coronary arteries above the normal resting volume.

Study Overview

• Status: Terminated
• Conditions: Coronary; Ischemic
• Intervention / Treatment: Device: Volcano Verrata Pressure Wire; Device: St. Jude Medical (SJM) Aeris Pressure Wire System

Detailed Description

Fractional flow reserve (FFR) measurement by under hyperemic conditions has become the invasive gold standard for determining the physiologic extent of cardiac ischemia, and which has been validated in several clinical outcomes studies as a way of optimizing case selection for percutaneous coronary intervention (PCI). More recently in two large-scale randomized controlled trials using a non-hyperemic resting measurement, the instantaneous wave free ratio (iFR) showed non-inferiority in major adverse cardiovascular events (MACE) comparing iFR to FFR for physiological assessment of moderate coronary stenosis. FFR is calculated as the ratio of the distal coronary pressure to the aortic pressure (Pd/Pa) during maximal micro-circulatory relaxation. iFR is a diagnostic tool used to assess whether a stenosis is causing a limitation of blood flow in coronary arteries with subsequent ischemia. iFR is performed during cardiac catheterization (angiography) using invasive coronary pressure wires which are placed in the coronary arteries that are to be assessed. The iFR negates the time averaging and administration of vasodilators necessary for FFR by identifying from the resting pressure waveform a period when the native microcirculatory resistance is constant and minimized in diastole. The study is looking at the accuracy and precision of a novel adenosine-independent index of coronary artery stenosis, the resting flow reserve, against the instantaneous wave-free ratio and fractional flow reserve.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Patient provides signed written informed consent before any study-specific procedure.
3. Undergoing coronary angiography, for silent ischemia, stable angina, acute coronary syndrome, or other acceptable indication per the local standard of care.
4. Angiographically 40%-90% stenosis present in at least one native coronary artery.
5. Undergoing physiological assessment for standard clinical or diagnostic indications

Exclusion Criteria:

1. Aorto-ostial lesion location within 3 mm of the aorta junction (both right and left).
2. Left main stenosis
3. Vessel(s) and lesion(s) not amenable for percutaneous coronary intervention (PCI) , for example diffuse disease.
4. Saphenous vein graft, chronic total occlusion
5. Haemodynamic instability at the time of intervention (heart rate<50 beats per minute, systolic blood pressure <90mmHg), balloon pump
6. Currently participating in another clinical study that interferes with study results.
7. Pregnant or nursing subjects and those who plan pregnancy in the period up to 1 year following index procedure.
8. Any other medical condition that in the opinion of the investigator will interfere with patient safety or study results.
9. High degree A-V block, sinus node disease.
10. Asthma/Chronic obstructive pulmonary disease (COPD) with active wheeze
11. Known hypersensitivity to adenosine
12. ST-Elevation Myocardial Infarction (STEMI) within 48 hours.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Primary; All patients who are referred for coronary angiography and require physiological assessment of intermediate lesions will have both RFR and iFR measured during their standard of care procedure. Both the RFR wire (St. Jude Medical (SJM) Aeris Pressure Wire System) and iFR (Volcano Verrata Pressure Wire) wire will be advanced across the lesion with the sensor located at least 3 cm distal from the lesion.

Device: Volcano Verrata Pressure Wire; Steerable guidewire with a pressure transducer mounted 3cm proximal to the tip. The guidewire has a diameter of 0.014". and is packaged preconnected to the connector with a torque device to facilitate navigation through the vasculature.; Other Names: iFR Wire; Device: St. Jude Medical (SJM) Aeris Pressure Wire System; The pressure wire is a 0.014'' guidewire with a pressure and temperature sensor integrated into the tip to enable measurements of physiological parameters.; Other Names: RFR Wire

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Agreement Between Mean RFR and iFR Measurements	Mean RFR measurements will be compared against mean iFR measurements to determine if there is an agreement between RFR and iFR for detection of ischemia.	During procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lesion Classification (FFR≤/>0.80) by RFR		During procedure
Lesion Classification (FFR≤/>0.80) by iFR		During procedure
Pressure Drift of RFR		During procedure
Pressure Drift of iFR		During procedure
Measurement Reproducibility for RFR	Reproducibility of RFR will be tested against iFR. Reproducibility will be measured by comparing the measure of RFR (minimal ratio of distal coronary pressure/aortic pressure) at time point 1 versus time point 2 against iFR (minimal ratio of distal coronary pressure/aortic pressure during the wave-free period of diastole) at time point 1 versus time point 2.	During procedure
Measurement Reproducibility for iFR	Reproducibility of iFR will be tested against RFR. Reproducibility will be measured by comparing the measure of iFR (minimal ratio of distal coronary pressure/aortic pressure during the wave-free period of diastole) at time point 1 versus time point 2 against RFR (minimal ratio of distal coronary pressure/aortic pressure) at time point 1 versus time point 2.	During procedure
Ability to Advance to the Target Lesion and Measure RFR and iFR	Percentage of technical failure due to the inability to deliver the wire and measure out of total number of all procedures	During procedure

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Ajay Kirtane, MD, CUMC

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2017
• Primary Completion (Actual): August 2, 2018
• Study Completion (Actual): August 2, 2018

Study Registration Dates

• First Submitted: February 22, 2018
• First Submitted That Met QC Criteria: March 5, 2018
• First Posted (Actual): March 12, 2018

Study Record Updates

• Last Update Posted (Actual): February 7, 2020
• Last Update Submitted That Met QC Criteria: January 28, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Stenosis; Coronary Artery Stenosis; Resting Flow Reserve (RFR); Volcano Verrata Pressure Wire
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Coronary Disease; Constriction, Pathologic; Coronary Stenosis
• Other Study ID Numbers: AAAR4732

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No