Diagnostic Accuracy of On-line Quantitative Flow Ratio (QFR). FAVOR II Europe-Japan

Coronary Artery Disease Clinical Trial

— FAVOR II EJ  

Official title:

Diagnostic Accuracy of On-line Quantitative Flow Ratio. Functional Assessment by Virtual Online Reconstruction (The FAVOR II Europe-Japan Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02959814
• Other study ID #: 1-10-72-219-16
• Status: Completed
• Start date: February 22, 2017
• Est. completion date: June 1, 2018

Study information

• Verified date: December 2019
• Source: Aarhus University Hospital Skejby
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Quantitative Flow Ratio (QFR) is a novel method for evaluating the functional significance of coronary stenosis. QFR is assessed by calculation of the pressure in the vessel based on two angiographic projections. The purpose of the FAVOR II study is to evaluate the diagnostic accuracy of on-line QFR compared to 2D Quantitative Coronary Angiography (QCA) with FFR as gold standard.

Description:

Background:

Patients at high risk of having one or more coronary stenosis are evaluated routinely by invasive coronary angiography (CAG). Lesions are often quantified by QCA, but fractional flow reserve is increasingly used to assess functional significance of identified stenosis. FFR is assessed during CAG by advancing a wire with a pressure transducer towards the stenosis and measure the ratio in pressure between the two sides of the stenosis during medical induced maximum blood flow (hyperaemia).

The solid evidence for FFR evaluation of coronary stenosis and the relative simplicity in performing the measurements have supported adoption of an FFR based strategy in many centers but the need for interrogating the stenosis by a pressure wire, the cost of the wire, and the drug inducing hyperaemia limits more widespread adoption.

Quantitative Flow Ratio is a novel method for evaluating the functional significance of coronary stenosis by calculation of the pressure drop in the vessel based on two angiographic projections.

The FAVOR I study (Tu et al.), showed promising results for core laboratory QFR analysis in selected patients.

The purpose of the FAVOR II study is to evaluate the feasibility and diagnostic precision of in-procedure QFR during CAG in comparison to QCA with FFR as gold standard for physiological lesion evaluation.

Hypothesis: QFR has superior sensitivity and specificity for detection of functional significant lesions in comparison to QCA with FFR as gold standard

Methods: Prospective, observational, multicenter study with inclusion of 310 patients.

Patients with indication for FFR are enrolled. At least two angiographic projections are acquired during resting conditions. QFR is calculated in-procedure using the Medis Suite application and simultaneously to the operator performing the FFR measurement. The QFR observer is blinded to the FFR measurement.

QFR is reassessed off-line by the Interventional Coronary Imaging Core Laboratory, Aarhus University, Denmark, blinded to FFR and in-procedure QFR results.

FFR is assessed by core laboratory reading, blinded to QFR results. All data are entered and stored in a protected and logged trial management system (TrialPartner, Aarhus University, Denmark).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 329
• Est. completion date: June 1, 2018
• Est. primary completion date: October 17, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Stable angina pectoris or secondary evaluation of stenosis after acute MI

• Age > 18 years

• Able to provide signed informed consent

• Angiographic inclusion criteria:

• Indication for FFR in at least one stenosis:

• Diameter stenosis of 30%-90% by visual estimate

• Reference vessel size > 2 mm in stenotic segment by visual estimate

Exclusion Criteria:

• Myocardial infarction within 72 hours

• Severe asthma or severe chronic obstructive pulmonary disease

• Severe heart failure (NYHA=III)

• S-creatinine>150µmol/L or GFR<45 ml/kg/1.73m2

• Allergy to contrast media or adenosine

• Atrial fibrillation

• Angiographic exclusion criteria:

Lesion specific

• Below 30% and above 90% diameter stenosis by visual estimate.

• Reference size of vessel below 2 mm by visual estimation.

• Ostial LMCA lesions

• Ostial RCA lesions

• Distal LMCA lesions in combination with proximal Cx lesions

• Other bifurcation stenosis with lesions on both sides of a major shift (>1mm) in reference diameter Angiographic quality

• Poor image quality precluding contour detection

• Good contrast filling not possible

• Severe overlap of stenosed segments

• Severe tortuosity of target vessel

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Other:
• QFR (observational)
QFR assessment by Medis Suite, Medis medical imaging B.V., The Netherlands

Locations

Country	Name	City	State
Denmark	Aarhus University Hspital	Aarhus N
France	Institut Cardiovasculaire Paris Sud Massy	Massy
Germany	Elizabeth Krankenhaus Essen	Essen
Germany	Universitätsklinikum Gießen	Giessen
Italy	Azienda ospedaliera Sant'Anna e S. sebastiano di Caserta	Caserta
Italy	Azienda Ospedaliero-Universitaria di Ferrara, University of Ferrara	Ferrara
Italy	Ospedale dell'Angelo di Mestre	Mestre
Japan	Gifu Heart Center	Gifu
Netherlands	HagaZiekenhuis	The Hague
United Kingdom	Golden Jubilee National Hospital	Glasgow

Sponsors (1)

Lead Sponsor	Collaborator
Aarhus University Hospital Skejby

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Italy,  Japan,  Netherlands,  United Kingdom, 

References & Publications (1)

Tu S, Westra J, Yang J, von Birgelen C, Ferrara A, Pellicano M, Nef H, Tebaldi M, Murasato Y, Lansky A, Barbato E, van der Heijden LC, Reiber JH, Holm NR, Wijns W; FAVOR Pilot Trial Study Group. Diagnostic Accuracy of Fast Computational Approaches to Derive Fractional Flow Reserve From Diagnostic Coronary Angiography: The International Multicenter FAVOR Pilot Study. JACC Cardiovasc Interv. 2016 Oct 10;9(19):2024-2035. doi: 10.1016/j.jcin.2016.07.013. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity: Proportion of Patients With Positive QFR of FFR Positive Patients (True Positives) Compared to Proportion of Patients With Positive Percentual Diameter Stenosis (DS%) Assessed by 2D QCA of FFR Positive Patients (True Positives)	Positive FFR is defined as FFR=0.80. Positive QFR is defined as QFR=0.80. Positive DS% is defined as DS% > 50%	1 hour
Primary	Specificity: Proportion of Patients With Negative QFR of FFR Negative Patients (True Negatives) Compared to Proportion of Patients With Negative DS% Assessed by 2D QCA of FFR Negative Patients (True Negatives)	Negative FFR is defined as FFR>0.80. Negative QFR is defined as QFR>0.80. Negative DS% is defined as DS% = 50%.	1 hour
Secondary	Percentage of Patients With Successful QFR in Patients With Successful FFR (Feasibility)		1 hour
Secondary	Proportion of Patients With Positive QFR of FFR Positive Patients (True Positives) (Sensitivity)	Positive FFR is defined as FFR=0.80. Positive QFR is defined as QFR=0.80	1 hour
Secondary	Proportion of Patients With Negative QFR of FFR Negative Patients (True Negatives) (Specificity)	Negative FFR is defined as FFR>0.80. Negative QFR is defined as QFR>0.80	1 hour
Secondary	Proportion of Patients With Positive FFR (True Positives) of Patients With Positive QFR (Positive Predictive Value)	Positive FFR is defined as FFR=0.80. Positive QFR is defined as QFR=0.80	1 hour
Secondary	Proportion of Patients With Negative FFR (True Negatives) of Patients With Negative QFR (Negative Predictive Value)	Negative FFR is defined as FFR>0.80. Negative QFR is defined as QFR>0.80	1 hour
Secondary	Diagnostic Performance of QFR in Comparison to FFR Reported as Positive and Negative Likelihood Ratio	Positive likelihood ratio is defined as sensitivity/(1-specificity). Negative likelihood ratio is defined as (1-sensitivty)/specificity	1 hour
Secondary	Diagnostic Grey Zone Calculation. QFR Limits for Achieving 95% Sensitivity and Specificity in Comparison to FFR	QFR limits to yield 95% sensitivity and specificity. The QFR limits are identified by Area under the receiver operating curve analysis.; QFR limits are defined as the numerical QFR ratios (0-1.00).	1 hour
Secondary	Diagnostic Accuracy of TIMI-flow Based QFR in Comparison to 2D QCA (>50% Diameter Stenosis)	Comparison of proportion of participants correctly classified by QFR and 2D QCA using FFR as reference standard.; Diagnostic accuracy is defined as (true positives + false negatives) / (true positives+false positives+true negatives+false negatives).; Positive FFR is defined as FFR=0.80. Positive QFR is defined as QFR=0.80. Negative FFR is defines as FFR>0.80. Negative QFR is defines as QFR>0.80. Positive 2D QCA is defined as 2D-QCA % percent diameter stenosis >50. Negative 2D QCA is defined as 2D-QCA % diameter stenosis=50.	1 hour
Secondary	Participants With Myocardial Infarction (Number of Patients)	Peri-procedural myocardial infarction	1 day
Secondary	All-cause Mortality (Number of Patients)	Peri-procedural mortality	1 day
Secondary	Time to FFR	Time from starting preparations to do FFR (e.g. ordering assistants to prepare pressure wire, adenosine infusion etc.) to FFR value is obtained and drift has been verified to be within the prespecified limits	1 hour
Secondary	Time to QFR After Receiving Angiographic Images	Time from first image evaluation on QFR computer until TIMI frame count based QFR value is obtained	1 hour
Secondary	Contrast Use	Volume of contrast for total procedure	1 hour
Secondary	Fluoroscopy Time	Fluoroscopy time for total procedure	1 hour