Clinical trial NCT02959814: Diagnostic Accuracy of On-line Quantitative Flow Ratio (QFR). FAVOR II Europe-Japan
Official title: Diagnostic Accuracy of On-line Quantitative Flow Ratio. Functional Assessment by Virtual Online Reconstruction (The FAVOR II Europe-Japan Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Keywords: Fractional Flow Reserve
Quantitative Coronary Analysis
Stable coronary artery disease
Angina pectoris
Lead sponsor: Aarhus University Hospital Skejby
Sponsor class: OTHER
First posted: 2016-11-09
Enrollment: 329
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with stable angina pectoris admitted for coronary angiography due to high risk of significant coronary stenosis

Brief 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 1 hour
measure: 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)
timeFrame: 1 hour
Secondary outcomes:
measure: Percentage of Patients With Successful QFR in Patients With Successful FFR (Feasibility)
timeFrame: 1 hour
measure: Proportion of Patients With Positive QFR of FFR Positive Patients (True Positives) (Sensitivity)
timeFrame: 1 hour
measure: Proportion of Patients With Negative QFR of FFR Negative Patients (True Negatives) (Specificity)
timeFrame: 1 hour
measure: Proportion of Patients With Positive FFR (True Positives) of Patients With Positive QFR (Positive Predictive Value)
timeFrame: 1 hour
measure: Proportion of Patients With Negative FFR (True Negatives) of Patients With Negative QFR (Negative Predictive Value)
timeFrame: 1 hour
measure: Diagnostic Performance of QFR in Comparison to FFR Reported as Positive and Negative Likelihood Ratio
timeFrame: 1 hour
measure: Diagnostic Grey Zone Calculation. QFR Limits for Achieving 95% Sensitivity and Specificity in Comparison to FFR
timeFrame: 1 hour
measure: Diagnostic Accuracy of TIMI-flow Based QFR in Comparison to 2D QCA (>50% Diameter Stenosis)
timeFrame: 1 hour
measure: Participants With Myocardial Infarction (Number of Patients)
timeFrame: 1 day
measure: All-cause Mortality (Number of Patients)
timeFrame: 1 day
measure: Time to FFR
timeFrame: 1 hour
measure: Time to QFR After Receiving Angiographic Images
timeFrame: 1 hour
measure: Contrast Use
timeFrame: 1 hour
measure: Fluoroscopy Time
timeFrame: 1 hour
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Aarhus University Hspital
city: Massy
country: France
facility: Institut Cardiovasculaire Paris Sud Massy
city: Essen
country: Germany
facility: Elizabeth Krankenhaus Essen
city: Giessen
country: Germany
facility: Universitätsklinikum Gießen
city: Caserta
country: Italy
facility: Azienda ospedaliera Sant'Anna e S. sebastiano di Caserta
city: Ferrara
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara, University of Ferrara
city: Mestre
country: Italy
facility: Ospedale dell'Angelo di Mestre
city: Gifu
country: Japan
facility: Gifu Heart Center
city: The Hague
country: Netherlands
facility: HagaZiekenhuis
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
Study officials:
affiliation: Aarhus University Hospital, Denmark
name: Niels R. Holm, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 JHC, 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.
citation: Westra J, Andersen BK, Campo G, Matsuo H, Koltowski L, Eftekhari A, Liu T, Di Serafino L, Di Girolamo D, Escaned J, Nef H, Naber C, Barbierato M, Tu S, Neghabat O, Madsen M, Tebaldi M, Tanigaki T, Kochman J, Somi S, Esposito G, Mercone G, Mejia-Renteria H, Ronco F, Botker HE, Wijns W, Christiansen EH, Holm NR. Diagnostic Performance of In-Procedure Angiography-Derived Quantitative Flow Reserve Compared to Pressure-Derived Fractional Flow Reserve: The FAVOR II Europe-Japan Study. J Am Heart Assoc. 2018 Jul 6;7(14):e009603. doi: 10.1161/JAHA.118.009603.