Functional Assessment by Virtual Online Reconstruction. The FAVOR III Europe Japan Study

Coronary Artery Disease Clinical Trial

— FAVOR III EJ  

Official title:

Comparison of Quantitative Flow Ratio (QFR) and Conventional Pressure-wire Based Functional Evaluation for Guiding Coronary Intervention. A Randomized Clinical Non-inferiority Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03729739
• Other study ID #: 1-10-72-263-18
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 6, 2018
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: Aarhus University Hospital Skejby
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Quantitative Flow Ratio (QFR) is a novel method for evaluating the functional significance of coronary stenosis. QFR is estimated based on two angiographic projections. Studies have shown a good correlation with the present wire-based standard approach Fractional Flow Reserve (FFR) for assessment of intermediate coronary stenosis. The purpose of the FAVOR III Europe Japan study is to investigate if a QFR-based diagnostic strategy will results in non-inferior clinical outcome after 12 months compared to a standard pressure-wire guided strategy in evaluation of patients with chest pain (stable angina pectoris) and intermediate coronary stenosis.

Description:

Patients at high risk of having one or more coronary stenosis are evaluated routinely by invasive coronary angiography (CAG). Lesions are often quantified by visual assessment of the angiogram, but physiological assessment of the functional significance by fractional flow reserve has been shown to improve clinical outcome, to reduce number of stents implanted, and has obtained the highest recommendation in European guidelines. 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 but the need for interrogating the stenosis by a pressure wire, the small risks associated hereto, the cost of the wire, and the drug inducing hyperaemia has limited 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 computation of two angiographic projections.

Two multi-center studies, the FAVOR II Europe-Japan and China studies evaluated the feasibility and diagnostic performance of in-procedure QFR, showing very good agreement between QFR and FFR.

The purpose of the FAVOR III Europe Japan study is to investigate if a QFR-based diagnostic strategy yields non-inferior 12-month clinical outcome compared to a standard pressure-wire guided strategy in evaluation of patients with stable angina pectoris and intermediate coronary stenosis.

Primary hypothesis: A QFR based diagnostic strategy results in non-inferior clinical outcome, assessed by a composite endpoint of all cause death, non-fatal myocardial infarction (MI) and unplanned revascularization after one year, compared to a strategy of pressure wire-based FFR for assessment of physiological significance of intermediate coronary artery stenosis.

Methods: Investigator initiated, 1:1 randomized, prospective, clinical outcome, non-inferiority, multi-center trial performed at up to 40 international sites with inclusion of 2000 patients.

Patients with stable angina pectoris or need for evaluation of non-culprit lesions after acute MI are enrolled. At least two angiographic projections are acquired during resting conditions. If the angiographic criteria are met, the patient is randomized to either a QFR- or an FFR-based diagnostic strategy.

Revascularization is performed according to best standard by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).

Patient follow-up is continued until 24 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2001
• Est. completion date: December 31, 2025
• Est. primary completion date: July 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age of 18 years and above

• Both genders

• Indication for invasive coronary angiography

• Patients with stable angina pectoris, or assessment of secondary lesions in stabilized non-STEMI patients or assessment of secondary lesions in patients with prior STEMI and staged evaluation of secondary lesions.

• Able to provide written informed consent

Angiographic inclusion criteria

• Diameter stenosis of 40-90% diameter stenosis

• Vessel diameter of at least 2.5 mm and supplying viable myocardium

• Patients with restenosis in a native coronary artery can be included

Exclusion Criteria:

• Severely impaired renal function: Glomerular filtration rate (GFR) < 20 mL/min/1.73m²

• Life expectancy less than one year

• Cardiogenic shock or unstable haemodynamic state (Killip class III and IV)

• ST-elevation myocardial infarction (STEMI) within 24 hours

• Bypass graft to any target vessel

• Atrial fibrillation at the time of the procedure

• Chronic total occlusions of any vessel with possible or established indication for treatment

• Pregnancy or intention to become pregnant during the course of the trial

• Breast feeding

• Planned need for concomitant valvular or aortic surgery

• Left ventricular ejection fraction (LVEF) < 30%

• Previous inclusion in the FAVOR III trial

• Enrolled in another clinical study, and for this reason not treated according to present European Society of Cardiology guidelines, or the protocol treatment conflicts with the protocol treatment of FAVOR III

• Inability to tolerate contrast media

• Inability to tolerate Adenosine

Angiographic exclusion criteria

• Ostial right coronary artery > 50% diameter stenosis

• Left main coronary artery > 50% diameter stenosis

• Lesions properties indicative of myocardial bridging

• Bifurcation lesions with major (>1 mm) step down in reference size across the bifurcation

• Severe tortuosity of any target vessel

• Severe overlap in the stenosed segment

• Poor image quality precluding identification of vessel contours

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Diagnostic Test:
• QFR-based diagnostic strategy
Novel computer based calculation of lesion severity. Pressure wire-free and adenosine-free
• FFR-based diagnostic strategy
Standard FFR based diagnostic method. Pressure drop across the stenosis is measured with a pressure wire during medical induced hyperaemic conditions

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus N
Denmark	Gentofte Hospital	Hellerup
France	GCS ES Axium - Parc Rambot	Aix-en-Provence
France	CHU de Lille, Lille University Hospital	Lille
France	Institut Cardiovasculaire Paris Sud (ICPS), Hopital Jacques Cartier	Massy
France	Hopital Haut-Leveque, Pessac	Pessac
France	Hôpital Privé Claude Galien	Quincy
France	Institut Arnault Tzanck	Saint-Laurent-du-Var	Nice
France	Clinique Pasteur, Toulouse	Toulouse
Germany	Charite-Universitatsmedizin Berlin	Berlin
Germany	Elisabeth Krankenhaus	Essen
Germany	University Clinic Leipzig	Leipzig
Italy	Ospedale Maggiore, AUSL Bologna	Bologna
Italy	Azienda Ospedaliero-Universitaria di Ferrara, University of Ferrara	Ferrara
Italy	Azienda Ospedaliero Universitaria Federico II di Napoli	Naples
Italy	San Luigi Gonzaga University Hospital, Turin	Orbassano
Italy	Arcispedale S. Maria Nuova di Reggio Emilia	Reggio Emilia
Italy	Ospedale degli Infermi di Rimini	Rimini
Italy	Ospedale di Rivoli, Torino	Torino
Italy	Azienda Ospedaliera Universitaria integrata Verona	Verona
Latvia	Riga Stradini University Hospital	Riga
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno Klinikos	Kaunas
Netherlands	Academic Medical Center (AMC)	Amsterdam
Netherlands	VU University Medical Center	Amsterdam
Netherlands	HagaZiekenhuis	The Hague
Poland	Medical University of Warsaw	Warsaw
Spain	Hospital Clinico de Coruña	Coruña
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital Lucus Agusti LUGO	Lugo
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Clinico Universitario de Valladolid	Valladolid
Spain	Hospital Álvaro Cunqueiro	Vigo
Sweden	Sahlgrenska University Hospital	Göteborg
Switzerland	Barbera Stähli	Zürich	Zûrich

Sponsors (2)

Lead Sponsor	Collaborator
Aarhus University Hospital Skejby	Medis Medical Imaging Systems

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Italy,  Latvia,  Lithuania,  Netherlands,  Poland,  Spain,  Sweden,  Switzerland, 

References & Publications (4)

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. — View 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. — View Citation

Westra J, Tu S, Winther S, Nissen L, Vestergaard MB, Andersen BK, Holck EN, Fox Maule C, Johansen JK, Andreasen LN, Simonsen JK, Zhang Y, Kristensen SD, Maeng M, Kaltoft A, Terkelsen CJ, Krusell LR, Jakobsen L, Reiber JHC, Lassen JF, Bottcher M, Botker HE, Christiansen EH, Holm NR. Evaluation of Coronary Artery Stenosis by Quantitative Flow Ratio During Invasive Coronary Angiography: The WIFI II Study (Wire-Free Functional Imaging II). Circ Cardiovasc Imaging. 2018 Mar;11(3):e007107. doi: 10.1161/CIRCIMAGING.117.007107. — View Citation

Xu B, Tu S, Qiao S, Qu X, Chen Y, Yang J, Guo L, Sun Z, Li Z, Tian F, Fang W, Chen J, Li W, Guan C, Holm NR, Wijns W, Hu S. Diagnostic Accuracy of Angiography-Based Quantitative Flow Ratio Measurements for Online Assessment of Coronary Stenosis. J Am Coll Cardiol. 2017 Dec 26;70(25):3077-3087. doi: 10.1016/j.jacc.2017.10.035. Epub 2017 Oct 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient oriented composite endpoint (PoCE)	A composite endpoint of 1) all-cause mortality, 2) any myocardial infarction, and 3) any unplanned revascularization	12 months
Secondary	Target vessel failure	A composite of cardiac death, target vessel myocardial infarction and ischemic driven target vessel revascularization.	1 month
Secondary	Target vessel failure	A composite of cardiac death, target vessel myocardial infarction and ischemic driven target vessel revascularization.	12 months
Secondary	Target vessel failure	A composite of cardiac death, target vessel myocardial infarction and ischemic driven target vessel revascularization.	24 months
Secondary	All-cause mortality	Total death includes cardiac death and other fatal categories such as cerebrovascular death, death from other cardiovascular disease (i.e. pulmonary embolism, dissection aortic aneurism will be included in this category), death from malignant disease, death from suicide, violence or accident, or death from other reasons.	1 month
Secondary	All-cause mortality	Total death includes cardiac death and other fatal categories such as cerebrovascular death, death from other cardiovascular disease (i.e. pulmonary embolism, dissection aortic aneurism will be included in this category), death from malignant disease, death from suicide, violence or accident, or death from other reasons.	12 months
Secondary	All-cause mortality	Total death includes cardiac death and other fatal categories such as cerebrovascular death, death from other cardiovascular disease (i.e. pulmonary embolism, dissection aortic aneurism will be included in this category), death from malignant disease, death from suicide, violence or accident, or death from other reasons.	24 months
Secondary	Cardiac death	Encompasses death due to coronary heart disease including fatal myocardial infarction, sudden cardiac death including fatal arrhythmias and cardiac arrest without successful resuscitation, death from heart failure including cardiogenic shock, and death related the cardiac procedure within 28 days from the procedure. If death is not clearly attributable to other non-cardiac causes it is adjudicated as cardiac death	1 month
Secondary	Cardiac death	Encompasses death due to coronary heart disease including fatal myocardial infarction, sudden cardiac death including fatal arrhythmias and cardiac arrest without successful resuscitation, death from heart failure including cardiogenic shock, and death related the cardiac procedure within 28 days from the procedure. If death is not clearly attributable to other non-cardiac causes it is adjudicated as cardiac death	12 months
Secondary	Cardiac death	Encompasses death due to coronary heart disease including fatal myocardial infarction, sudden cardiac death including fatal arrhythmias and cardiac arrest without successful resuscitation, death from heart failure including cardiogenic shock, and death related the cardiac procedure within 28 days from the procedure. If death is not clearly attributable to other non-cardiac causes it is adjudicated as cardiac death	24 months
Secondary	Myocardial infarction	Procedure and non-procedure related myocardial infarction. Protocol defined.	1 month
Secondary	Myocardial infarction	Procedure and non-procedure related myocardial infarction. Protocol defined.	12 months
Secondary	Myocardial infarction	Procedure and non-procedure related myocardial infarction. Protocol defined.	24 months
Secondary	Target vessel myocardial infarction	As "any myocardial infarction", but with culprit lesion in index vessel.	1 month
Secondary	Target vessel myocardial infarction	As "any myocardial infarction", but with culprit lesion in index vessel.	12 months
Secondary	Target vessel myocardial infarction	As "any myocardial infarction", but with culprit lesion in index vessel.	24 months
Secondary	Any unplanned revascularization	Coronary artery bypass grafting (CABG) or PCI of any lesion.; Planned Revascularization: Revascularization is considered planned when it is decided at the time of the index procedure, based on the results of angiography and functional testing. Planned revascularization could be performed at the time of the index procedure or within 60 days. Such revascularization is considered as "primary" revascularization and is not considered as an endpoint. The "planned" status of the revascularization is adjudicated.; Unplanned Revascularization: Revascularization is considered "unplanned" when not performed as part of standard care during the index procedure or if it is not planned as a staged procedure to occur within 60 days.	1 month
Secondary	Any unplanned revascularization	Coronary artery bypass grafting (CABG) or PCI of any lesion.; Planned Revascularization: Revascularization is considered planned when it is decided at the time of the index procedure, based on the results of angiography and functional testing. Planned revascularization could be performed at the time of the index procedure or within 60 days. Such revascularization is considered as "primary" revascularization and is not considered as an endpoint. The "planned" status of the revascularization is adjudicated.; Unplanned Revascularization: Revascularization is considered "unplanned" when not performed as part of standard care during the index procedure or if it is not planned as a staged procedure to occur within 60 days.	12 months
Secondary	Any unplanned revascularization	Coronary artery bypass grafting (CABG) or PCI of any lesion.; Planned Revascularization: Revascularization is considered planned when it is decided at the time of the index procedure, based on the results of angiography and functional testing. Planned revascularization could be performed at the time of the index procedure or within 60 days. Such revascularization is considered as "primary" revascularization and is not considered as an endpoint. The "planned" status of the revascularization is adjudicated.; Unplanned Revascularization: Revascularization is considered "unplanned" when not performed as part of standard care during the index procedure or if it is not planned as a staged procedure to occur within 60 days.	24 months
Secondary	Any ischemia driven de novo revascularization	Coronary artery bypass grafting or PCI of a vessel that was not evaluated nor treated during the index procedure. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI	1 month
Secondary	Any ischemia driven de novo revascularization	Coronary artery bypass grafting or PCI of a vessel that was not evaluated nor treated during the index procedure. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI	12 months
Secondary	Any ischemia driven de novo revascularization	Coronary artery bypass grafting or PCI of a vessel that was not evaluated nor treated during the index procedure. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI	24 months
Secondary	Ischemia driven target vessel revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel with documented ischemia. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI	1 month
Secondary	Ischemia driven target vessel revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel with documented ischemia. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI	12 months
Secondary	Ischemia driven target vessel revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel with documented ischemia. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI	24 months
Secondary	Ischemia driven treated target lesion revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel with documented ischemia that was treated during index or planned staged procedure. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI	1 month
Secondary	Ischemia driven treated target lesion revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel with documented ischemia that was treated during index or planned staged procedure. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI	12 months
Secondary	Ischemia driven treated target lesion revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel with documented ischemia that was treated during index or planned staged procedure. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI	24 months
Secondary	Ischemia driven, measured segment revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel that was evaluated by either FFR or QFR but not treated. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI.	1 month
Secondary	Ischemia driven, measured segment revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel that was evaluated by either FFR or QFR (both treated and not treated). In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI.	12 months
Secondary	Ischemia driven, measured segment revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel that was evaluated by either FFR or QFR but not treated. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI.	24 months
Secondary	Ischemia driven measured segment de novo revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel that was evaluated by either FFR or QFR but not treated. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI.	1 month
Secondary	Ischemia driven measured segment de novo revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel that was evaluated by either FFR or QFR but not treated. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI.	12 months
Secondary	Ischemia driven measured segment de novo revascularization	Coronary artery bypass grafting (CABG) or PCI of a study vessel that was evaluated by either FFR or QFR but not treated. In stable patients, ischemia should always be documented, using for example FFR, SPECT scan or MRI.	24 months
Secondary	Feasibility of QFR	Percentage of successful QFR in patients allocated to a QFR based diagnostic strategy	1 hour
Secondary	Feasibility of FFR	Percentage of successfully performed FFR measurements in vessels with attempted FFR (vessel level) Percentages of patients with successful FFR measurements (all attempted)	1 hour
Secondary	Number of lesion interrogated	Total number of lesions diagnosed with either QFR or FFR during the procedure	1 hour
Secondary	Procedure time	Time from introduction of the sheet until the sheet for coronary access is removed from the patient	1 hour
Secondary	Contrast volume	Total volume of contrast used in the procedure	1 hour
Secondary	Fluoroscopy time	Total fluoroscopy time for the procedure	1 hour
Secondary	Number of stents implanted	Total number of stents implanted during the procedure. Stents implanted in a staged procedure are included	1 hour