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

Sponsor

Aarhus University Hospital Skejby (Other)

Overall Status

Recruiting

CT.gov ID

NCT03729739

Collaborator

Medis Medical Imaging Systems (Other)

2,000

Enrollment

Locations

Arms

85.8

Anticipated Duration (Months)

46.5

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Diagnostic Test: QFR-based diagnostic strategy Diagnostic Test: FFR-based diagnostic strategy	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized clinical non-inferiority trialRandomized clinical non-inferiority trial

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Diagnostic

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

Actual Study Start Date :

Nov 6, 2018

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QFR-based diagnostic strategy Intermediate stenosis with indication for evaluation are diagnosed by Quantitative flow ratio (QFR). Revascularization is indicated if QFR≤0.80. Treatment is performed according to standard clinical practice.	Diagnostic Test: QFR-based diagnostic strategy Novel computer based calculation of lesion severity. Pressure wire-free and adenosine-free
Active Comparator: FFR-based diagnostic strategy Intermediate stenosis with indication for evaluation are diagnosed by fractional flow reserve (FFR). Revascularization is indicated if FFR≤0.80. Treatment is performed according to standard clinical practice.	Diagnostic Test: 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

Arm

Intervention/Treatment

Experimental: QFR-based diagnostic strategy

Intermediate stenosis with indication for evaluation are diagnosed by Quantitative flow ratio (QFR). Revascularization is indicated if QFR≤0.80. Treatment is performed according to standard clinical practice.

Diagnostic Test: QFR-based diagnostic strategy

Novel computer based calculation of lesion severity. Pressure wire-free and adenosine-free

Active Comparator: FFR-based diagnostic strategy

Intermediate stenosis with indication for evaluation are diagnosed by fractional flow reserve (FFR). Revascularization is indicated if FFR≤0.80. Treatment is performed according to standard clinical practice.

Diagnostic Test: 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

Outcome Measures

Primary Outcome Measures

Patient oriented composite endpoint (PoCE) [12 months]
A composite endpoint of 1) all-cause mortality, 2) any myocardial infarction, and 3) any unplanned revascularization

Secondary Outcome Measures

Target vessel failure [1 month]
A composite of cardiac death, target vessel myocardial infarction and ischemic driven target vessel revascularization.
Target vessel failure [12 months]
A composite of cardiac death, target vessel myocardial infarction and ischemic driven target vessel revascularization.
Target vessel failure [24 months]
A composite of cardiac death, target vessel myocardial infarction and ischemic driven target vessel revascularization.
All-cause mortality [1 month]
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.
All-cause mortality [12 months]
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.
All-cause mortality [24 months]
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.
Cardiac death [1 month]
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
Cardiac death [12 months]
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
Cardiac death [24 months]
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
Myocardial infarction [1 month]
Procedure and non-procedure related myocardial infarction. Protocol defined.
Myocardial infarction [12 months]
Procedure and non-procedure related myocardial infarction. Protocol defined.
Myocardial infarction [24 months]
Procedure and non-procedure related myocardial infarction. Protocol defined.
Target vessel myocardial infarction [1 month]
As "any myocardial infarction", but with culprit lesion in index vessel.
Target vessel myocardial infarction [12 months]
As "any myocardial infarction", but with culprit lesion in index vessel.
Target vessel myocardial infarction [24 months]
As "any myocardial infarction", but with culprit lesion in index vessel.
Any unplanned revascularization [1 month]
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.
Any unplanned revascularization [12 months]
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.
Any unplanned revascularization [24 months]
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.
Any ischemia driven de novo revascularization [1 month]
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
Any ischemia driven de novo revascularization [12 months]
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
Any ischemia driven de novo revascularization [24 months]
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
Ischemia driven target vessel revascularization [1 month]
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
Ischemia driven target vessel revascularization [12 months]
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
Ischemia driven target vessel revascularization [24 months]
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
Ischemia driven treated target lesion revascularization [1 month]
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
Ischemia driven treated target lesion revascularization [12 months]
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
Ischemia driven treated target lesion revascularization [24 months]
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
Ischemia driven, measured segment revascularization [1 month]
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.
Ischemia driven, measured segment revascularization [12 months]
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.
Ischemia driven, measured segment revascularization [24 months]
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.
Ischemia driven measured segment de novo revascularization [1 month]
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.
Ischemia driven measured segment de novo revascularization [12 months]
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.
Ischemia driven measured segment de novo revascularization [24 months]
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.
Feasibility of QFR [1 hour]
Percentage of successful QFR in patients allocated to a QFR based diagnostic strategy
Feasibility of FFR [1 hour]
Percentage of successfully performed FFR measurements in vessels with attempted FFR (vessel level) Percentages of patients with successful FFR measurements (all attempted)
Number of lesion interrogated [1 hour]
Total number of lesions diagnosed with either QFR or FFR during the procedure
Procedure time [1 hour]
Time from introduction of the sheet until the sheet for coronary access is removed from the patient
Contrast volume [1 hour]
Total volume of contrast used in the procedure
Fluoroscopy time [1 hour]
Total fluoroscopy time for the procedure
Number of stents implanted [1 hour]
Total number of stents implanted during the procedure. Stents implanted in a staged procedure are included

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 72 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aalborg University Hospital	Aalborg		Denmark	9100
2	Aarhus University Hospital	Aarhus N		Denmark	8000
3	Gentofte Hospital	Hellerup		Denmark	2900
4	Odense University Hospital	Odense		Denmark
5	Institut Arnault Tzanck	Saint-Laurent-du-Var	Nice	France	06700
6	GCS ES Axium - Parc Rambot	Aix-en-Provence		France	13097
7	CHU de Lille, Lille University Hospital	Lille		France	59000
8	Institut Cardiovasculaire Paris Sud (ICPS), Hopital Jacques Cartier	Massy		France	91300
9	Hopital Haut-Leveque, Pessac	Pessac		France	33600
10	Hôpital Privé Claude Galien	Quincy		France	91480
11	Clinique Pasteur, Toulouse	Toulouse		France	31076
12	Charite-Universitatsmedizin Berlin	Berlin		Germany	12200
13	Elisabeth Krankenhaus	Essen		Germany	45138
14	Universitätsklinikum Giessen	Giessen		Germany	35392
15	Universitäres Herz- und Gefäßzentrum UKE Hamburg Klinik und Poliklinik für Kardiologie	Hamburg		Germany	20246
16	University Clinic Leipzig	Leipzig		Germany	04103
17	Klinikum Wilhelmshaven GmbH	Wilhelmshaven		Germany	26389
18	Ospedale Maggiore, AUSL Bologna	Bologna		Italy	40133
19	Azienda Ospedaliero-Universitaria di Ferrara, University of Ferrara	Ferrara		Italy	44124
20	Ospedale della Misericordia Grosseto	Grosseto		Italy	58100
21	Azienda Ospedaliero Universitaria Federico II di Napoli	Naples		Italy	80138
22	San Luigi Gonzaga University Hospital, Turin	Orbassano		Italy	10043
23	Arcispedale S. Maria Nuova di Reggio Emilia	Reggio Emilia		Italy	42123
24	Ospedale degli Infermi di Rimini	Rimini		Italy	47923
25	Ospedale di Rivoli, Torino	Torino		Italy	10098
26	Mitsui Memorial Hospital	Tokyo		Japan	101-8643
27	St Luke's International Hospital	Tokyo		Japan	104-8560
28	Riga Stradini University Hospital	Riga		Latvia	1002
29	Hospital of Lithuanian University of Health Sciences Kauno Klinikos	Kaunas		Lithuania	50161
30	VU University Medical Center	Amsterdam		Netherlands	1081
31	Academic Medical Center (AMC)	Amsterdam		Netherlands	1105
32	HagaZiekenhuis	The Hague		Netherlands	2545
33	Medical University of Warsaw	Warsaw		Poland	PL 02-097
34	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar	Murcia	Spain	30120
35	Hospital Clinico de Coruña	Coruña		Spain	15006
36	Hospital Lucus Agusti LUGO	Lugo		Spain	27003
37	Hospital Clinico San Carlos	Madrid		Spain	28040
38	Hospital Clinico de Santiago de Compostela	Santiago De Compostela		Spain	15706
39	Hospital Clinico Universitario de Valladolid	Valladolid		Spain	47003
40	Hospital Álvaro Cunqueiro	Vigo		Spain	36312
41	Sahlgrenska University Hospital	Göteborg		Sweden	413 45
42	Örebro University Hospital	Örebro		Sweden	701 85
43	Barbera Stähli	Zürich	Zûrich	Switzerland	8091