Coronary Artery DiseaseNCT03729739
Functional Assessment by Virtual Online Reconstruction. The FAVOR III Europe Trial
A study testing QFR-based diagnostic strategy and FFR-based diagnostic strategy in people with Coronary Artery Disease, run by Aarhus University Hospital Skejby at 35 sites in 11 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- QFR-based diagnostic strategy and FFR-based diagnostic strategy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,001 participants
- Where
- 35 sitesin 11 countries
- Study dates
- 6 Nov 2018to 31 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
35 sites in 11 countries.
35 sites in 11 countries
Italy8 sites
Ospedale Maggiore, AUSL Bologna
Bologna, 40133
Azienda Ospedaliero-Universitaria di Ferrara, University of Ferrara
Ferrara, 44124
Azienda Ospedaliero Universitaria Federico II di Napoli
Naples, 80138
San Luigi Gonzaga University Hospital, Turin
Orbassano, 10043
Arcispedale S. Maria Nuova di Reggio Emilia
Reggio Emilia, 42123
Ospedale degli Infermi di Rimini
Rimini, 47923
Ospedale di Rivoli, Torino
Torino, 10098
Azienda Ospedaliera Universitaria integrata Verona
Verona, 37126
France7 sites
GCS ES Axium - Parc Rambot
Aix-en-Provence, 13097
CHU de Lille, Lille University Hospital
Lille, 59000
Institut Cardiovasculaire Paris Sud (ICPS), Hopital Jacques Cartier
Massy, 91300
Hopital Haut-Leveque, Pessac
Pessac, 33600
Hôpital Privé Claude Galien
Quincy, 91480
Institut Arnault Tzanck
Saint-Laurent-du-Var, Nice, 06700
Clinique Pasteur, Toulouse
Toulouse, 31076
Spain6 sites
Hospital Clinico de Coruña
A Coruña, 15006
Hospital Clinico Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120
Hospital Lucus Agusti LUGO
Lugo, 27003
Hospital Clinico San Carlos
Madrid, 28040
Hospital Clinico Universitario de Valladolid
Valladolid, 47003
Hospital Álvaro Cunqueiro
Vigo, 36312
Denmark3 sites
Aalborg University Hospital
Aalborg, 9100
Aarhus University Hospital
Aarhus N, 8000
Gentofte Hospital
Hellerup, 2900
Germany3 sites
Charite-Universitatsmedizin Berlin
Berlin, 12200
Elisabeth Krankenhaus
Essen, 45138
University Clinic Leipzig
Leipzig, 04103
Netherlands3 sites
VU University Medical Center
Amsterdam, 1081
Academic Medical Center (AMC)
Amsterdam, 1105
HagaZiekenhuis
The Hague, 2545
Lithuania1 site
Hospital of Lithuanian University of Health Sciences Kauno Klinikos
Kaunas, 50161
About this study
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
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.
Read the 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.
- Conditions
- Coronary Artery Disease
- Being tested
- QFR-based diagnostic strategy, FFR-based diagnostic strategy
- Keywords
- Fractional Flow Reserve (FFR), Quantitative Flow Ratio (QFR), Stable coronary artery disease, Angina pectoris, Angiography derived fractional flow reserve
- Medical subject headings
- Coronary Artery Disease, Angina Pectoris
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QFR-based diagnostic strategyDiagnostic test
Novel computer based calculation of lesion severity. Pressure wire-free and adenosine-free
FFR-based diagnostic strategyDiagnostic test
Standard FFR based diagnostic method. Pressure drop across the stenosis is measured with a pressure wire during medical induced hyperaemic conditions
| Study group | Role | What they receive |
|---|---|---|
| QFR-based diagnostic strategy | Experimental | 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. Receives: Diagnostic Test: QFR-based diagnostic strategy |
| FFR-based diagnostic strategy | Active comparator | 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. Receives: Diagnostic Test: FFR-based diagnostic strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient oriented composite endpoint (PoCE)
A composite endpoint of 1) all-cause mortality, 2) any myocardial infarction, and 3) any unplanned revascularization
Measured: 12 months
Secondary outcomes (40)
Target vessel failure
A composite of cardiac death, target vessel myocardial infarction and ischemic driven target vessel revascularization.
Measured: 1 month
Target vessel failure
A composite of cardiac death, target vessel myocardial infarction and ischemic driven target vessel revascularization.
Measured: 12 months
Target vessel failure
A composite of cardiac death, target vessel myocardial infarction and ischemic driven target vessel revascularization.
Measured: 24 months
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.
Measured: 1 month
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.
Measured: 12 months
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.
Measured: 24 months
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
Measured: 1 month
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
Measured: 12 months
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
Measured: 24 months
Myocardial infarction
Procedure and non-procedure related myocardial infarction. Protocol defined.
Measured: 1 month
Myocardial infarction
Procedure and non-procedure related myocardial infarction. Protocol defined.
Measured: 12 months
Myocardial infarction
Procedure and non-procedure related myocardial infarction. Protocol defined.
Measured: 24 months
Target vessel myocardial infarction
As "any myocardial infarction", but with culprit lesion in index vessel.
Measured: 1 month
Target vessel myocardial infarction
As "any myocardial infarction", but with culprit lesion in index vessel.
Measured: 12 months
Target vessel myocardial infarction
As "any myocardial infarction", but with culprit lesion in index vessel.
Measured: 24 months
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.
Measured: 1 month
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.
Measured: 12 months
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.
Measured: 24 months
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
Measured: 1 month
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
Measured: 12 months
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
Measured: 24 months
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
Measured: 1 month
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
Measured: 12 months
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
Measured: 24 months
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
Measured: 1 month
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
Measured: 12 months
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
Measured: 24 months
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.
Measured: 1 month
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.
Measured: 12 months
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.
Measured: 24 months
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.
Measured: 1 month
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.
Measured: 12 months
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.
Measured: 24 months
Feasibility of QFR
Percentage of successful QFR in patients allocated to a QFR based diagnostic strategy
Measured: 1 hour
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)
Measured: 1 hour
Number of lesion interrogated
Total number of lesions diagnosed with either QFR or FFR during the procedure
Measured: 1 hour
Procedure time
Time from introduction of the sheet until the sheet for coronary access is removed from the patient
Measured: 1 hour
Contrast volume
Total volume of contrast used in the procedure
Measured: 1 hour
Fluoroscopy time
Total fluoroscopy time for the procedure
Measured: 1 hour
Number of stents implanted
Total number of stents implanted during the procedure. Stents implanted in a staged procedure are included
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2018
- Study start6 Nov 2018
- Primary completion21 Jul 2023
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized clinical non-inferiority trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2,001 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital Skejby
- Sponsor type
- University, hospital or other
- Collaborators
- Medis Medical Imaging Systems
- Responsible party
- Principal investigator, Evald Hoej Christiansen, Aarhus University Hospital Skejby
- Investigators
- Evald H. Christiansen, Prof., Principal investigator, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03729739
- Sponsor's protocol ID
- 1-10-72-263-18
- Status last verified
- Jul 2024
- First submitted
- 1 Nov 2018
- Last updated
- 24 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 27712739Westra 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.
PubMed 29980523Westra 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.
PubMed 29555835Xu 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.
PubMed 29101020Andersen BK, Sejr-Hansen M, Maillard L, Campo G, Ramunddal T, Stahli BE, Guiducci V, Serafino LD, Escaned J, Santos IA, Lopez-Palop R, Landmesser U, Dieu RS, Mejia-Renteria H, Koltowski L, Ziubryte G, Cetran L, Adjedj J, Abdelwahed YS, Liu T, Mogensen LJH, Eftekhari A, Westra J, Lenk K, Casella G, Van Belle E, Biscaglia S, Olsen NT, Knaapen P, Kochman J, Santos RC, Scarsini R, Christiansen EH, Holm NR. Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial. Lancet. 2024 Nov 9;404(10465):1835-1846. doi: 10.1016/S0140-6736(24)02175-5. Epub 2024 Oct 30.
PubMed 39488224
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03729739
- Acronym / sponsor ID
- 1-10-72-263-18
- Conditions
- Coronary Artery Disease
- Keywords
- Fractional Flow Reserve (FFR), Quantitative Flow Ratio (QFR), Stable coronary artery disease, Angina pectoris, Angiography derived fractional flow reserve
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,001 participants (actual)
- Lead sponsor
- Aarhus University Hospital SkejbyUniversity, hospital or other
- Collaborators
- Medis Medical Imaging Systems
- Study start
- 6 Nov 2018 (actual)
- Primary completion
- 21 Jul 2023 (actual)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 5 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized clinical non-inferiority trial
| Arm | Type | Receives |
|---|---|---|
| QFR-based diagnostic strategy | Experimental | Diagnostic Test: QFR-based diagnostic strategyIntermediate 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. |
| FFR-based diagnostic strategy | Active comparator | Diagnostic Test: FFR-based diagnostic strategyIntermediate 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QFR-based diagnostic strategyNovel computer based calculation of lesion severity. Pressure wire-free and adenosine-free | Diagnostic test | QFR-based diagnostic strategy |
| FFR-based diagnostic strategyStandard FFR based diagnostic method. Pressure drop across the stenosis is measured with a pressure wire during medical induced hyperaemic conditions | Diagnostic test | FFR-based diagnostic strategy |
Primary outcome
Patient oriented composite endpoint (PoCE)
Time frame: 12 months
A composite endpoint of 1) all-cause mortality, 2) any myocardial infarction, and 3) any unplanned revascularization
40 secondary outcomes
Target vessel failure
Time frame: 1 month
Target vessel failure
Time frame: 12 months
Target vessel failure
Time frame: 24 months
All-cause mortality
Time frame: 1 month
All-cause mortality
Time frame: 12 months
All-cause mortality
Time frame: 24 months
Cardiac death
Time frame: 1 month
Cardiac death
Time frame: 12 months
Cardiac death
Time frame: 24 months
Myocardial infarction
Time frame: 1 month
Myocardial infarction
Time frame: 12 months
Myocardial infarction
Time frame: 24 months
Target vessel myocardial infarction
Time frame: 1 month
Target vessel myocardial infarction
Time frame: 12 months
Target vessel myocardial infarction
Time frame: 24 months
Any unplanned revascularization
Time frame: 1 month
Any unplanned revascularization
Time frame: 12 months
Any unplanned revascularization
Time frame: 24 months
Any ischemia driven de novo revascularization
Time frame: 1 month
Any ischemia driven de novo revascularization
Time frame: 12 months
Any ischemia driven de novo revascularization
Time frame: 24 months
Ischemia driven target vessel revascularization
Time frame: 1 month
Ischemia driven target vessel revascularization
Time frame: 12 months
Ischemia driven target vessel revascularization
Time frame: 24 months
Ischemia driven treated target lesion revascularization
Time frame: 1 month
Ischemia driven treated target lesion revascularization
Time frame: 12 months
Ischemia driven treated target lesion revascularization
Time frame: 24 months
Ischemia driven, measured segment revascularization
Time frame: 1 month
Ischemia driven, measured segment revascularization
Time frame: 12 months
Ischemia driven, measured segment revascularization
Time frame: 24 months
Ischemia driven measured segment de novo revascularization
Time frame: 1 month
Ischemia driven measured segment de novo revascularization
Time frame: 12 months
Ischemia driven measured segment de novo revascularization
Time frame: 24 months
Feasibility of QFR
Time frame: 1 hour
Feasibility of FFR
Time frame: 1 hour
Number of lesion interrogated
Time frame: 1 hour
Procedure time
Time frame: 1 hour
Contrast volume
Time frame: 1 hour
Fluoroscopy time
Time frame: 1 hour
Number of stents implanted
Time frame: 1 hour
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2024.
- Background: PubMed 27712739Tu 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.
- Background: PubMed 29980523Westra 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.
- Background: PubMed 29555835Westra 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.
- Background: PubMed 29101020Xu 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.
- Derived from this study: PubMed 39488224Andersen BK, Sejr-Hansen M, Maillard L, Campo G, Ramunddal T, Stahli BE, Guiducci V, Serafino LD, Escaned J, Santos IA, Lopez-Palop R, Landmesser U, Dieu RS, Mejia-Renteria H, Koltowski L, Ziubryte G, Cetran L, Adjedj J, Abdelwahed YS, Liu T, Mogensen LJH, Eftekhari A, Westra J, Lenk K, Casella G, Van Belle E, Biscaglia S, Olsen NT, Knaapen P, Kochman J, Santos RC, Scarsini R, Christiansen EH, Holm NR. Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial. Lancet. 2024 Nov 9;404(10465):1835-1846. doi: 10.1016/S0140-6736(24)02175-5. Epub 2024 Oct 30.
- Individual participant dataSharing planned: Undecided
Related trials for Coronary Artery Disease
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Active, not recruiting
Shockwave™ vs Surgical Endarterectomy for Calcified Severe Common Femoral Artery Stenosis: Comparison of Efficacy, Safety and Long-Term Outcomes
Common Femoral Artery Stenosis, Calcification; Heart
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
Active, not recruiting
The OCTOBER Trial - European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction (OCTOBER)
Ischaemic Heart Disease, Ischemic Heart Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Evald H. Christiansen, Prof. principal investigator
Aarhus University Hospital
35 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing QFR-based diagnostic strategy and FFR-based diagnostic strategy in people with Coronary Artery Disease, run by Aarhus University Hospital Skejby at 35 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in Italy, France, Spain, Denmark, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient oriented composite endpoint (PoCE) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03729739, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2024.