Functional Assessment by Virtual Online Reconstruction. The FAVOR III Europe Trial

NCT ID: NCT03729739

Last Updated: 2024-07-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 2001 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-06
• Study Completion Date: 2025-12-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

QFR-based diagnostic strategy

Intervention Type: DIAGNOSTIC_TEST

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

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.

Group Type: ACTIVE_COMPARATOR

FFR-based diagnostic strategy

Intervention Type: DIAGNOSTIC_TEST

Standard FFR based diagnostic method. Pressure drop across the stenosis is measured with a pressure wire during medical induced hyperaemic conditions

Interventions

QFR-based diagnostic strategy

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

Intervention Type: 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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medis Medical Imaging Systems

UNKNOWN

Sponsor Role: collaborator

Aarhus University Hospital Skejby

OTHER

Sponsor Role: lead

Responsible Party

Evald Hoej Christiansen

Consultant cardiologist, Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Evald H. Christiansen, Prof.

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital, Denmark

Locations

Aalborg University Hospital

Aalborg, , Denmark

Aarhus University Hospital

Aarhus N, , Denmark

Gentofte Hospital

Hellerup, , Denmark

Institut Arnault Tzanck

Saint-Laurent-du-Var, Nice, 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

Clinique Pasteur, Toulouse

Toulouse, , France

Charite-Universitatsmedizin Berlin

Berlin, , Germany

Elisabeth Krankenhaus

Essen, , Germany

University Clinic Leipzig

Leipzig, , Germany

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, , Italy

Riga Stradini University Hospital

Riga, , Latvia

Hospital of Lithuanian University of Health Sciences Kauno Klinikos

Kaunas, , Lithuania

VU University Medical Center

Amsterdam, , Netherlands

Academic Medical Center (AMC)

Amsterdam, , Netherlands

HagaZiekenhuis

The Hague, , Netherlands

Medical University of Warsaw

Warsaw, , Poland

Hospital Clinico Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

Hospital Clinico de Coruña

A Coruña, , Spain

Hospital Lucus Agusti LUGO

Lugo, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Clinico Universitario de Valladolid

Valladolid, , Spain

Hospital Álvaro Cunqueiro

Vigo, , Spain

Sahlgrenska University Hospital

Gothenburg, , Sweden

Barbera Stähli

Zurich, Zûrich, Switzerland

Countries

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

References

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.

Reference Type: BACKGROUND

PMID: 27712739 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 29101020 (View on PubMed)

Andersen 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.

Reference Type: DERIVED

PMID: 39488224 (View on PubMed)

Other Identifiers

1-10-72-263-18

Identifier Type: -

Identifier Source: org_study_id