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

Aarhus University Hospital Skejby

Status: Active, not recruiting

Conditions: Coronary Artery Disease

Treatments: Diagnostic Test: FFR-based diagnostic strategy; Diagnostic Test: QFR-based diagnostic strategy

Study type: Interventional

Funder types: Other

Identifiers

NCT03729739

1-10-72-263-18

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,001 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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 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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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2,001 participants in 2 patient groups

QFR-based diagnostic strategy

Experimental group

Description:

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.

Treatment:

Diagnostic Test: QFR-based diagnostic strategy

FFR-based diagnostic strategy

Active Comparator group

Description:

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.

Treatment:

Diagnostic Test: FFR-based diagnostic strategy