The FAVOR III China Study

Coronary Artery Disease Clinical Trial

— FAVORIII  

Official title:

Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous InterVention in Patients With cORonary Artery Disease (The FAVOR III China Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03656848
• Other study ID #: FAVOR III China - 2508
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 25, 2018
• Est. completion date: February 19, 2025

Study information

• Verified date: December 2022
• Source: China National Center for Cardiovascular Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall purpose of the FAVOR III China trial is to investigate if a strategy of quantitative flow ratio (QFR)-guided percutaneous coronary intervention (PCI) yields superior clinical outcome and cost-effectiveness compared to a strategy of standard coronary angiography-guided PCI in evaluation of patients with coronary artery disease.

Description:

The FAVOR III China is a prospective, multicenter, blinded, randomized, superiority clinical trial comparing the clinical outcome and cost-effectiveness of the two PCI strategies, QFR-augmented angiography-guided (QFR-guided) strategy versus an angiography-only-guided (angiography-guided) strategy , in evaluation of patients with coronary artery disease (CAD). The study is adequately powered to detect if the primary outcome by the QFR-guided PCI strategy is superior to the standard angiography-guided PCI strategy. The hypothesis is that a QFR-guided PCI strategy results in superior clinical outcome, assessed by rate of Major Adverse Cardiac Events (MACE) defined as a composite of all-cause mortality, any myocardial infarction (MI) and any ischemia-driven revascularization at 1 year, compared to a standard angiography-guided PCI strategy. If QFR-guided strategy is shown to be superior to the angiography-guided strategy, the lower clinical costs and better clinical outcome by QFR may suggest it to be the preferred strategy for invasive functional evaluation of coronary artery stenosis.

The primary and major secondary endpoints will be analyzed in prespecified subgroups, including age, sex, diabetes, smoking status, acute coronary syndrome, body mass index, left ventricular ejection fraction, lesion location, length and reference vessel diameter, stenosis severity, multivessel disease, calcified lesion, bifurcation, tandem and bending/tortuous lesion, QFR gray zone (0.75-0.85), QFR based functional and residual functional SYNTAX score, residual QFR, center experience for invasive physiology, and learning experience with QFR.

For the purpose of protecting trial subjects and study personnel while maintaining trial data integrity during the coronavirus disease 2019 (COVID-19) pandemic, we particularly arranged an unscheduled telephone follow-up for all the participants, to evaluate the potential impact of the pandemic. Using a special designed follow-up questionnaire, all subjects were required to report the presence of COVID-19 infection and its related complications, any possible ischemia symptom, any hospitalization or outpatient visit, and interruption of cardiovascular medicine during this time (from Jan 20, 2019 to May 1, 2020). Clinical event committees (CEC) will update the working protocol to enable the re-adjudication of events from the onset of the pandemic to the end of the trial. All the events will be classified as related, possibly related, or not related to COVID-19 infection. To identify the interaction between COVID-19 pandemic and randomized revascularization strategy in the current study, several prespecified subsets will be added to the subgroups analysis, including COVID-19 positive vs. negative subjects, pre-pandemic vs. during pandemic vs. post-pandemic subjects, and the sites located at the high-risk region vs. low- to mediate-risk region.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 3847
• Est. completion date: February 19, 2025
• Est. primary completion date: February 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

General inclusion criteria:

• Age = 18 years

• Stable or unstable angina pectoris, or post-acute myocardial infarction (= 72 hrs)

• Signed written informed consent

• Eligible for PCI by the operators

Angiographic inclusion criteria:

• At least one lesion is present of DS% =50% and =90% in one major native epicardial coronary artery and supplying viable myocardium

• Reference lumen diameter = 2.5mm by visual assessment

Exclusion Criteria:

General exclusion criteria:

• Cardiogenic shock or severe heart failure (NYHA =III)

• Severely impaired renal function: creatinine > 150µmol/L or Cockcroft-Gault calculated GFR < 45 ml/kg/1.73 m2

• Allergy to iodine-containing contrast agents

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

• Life expectancy less than one year

Angiographic exclusion criteria:

• With only one coronary artery lesion(DS%>90%)with TIMI flow < 3

• Target stenoses are culprit lesions related with acute myocardial infarction

• Target stenoses in the vessel involving myocardial bridge

• Poor angiographic image quality precluding vessel contour detection or with suboptimal contrast filling

• Severe overlap in the stenosed segment or severe tortuosity of any target vessel deemed unable for QFR measurement

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Circulation
• Coronary Disease
• Coronary Stenosis
• Ischemia
• Myocardial Ischaemia
• Myocardial Ischemia
• Percutaneous Coronary Intervention

Intervention

Diagnostic Test:
• QFR
QFR is a novel method for evaluating the functional significance of coronary stenosis by calculation of the pressure drop in the vessel based on two angiographic projections.
• Angiography
Coronary angiography is a procedure that uses contrast under x-ray pictures to detect stenosis in the coronary arteries

Locations

Country	Name	City	State
China	Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
China National Center for Cardiovascular Diseases

Country where clinical trial is conducted

China, 

References & Publications (9)

De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, Jagic N, Mobius-Winkler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engstrom T, Oldroyd KG, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Juni P, Fearon WF; FAME 2 Trial Investigators. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012 Sep 13;367(11):991-1001. doi: 10.1056/NEJMoa1205361. Epub 2012 Aug 27. Erratum In: N Engl J Med. 2012 Nov;367(18):1768. Mobius-Winckler, Sven [corrected to Mobius-Winkler, Sven]. — View Citation

Jin Z, Xu B, Yang X, Jia R, Meng S, Hu H, Deng Y, Cao X, Ruan Y, Han J, Liu J, Qu X, Zhou Y, Wang J, Fu G, Yu B, Wang Y, Guan C, Song L, Tu S, Qiao S, Stone GW; FAVOR III China Study Group. Coronary Intervention Guided by Quantitative Flow Ratio vs Angiog — View Citation

Song L, Tu S, Sun Z, Wang Y, Ding D, Guan C, Xie L, Escaned J, Fearon WF, Kirtane AJ, Serruys PW, Wijns W, Windecker S, Leon MB, Stone GW, Qiao S, Xu B; FAVOR III China Investigators. Quantitative flow ratio-guided strategy versus angiography-guided strategy for percutaneous coronary intervention: Rationale and design of the FAVOR III China trial. Am Heart J. 2020 May;223:72-80. doi: 10.1016/j.ahj.2020.02.015. Epub 2020 Feb 24. — View Citation

Song L, Xu B, Tu S, Guan C, Jin Z, Yu B, Fu G, Zhou Y, Wang J, Chen Y, Pu J, Chen L, Qu X, Yang J, Liu X, Guo L, Shen C, Zhang Y, Zhang Q, Pan H, Zhang R, Liu J, Zhao Y, Wang Y, Dou K, Kirtane AJ, Wu Y, Wijns W, Yang W, Leon MB, Qiao S, Stone GW; FAVOR II — View Citation

Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009 Jan 15;360(3):213-24. doi: 10.1056/NEJMoa0807611. — View Citation

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

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

Xu B, Tu S, Song L, Jin Z, Yu B, Fu G, Zhou Y, Wang J, Chen Y, Pu J, Chen L, Qu X, Yang J, Liu X, Guo L, Shen C, Zhang Y, Zhang Q, Pan H, Fu X, Liu J, Zhao Y, Escaned J, Wang Y, Fearon WF, Dou K, Kirtane AJ, Wu Y, Serruys PW, Yang W, Wijns W, Guan C, Leon — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MACE	A composite of all-cause mortality, any myocardial infarction and any ischemia-driven revascularization	1 year
Secondary	MACE excluding peri-procedural MI (Major secondary endpoint)	all-cause mortality, any spontaneous myocardial infarction and any ischemia-driven revascularization	1 year
Secondary	MACE	A composite of all-cause mortality, any myocardial infarction and any ischemia-driven	1 month, 2 years, 3 years, 4 years and 5 years
Secondary	Death	Cardiovascular, non-cardiovascular and undetermined death	1 month, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years
Secondary	MI	Target vessel related and non-target vessel related MI	1 month, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years
Secondary	Target vessel revascularization (TVR)	The ischemia driven and non-ischemia driven TVR	1 month, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years
Secondary	Any coronary artery revascularization	The The ischemia driven and non-ischemia driven Revascularization	1 month, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years
Secondary	Definite or probable stent thrombosis	Definite and probable stent thrombosis during acute, sub-acute, late, and very late phase according to the Academic Research Consortium (ARC)-2	1 month, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years
Secondary	The PCI strategy changes based on the QFR and 3D-QCA	PCI strategy changes following QFR and three-dimension quantitative coronary angiography (3D-QCA)	During the procedure
Secondary	Cost during 1-year follow-up	Costs include direct clinical costs during the initial hospitalization and other resources used, main cardiovascular medication expenses, and outpatient and/or hospitalization expenses associated with MACE.	1 month, 6 months, 1 year
Secondary	Quality-adjusted-life-years (QALYs) index	QALYs determined using EuroQol five dimensions questionnaire (EQ-5D) in official Chinese version, to assess the quality of life.	1 month, 6 months, 1 year