FAVORIII: The FAVOR III China Study
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: QFR-guided PCI group If the patient is assigned to QFR-guided PCI, QFR is first measured in all coronary arteries with DS% ≥ 50% and ≤ 90%. Then PCI treatment is performed in lesions with QFR ≤ 0.80, and optimal medicine treatment is prescribed to those with QFR > 0.80. It is strongly recommended to select the device size based on the 3D-QCA measurements in this group. |
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.
Other Names:
Diagnostic Test: Angiography
Coronary angiography is a procedure that uses contrast under x-ray pictures to detect stenosis in the coronary arteries
Other Names:
|
| Active Comparator: Angiography-guided PCI group If the patient is assigned to angiography-guided PCI, then the investigator performs PCI according to the stenosis severity based on visual assessment of the angiogram. No other functional tests such as FFR/iFR can be used for further assessment of the lesion before PCI. |
Diagnostic Test: Angiography
Coronary angiography is a procedure that uses contrast under x-ray pictures to detect stenosis in the coronary arteries
Other Names:
|
Outcome Measures
Primary Outcome Measures
- MACE [1 year]
A composite of all-cause mortality, any myocardial infarction and any ischemia-driven revascularization
Secondary Outcome Measures
- MACE excluding peri-procedural MI (Major secondary endpoint) [1 year]
all-cause mortality, any spontaneous myocardial infarction and any ischemia-driven revascularization
- MACE [1 month, 2 years, 3 years, 4 years and 5 years]
A composite of all-cause mortality, any myocardial infarction and any ischemia-driven
- Death [1 month, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
Cardiovascular, non-cardiovascular and undetermined death
- MI [1 month, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
Target vessel related and non-target vessel related MI
- Target vessel revascularization (TVR) [1 month, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
The ischemia driven and non-ischemia driven TVR
- Any coronary artery revascularization [1 month, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
The The ischemia driven and non-ischemia driven Revascularization
- Definite or probable stent thrombosis [1 month, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
Definite and probable stent thrombosis during acute, sub-acute, late, and very late phase according to the Academic Research Consortium (ARC)-2
- The PCI strategy changes based on the QFR and 3D-QCA [During the procedure]
PCI strategy changes following QFR and three-dimension quantitative coronary angiography (3D-QCA)
- Cost during 1-year follow-up [1 month, 6 months, 1 year]
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.
- Quality-adjusted-life-years (QALYs) index [1 month, 6 months, 1 year]
QALYs determined using EuroQol five dimensions questionnaire (EQ-5D) in official Chinese version, to assess the quality of life.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences | Beijing | Beijing | China | 100037 |
Sponsors and Collaborators
- China National Center for Cardiovascular Diseases
Investigators
- Principal Investigator: Bo Xu, MBBS, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences
- Principal Investigator: Shubin Qiao, MD, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
- De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, Jagic N, Möbius-Winkler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engström T, Oldroyd KG, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Jüni 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 Möbius-Winkler, Sven].
- 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.
- Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrøm 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.
- 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.
- 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, Bøtker 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). pii: e009603. doi: 10.1161/JAHA.118.009603.
- 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.
- FAVOR III China - 2508