A Comparison of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Patients With Multivessel Coronary Artery Disease

Coronary Disease Clinical Trial

— FAME 3  

Official title:

Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 3 Trial A Comparison of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Patients With Multivessel Coronary Artery Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02100722
• Other study ID #: FAME 3
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 25, 2014
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether Fractional flow reserve (FFR, (coronary pressure wire-based index for assessing the ischemic potential of a coronary lesion)-guided percutaneous coronary intervention (PCI) in patients with multivessel coronary artery disease (CAD) will result in similar outcomes to coronary artery bypass graft surgery (CABG).

Description:

The FAME 3 trial is a multicenter, international, randomized, controlled noninferiority trial. All patients with multivessel CAD (not involving the left main) will be screened by the site's Heart Team (including but not limited to an interventional cardiologist, cardiac surgeon and research coordinator). If all agree that the patient can be treated either with FFR-guided PCI or CABG, and all inclusion criteria are met and no exclusion criteria are met, then the patient will be randomized. Baseline clinical, functional, laboratory and electrocardiographic data will be obtained. Patients will receive treatment within 4 weeks of randomization. Patients randomized to CABG will receive state of the art therapy at the discretion of the local surgeon with a strong emphasis on arterial revascularization. Patients undergoing PCI will have FFR measured with a St. Jude Medical coronary pressure wire across all lesions. If the FFR is ≤0.80, then PCI will be performed with the Medtronic Resolute Integrity drug-eluting stent (DES) as per usual routine. If the FFR is >0.80 then PCI will be deferred. All patients will receive medical therapy as per published guidelines. Patients will follow-up at 1 and 6 months, and 1 and 3 years with an evaluation of clinical status, functional status, medications and events. Follow-up may be extended to 5 years, if funding allows. Core lab analyses will include formal quantitative coronary angiography (QCA) of the baseline angiograms with calculation of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score and Functional SYNTAX Score.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1500
• Est. completion date: December 2024
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• 1. Age = 21 years with angina and/or evidence of myocardial ischemia
• 2. Three vessel CAD, defined as = 50% diameter stenosis by visual estimation in each of the three major epicardial vessels or major side branches, but not involving left main coronary artery, and amenable to revascularization by both PCI and CABG as determined by the Heart Team. Patients with a non-dominant right coronary artery may be included if only the left anterior descending artery (LAD) and left circumflex have =50% stenosis
• 3. Willing and able to provide informed, written consent

Exclusion Criteria:

• 1. Requirement for other cardiac or non-cardiac surgical procedure (e.g., valve replacement, carotid revascularization)
• 2. Cardiogenic shock and/or need for mechanical/pharmacologic hemodynamic support
• 3. Recent STEMI (<5 days prior to randomization)
• 4. Ongoing Non STEMI with biomarkers (cardiac troponin) still rising
• 5. Known left ventricular ejection fraction <30%
• 6. Life expectancy < 2 years
• 7. Requiring renal replacement therapy
• 8. Undergoing evaluation for organ transplantation
• 9. Participation or planned participation in another clinical trial, except for observational registries
• 10. Pregnancy
• 11. Inability to take dual antiplatelet therapy for six months
• 12. Previous CABG
• 13. Left main disease requiring revascularization
• 14. Extremely calcified or tortuous vessels precluding FFR measurement
• 15. Any target lesion with in-stent drug-eluting stent restenosis

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Stenosis
• Myocardial Ischemia

Intervention

Procedure:
• FFR guided PCI

• CABG
Coronary Artery Bypass Graft Surgery (CABG)

Device:
• Resolute Integrity Stent
Durable polymer zotarolimus-eluting stent
• Resolute Onyx Stent
Durable polymer zotarolimus-eluting stent

Locations

Country	Name	City	State
Australia	Peninsula Health	Frankston
Australia	St. Vincent's Hospital Melbourne	Melbourne
Australia	Concord Hospital	Sydney
Australia	Royal North Shore	Sydney
Australia	University of Sydney	Sydney
Belgium	Cardiovascular Center Aalst	Aalst
Canada	Le'Centre Hospitalier de l'Universite de Montreal	Montreal
Canada	York PCI Group INC	Ontario
Canada	University of Ottawa Heart Institute	Ottawa
Czechia	Masaryk University and University Hospital Brno	Brno
Denmark	Rigshospitalet University Hospital	Copenhagen
France	Cardiovascular Hospital	Lyon
Hungary	Hungarian Institute of Cardiology	Budapest
Korea, Republic of	Asan Medical Center	Seoul
Lithuania	Vilnius University Hospital Santariskiu Klinikos	Vilnius
Netherlands	Catharina Hospital Eindhoven	Eindhoven
Netherlands	HagaZiekenhuis	The Hague
Netherlands	Isala Klinieken	Zwolle
New Zealand	Waikato Hospital	Hamilton
Norway	Stavanger University Hospital	Stavanger
Serbia	University Clinical Center of Serbia	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Sweden	Sahlgrenska University Hospital	Goteborg
Sweden	Danderyds Sjukhus	Stockholm
Sweden	Karolinska Institutet, Dep of clinical science and education, Södersjukhuset	Stockholm
United Kingdom	Wales Heart Research Institute	Cardiff
United Kingdom	University Hospitals Coventry and Warwickshire	Coventry And Warwickshire
United Kingdom	Golden Jubilee National Hospital	Glasgow
United Kingdom	Kings College Hospital	London
United Kingdom	St. Thomas' Hospital	London
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	Oxford University Hospital NHS Trust	Oxford
United Kingdom	Southampton University Hospitals NHS Trust	Southhampton
United States	University of Virginia	Charlottesville	Virginia
United States	Jesse Brown VA Medical Center	Chicago	Illinois
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Houston Methodist Hospital	Houston	Texas
United States	University of Kansas Medical Center	Lawrence	Kansas
United States	Lexinton VA	Lexington	Kentucky
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Centennial Heart	Nashville	Tennessee
United States	Palo Alto VA	Palo Alto	California
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	HealthEast St. Joseph's Hospital	Saint Paul	Minnesota
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Stanford University	Stanford	California

Sponsors (10)

Lead Sponsor	Collaborator
Stanford University	Abbott Medical Devices, Catharina Ziekenhuis Eindhoven, Genae, Golden Jubilee National Hospital, Houston Methodist DeBakey Heart and Vascular Center, Houston, King's College Hospital, London, Medtronic, University of California, Irvine, VZW Cardiovascular Research Center Aalst

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Denmark,  France,  Hungary,  Korea, Republic of,  Lithuania,  Netherlands,  New Zealand,  Norway,  Serbia,  Sweden,  United Kingdom, 

References & Publications (3)

Fearon WF, Zimmermann FM, De Bruyne B, Piroth Z, van Straten AHM, Szekely L, Davidavicius G, Kalinauskas G, Mansour S, Kharbanda R, Ostlund-Papadogeorgos N, Aminian A, Oldroyd KG, Al-Attar N, Jagic N, Dambrink JE, Kala P, Angeras O, MacCarthy P, Wendler O — View Citation

Zimmermann FM, De Bruyne B, Pijls NH, Desai M, Oldroyd KG, Park SJ, Reardon MJ, Wendler O, Woo J, Yeung AC, Fearon WF. Rationale and design of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 Trial: a comparison of fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. Am Heart J. 2015 Oct;170(4):619-626.e2. doi: 10.1016/j.ahj.2015.06.024. Epub 2015 Jul 9. — View Citation

Zimmermann FM, De Bruyne B, Pijls NHJ, Desai M, Oldroyd KG, Reardon MJ, Wendler O, Woo J, Yeung AC, Fearon WF. A protocol update of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 trial: A comparison of fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. Am Heart J. 2019 Aug;214:156-157. doi: 10.1016/j.ahj.2019.04.012. Epub 2019 Apr 29. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MACCE	Death, MI, stroke and any repeat revascularization (MACCE) will be evaluated at 1 year, where subjects contribute data from time of randomization until the occurrence of MACCE or one year follow-up, whichever occurs first. Subjects who die or are lost to follow up before 1 year will be censored at their last recorded activity.	1 year
Secondary	Key Secondary Outcome: Composite of Death From Any Cause, Myocardial Infarction, or Stroke	Death, MI, or stroke at 3-year follow-up	3 years
Secondary	Number of Participants Experiencing Death, MI, or Stroke	Subjects who died or are lost to follow up before this time were censored at their last recorded activity.	1 year
Secondary	Death	Death evaluated excluding patients lost to follow-up from each arm	1 year
Secondary	Number of Participants Experiencing Myocardial Infarction	MI evaluated excluding patients lost to follow-up from each arm	1 year
Secondary	Number of Participants Experiencing Stroke	Stroke evaluated excluding patients lost to follow-up from each arm.	1 year
Secondary	Number of Participants Requiring Repeat Revascularization	Any repeat revascularization evaluated excluding patients lost to follow-up from each arm	1 year
Secondary	Number of Participants Experiencing BARC Type 3-5 Bleeding	Bleeding Academic Research Consortium (BARC) type 3-5 indicates severe bleeding.	1 year
Secondary	Number of Participants Experiencing Acute Kidney Injury		1 year
Secondary	Number of Participants Experiencing Atrial Fibrillation or Clinically Significant Arrhythmia		1 year
Secondary	Number of Participants Experiencing Definite Stent Thrombosis		1 year
Secondary	Number of Participants Experiencing Definite Symptomatic Graft Occlusion		1 year
Secondary	Number of Participants Requiring Rehospitalization Within 30 Days		30 days
Secondary	MACCE	Death, MI, stroke and any repeat revascularization (MACCE) rate at 2 years, 3 years and 5 years	2 years, 3 years, 5 years
Secondary	Death, MI, or Stroke at 5 Years	Death, MI, or stroke at 5 years	5 years
Secondary	Individual Components of Primary Outcome	Individual components of primary outcome: number of participants experiencing death, myocardial infarction, and stroke	At year 3

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