Clinical trial NCT02100722: A Comparison of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Patients With Multivessel Coronary Artery Disease
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Coronary Disease
Coronary Stenosis
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: VZW Cardiovascular Research Center Aalst
name: Catharina Ziekenhuis Eindhoven
name: Golden Jubilee National Hospital
name: University of California, Irvine
name: Medtronic
name: Abbott Medical Devices
name: Genae
name: King's College Hospital NHS Trust
name: Houston Methodist DeBakey Heart & Vascular Center
First posted: 2014-04-01
Enrollment: 1500
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: MACCE
timeFrame: 1 year
Secondary outcomes:
measure: Key Secondary Outcome: Composite of Death From Any Cause, Myocardial Infarction, or Stroke
timeFrame: 3 years
measure: Number of Participants Experiencing Death, MI, or Stroke
timeFrame: 1 year
measure: Death
timeFrame: 1 year
measure: Number of Participants Experiencing Myocardial Infarction
timeFrame: 1 year
measure: Number of Participants Experiencing Stroke
timeFrame: 1 year
measure: Number of Participants Requiring Repeat Revascularization
timeFrame: 1 year
measure: Number of Participants Experiencing BARC Type 3-5 Bleeding
timeFrame: 1 year
measure: Number of Participants Experiencing Acute Kidney Injury
timeFrame: 1 year
measure: Number of Participants Experiencing Atrial Fibrillation or Clinically Significant Arrhythmia
timeFrame: 1 year
measure: Number of Participants Experiencing Definite Stent Thrombosis
timeFrame: 1 year
measure: Number of Participants Experiencing Definite Symptomatic Graft Occlusion
timeFrame: 1 year
measure: Number of Participants Requiring Rehospitalization Within 30 Days
timeFrame: 30 days
measure: MACCE
timeFrame: 2 years, 3 years, 5 years
measure: Death, MI, or Stroke at 5 Years
timeFrame: 5 years
measure: Individual Components of Primary Outcome
timeFrame: At year 3
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Palo Alto VA
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Chicago
country: United States
facility: Jesse Brown VA Medical Center
state: Illinois
city: Lawrence
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Lexinton VA
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Saint Paul
country: United States
facility: HealthEast St. Joseph's Hospital
state: Minnesota
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Centennial Heart
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Frankston
country: Australia
facility: Peninsula Health
city: Melbourne
country: Australia
facility: St. Vincent's Hospital Melbourne
city: Sydney
country: Australia
facility: Concord Hospital
city: Sydney
country: Australia
facility: Royal North Shore
city: Sydney
country: Australia
facility: University of Sydney
city: Aalst
country: Belgium
facility: Cardiovascular Center Aalst
city: Montreal
country: Canada
facility: Le'Centre Hospitalier de l'Universite de Montreal
city: Ontario
country: Canada
facility: York PCI Group INC
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
city: Brno
country: Czechia
facility: Masaryk University and University Hospital Brno
city: Copenhagen
country: Denmark
facility: Rigshospitalet University Hospital
city: Lyon
country: France
facility: Cardiovascular Hospital
city: Budapest
country: Hungary
facility: Hungarian Institute of Cardiology
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Klinikos
city: Eindhoven
country: Netherlands
facility: Catharina Hospital Eindhoven
city: The Hague
country: Netherlands
facility: HagaZiekenhuis
city: Zwolle
country: Netherlands
facility: Isala Klinieken
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Danderyds Sjukhus
city: Stockholm
country: Sweden
facility: Karolinska Institutet, Dep of clinical science and education, Södersjukhuset
city: Cardiff
country: United Kingdom
facility: Wales Heart Research Institute
city: Coventry And Warwickshire
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: St. Thomas' Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospital NHS Trust
city: Southhampton
country: United Kingdom
facility: Southampton University Hospitals NHS Trust
Study officials:
affiliation: Stanford University
name: William F Fearon, MD
role: STUDY_CHAIR
affiliation: Catharina Hospital Eindhoven, The Netherlands
name: Nico HJ Pijls, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: VZW Cardiovascular Research Center Aalst
name: Bernard De Bruyne, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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, Casselman F, Witt N, Mavromatis K, Miner SES, Sarma J, Engstrom T, Christiansen EH, Tonino PAL, Reardon MJ, Lu D, Ding VY, Kobayashi Y, Hlatky MA, Mahaffey KW, Desai M, Woo YJ, Yeung AC, Pijls NHJ; FAME 3 Investigators. Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery. N Engl J Med. 2022 Jan 13;386(2):128-137. doi: 10.1056/NEJMoa2112299. Epub 2021 Nov 4.
citation: Piroth Z, Otsuki H, Zimmermann FM, Ferenci T, Keulards DCJ, Yeung AC, Pijls NHJ, De Bruyne B, Fearon WF. Prognostic Value of Measuring Fractional Flow Reserve After Percutaneous Coronary Intervention in Patients With Complex Coronary Artery Disease: Insights From the FAME 3 Trial. Circ Cardiovasc Interv. 2022 Nov;15(11):884-891. doi: 10.1161/CIRCINTERVENTIONS.122.012542. Epub 2022 Sep 19.
citation: Fearon WF, Zimmermann FM, Ding VY, Zelis JM, Piroth Z, Davidavicius G, Mansour S, Kharbanda R, Ostlund-Papadogeorgos N, Oldroyd KG, Wendler O, Reardon MJ, Woo YJ, Yeung AC, Pijls NHJ, De Bruyne B, Desai M, Hlatky MA; FAME 3 Investigators. Quality of Life After Fractional Flow Reserve-Guided PCI Compared With Coronary Bypass Surgery. Circulation. 2022 May 31;145(22):1655-1662. doi: 10.1161/CIRCULATIONAHA.122.060049. Epub 2022 Apr 2.