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

Not Applicable

Active, not recruiting

• Conditions: Coronary Disease; Coronary Stenosis
• Interventions: Procedure: FFR guided PCI; Procedure: CABG; Device: Resolute Integrity Stent; Device: Resolute Onyx Stent

• Registration Number: NCT02100722
• Lead Sponsor: Stanford University

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.

Study Timeline

• Study First Submitted: 2014-03-21
• Study First Submitted QC: 2014-03-27
• Study First Posted: 2014-04-01
• Study Start: 2014-08-25
• Primary Completion: 2020-12-01
• Results First Submitted: 2021-11-24
• Results First Submitted QC: 2021-12-21
• Results First Posted: 2022-01-20
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-16
• Last Update Posted: 2024-04-18
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1500

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FFR guided PCI	FFR guided PCI	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 (or Onyx) drug-eluting stent (DES) as per usual routine. If the FFR is \>0.80 then PCI will be deferred. Only those sites with prior experience measuring FFR will be included in the FAME 3 trial. These patients in whom FFR of a particular lesion was not possible will be included in all analyses based on the intention to treat principle.
FFR guided PCI	Resolute Integrity Stent	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 (or Onyx) drug-eluting stent (DES) as per usual routine. If the FFR is \>0.80 then PCI will be deferred. Only those sites with prior experience measuring FFR will be included in the FAME 3 trial. These patients in whom FFR of a particular lesion was not possible will be included in all analyses based on the intention to treat principle.
FFR guided PCI	Resolute Onyx Stent	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 (or Onyx) drug-eluting stent (DES) as per usual routine. If the FFR is \>0.80 then PCI will be deferred. Only those sites with prior experience measuring FFR will be included in the FAME 3 trial. These patients in whom FFR of a particular lesion was not possible will be included in all analyses based on the intention to treat principle.
CABG	CABG	CABG will be performed as per clinical routine at each participating center. Both off-pump and on-pump surgery are acceptable, as long as the surgeon and the site are experienced in the particular technique. An internal mammary graft to the LAD should be attempted in all cases, if feasible. Complete arterial revascularization is strongly recommended, however, each center should use a conduit strategy with which they are most comfortable. All vessels ≥ 1,5 mm in diameter and with ≥ 50% stenosis should be bypassed, if technically feasible.

Primary Outcome Measures

Name	Time	Method
MACCE	1 year	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.

Secondary Outcome Measures

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

Trial Locations

Locations (46)

Jesse Brown VA Medical Center; 🇺🇸 Chicago, Illinois, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

Palo Alto VA; 🇺🇸 Palo Alto, California, United States

Atlanta VA Medical Center; 🇺🇸 Decatur, Georgia, United States

Stanford University; 🇺🇸 Stanford, California, United States

HealthEast St. Joseph's Hospital; 🇺🇸 Saint Paul, Minnesota, United States

Lexinton VA; 🇺🇸 Lexington, Kentucky, United States

University of Kentucky Medical Center; 🇺🇸 Lexington, Kentucky, United States

Penn Presbyterian Medical Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Peninsula Health; 🇦🇺 Frankston, Australia

St. Vincent's Hospital Melbourne; 🇦🇺 Melbourne, Australia

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Concord Hospital; 🇦🇺 Sydney, Australia

Royal North Shore; 🇦🇺 Sydney, Australia

University of Sydney; 🇦🇺 Sydney, Australia

Cardiovascular Center Aalst; 🇧🇪 Aalst, Belgium

University of Ottawa Heart Institute; 🇨🇦 Ottawa, Canada

Masaryk University and University Hospital Brno; 🇨🇿 Brno, Czechia

Le'Centre Hospitalier de l'Universite de Montreal; 🇨🇦 Montreal, Canada

Isala Klinieken; 🇳🇱 Zwolle, Netherlands

Hungarian Institute of Cardiology; 🇭🇺 Budapest, Hungary

Cardiovascular Hospital; 🇫🇷 Lyon, France

Vilnius University Hospital Santariskiu Klinikos; 🇱🇹 Vilnius, Lithuania

Catharina Hospital Eindhoven; 🇳🇱 Eindhoven, Netherlands

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

HagaZiekenhuis; 🇳🇱 The Hague, Netherlands

Waikato Hospital; 🇳🇿 Hamilton, New Zealand

Sahlgrenska University Hospital; 🇸🇪 Goteborg, Sweden

University Hospitals Coventry and Warwickshire; 🇬🇧 Coventry And Warwickshire, United Kingdom

Wales Heart Research Institute; 🇬🇧 Cardiff, United Kingdom

Karolinska Institutet, Dep of clinical science and education, Södersjukhuset; 🇸🇪 Stockholm, Sweden

Danderyds Sjukhus; 🇸🇪 Stockholm, Sweden

Golden Jubilee National Hospital; 🇬🇧 Glasgow, United Kingdom

Kings College Hospital; 🇬🇧 London, United Kingdom

Wythenshawe Hospital; 🇬🇧 Manchester, United Kingdom

St. Thomas' Hospital; 🇬🇧 London, United Kingdom

Southampton University Hospitals NHS Trust; 🇬🇧 Southhampton, United Kingdom

Oxford University Hospital NHS Trust; 🇬🇧 Oxford, United Kingdom

Baystate Medical Center; 🇺🇸 Springfield, Massachusetts, United States

Clinical Center Kragujevac; 🇷🇸 Kragujevac, Serbia

Stavanger University Hospital; 🇳🇴 Stavanger, Norway

University Clinical Center of Serbia; 🇷🇸 Belgrade, Serbia

Centennial Heart; 🇺🇸 Nashville, Tennessee, United States

York PCI Group INC; 🇨🇦 Ontario, Canada

Rigshospitalet University Hospital; 🇩🇰 Copenhagen, Denmark

University of Kansas Medical Center; 🇺🇸 Lawrence, Kansas, United States