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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Coronary Disease, Coronary Stenosis

Intervention / Treatment
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* Procedure: FFR guided PCI
* Procedure: CABG
* Device: Resolute Integrity Stent
* Device: Resolute Onyx Stent


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FFR guided PCI<br>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. | Procedure: FFR guided PCI<br> <br> * Other names: Fractional Flow Reserve-Guided PCI;Device: Resolute Integrity Stent<br>* Durable polymer zotarolimus-eluting stent<br>Device: Resolute Onyx Stent<br>* Durable polymer zotarolimus-eluting stent<br>|
| Active Comparator: CABG<br>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. | Procedure: CABG<br>* Coronary Artery Bypass Graft Surgery (CABG)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key Secondary Outcome: Composite of Death From Any Cause, Myocardial Infarction, or Stroke | Death, MI, or stroke at 3-year follow-up | 3 years | 
| 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 | 
| Death | Death evaluated excluding patients lost to follow-up from each arm | 1 year | 
| Number of Participants Experiencing Myocardial Infarction | MI evaluated excluding patients lost to follow-up from each arm | 1 year | 
| Number of Participants Experiencing Stroke | Stroke evaluated excluding patients lost to follow-up from each arm. | 1 year | 
| Number of Participants Requiring Repeat Revascularization | Any repeat revascularization evaluated excluding patients lost to follow-up from each arm | 1 year | 
| Number of Participants Experiencing BARC Type 3-5 Bleeding | Bleeding Academic Research Consortium (BARC) type 3-5 indicates severe bleeding. | 1 year | 
| Number of Participants Experiencing Acute Kidney Injury |  | 1 year | 
| Number of Participants Experiencing Atrial Fibrillation or Clinically Significant Arrhythmia |  | 1 year | 
| Number of Participants Experiencing Definite Stent Thrombosis |  | 1 year | 
| Number of Participants Experiencing Definite Symptomatic Graft Occlusion |  | 1 year | 
| Number of Participants Requiring Rehospitalization Within 30 Days |  | 30 days | 
| MACCE | Death, MI, stroke and any repeat revascularization (MACCE) rate at 2 years, 3 years and 5 years | 2 years, 3 years, 5 years | 
| Death, MI, or Stroke at 5 Years | Death, MI, or stroke at 5 years | 5 years | 
| Individual Components of Primary Outcome | Individual components of primary outcome | 3 years, 5 years |