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

April 10, 2023 updated by: William Fearon, Stanford University

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

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

1500

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Frankston, Australia
        • Peninsula Health
      • Melbourne, Australia
        • St. Vincent's Hospital Melbourne
      • Sydney, Australia
        • Concord Hospital
      • Sydney, Australia
        • Royal North Shore
      • Sydney, Australia
        • University of Sydney
  • Belgium
      • Aalst, Belgium, 9300 Aalst
        • Cardiovascular Center Aalst
  • Canada
      • Montreal, Canada
        • Le'Centre Hospitalier de l'Universite de Montreal
      • Ontario, Canada
        • York PCI Group Inc
      • Ottawa, Canada
        • University of Ottawa Heart Institute
  • Czechia
      • Brno, Czechia
        • Masaryk University and University Hospital Brno
  • Denmark
      • Copenhagen, Denmark
        • Rigshospitalet University Hospital
  • France
      • Lyon, France
        • Cardiovascular Hospital
  • Hungary
      • Budapest, Hungary
        • Hungarian Institute of Cardiology
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Asan Medical Center
  • Lithuania
      • Vilnius, Lithuania
        • Vilnius University Hospital Santariskiu Klinikos
  • Netherlands
      • Eindhoven, Netherlands, 5623 EJ
        • Catharina Hospital Eindhoven
      • The Hague, Netherlands
        • HagaZiekenhuis
      • Zwolle, Netherlands
        • Isala Klinieken
  • New Zealand
      • Hamilton, New Zealand
        • Waikato Hospital
  • Norway
      • Stavanger, Norway
        • Stavanger University Hospital
  • Serbia
      • Belgrade, Serbia
        • University Clinical Center of Serbia
      • Kragujevac, Serbia
        • Clinical Center Kragujevac
  • Sweden
      • Goteborg, Sweden
        • Sahlgrenska University Hospital
      • Stockholm, Sweden
        • Danderyds sjukhus
      • Stockholm, Sweden
        • Karolinska Institutet, Dep of clinical science and education, Södersjukhuset
  • United Kingdom
      • Cardiff, United Kingdom
        • Wales Heart Research Institute
      • Coventry And Warwickshire, United Kingdom
        • University Hospitals Coventry and Warwickshire
      • Glasgow, United Kingdom
        • Golden Jubilee National Hospital
      • London, United Kingdom
        • Kings College Hospital
      • London, United Kingdom
        • St. Thomas' Hospital
      • Manchester, United Kingdom
        • Wythenshawe Hospital
      • Oxford, United Kingdom
        • Oxford University Hospital NHS Trust
      • Southhampton, United Kingdom
        • Southampton University Hospitals NHS Trust
  • United States
    • California
      • Palo Alto, California, United States
        • Palo Alto VA
      • Stanford, California, United States, 94305-2004
        • Stanford University
    • Georgia
      • Decatur, Georgia, United States
        • Atlanta VA Medical Center
    • Illinois
      • Chicago, Illinois, United States
        • Jesse Brown VA Medical Center
    • Kansas
      • Lawrence, Kansas, United States
        • University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States
        • Lexinton VA
      • Lexington, Kentucky, United States
        • University of Kentucky Medical Center
    • Massachusetts
      • Springfield, Massachusetts, United States
        • Baystate Medical Center
    • Minnesota
      • Saint Paul, Minnesota, United States
        • HealthEast St. Joseph's Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Penn Presbyterian Medical Center
    • Tennessee
      • Nashville, Tennessee, United States
        • Centennial Heart
    • Texas
      • Houston, Texas, United States
        • Houston Methodist Hospital
    • Virginia
      • Charlottesville, Virginia, United States
        • University of Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MACCE
Time Frame: 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.
1 year

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

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

Investigators

  • Study Chair: William F Fearon, MD, Stanford University
  • Principal Investigator: Nico HJ Pijls, MD, PhD, Catharina Hospital Eindhoven, The Netherlands
  • Principal Investigator: Bernard De Bruyne, MD, PhD, VZW Cardiovascular Research Center Aalst

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 25, 2014

Primary Completion (Actual)

December 1, 2020

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

March 21, 2014

First Submitted That Met QC Criteria

March 27, 2014

First Posted (Estimate)

April 1, 2014

Study Record Updates

Last Update Posted (Actual)

May 8, 2023

Last Update Submitted That Met QC Criteria

April 10, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FAME 3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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