Coronary DiseaseFAME 3NCT02100722
A Comparison of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Patients With Multivessel Coronary Artery Disease
A study testing FFR guided PCI, CABG and Resolute Integrity Stent in people with Coronary Disease and Coronary Stenosis, run by Stanford University at 46 sites in 16 countries.
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… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Coronary Disease, Coronary Stenosis
- What is being tested?
- FFR guided PCI, CABG and Resolute Integrity Stent
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,500 participants
- Where
- 46 sitesin 16 countries
- Study dates
- 25 Aug 2014to 1 Dec 2024
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
46 sites in 16 countries.
46 sites in 16 countries
United States13 sites
University of Virginia
Charlottesville, Virginia
Jesse Brown VA Medical Center
Chicago, Illinois
Atlanta VA Medical Center
Decatur, Georgia
Houston Methodist Hospital
Houston, Texas
University of Kansas Medical Center
Lawrence, Kansas
Lexinton VA
Lexington, Kentucky
University of Kentucky Medical Center
Lexington, Kentucky
Centennial Heart
Nashville, Tennessee
Palo Alto VA
Palo Alto, California
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania
HealthEast St. Joseph's Hospital
Saint Paul, Minnesota
Baystate Medical Center
Springfield, Massachusetts
Stanford University
Stanford, California, 94305-2004
United Kingdom8 sites
Wales Heart Research Institute
Cardiff
University Hospitals Coventry and Warwickshire
Coventry and Warwickshire
Golden Jubilee National Hospital
Glasgow
Kings College Hospital
London
St. Thomas' Hospital
London
Wythenshawe Hospital
Manchester
Oxford University Hospital NHS Trust
Oxford
Southampton University Hospitals NHS Trust
Southhampton
Australia5 sites
Peninsula Health
Frankston
St. Vincent's Hospital Melbourne
Melbourne
Concord Hospital
Sydney
Royal North Shore
Sydney
University of Sydney
Sydney
Canada3 sites
Le'Centre Hospitalier de l'Universite de Montreal
Montreal
York PCI Group INC
Ontario
University of Ottawa Heart Institute
Ottawa
Netherlands3 sites
Catharina Hospital Eindhoven
Eindhoven, 5623 EJ
HagaZiekenhuis
The Hague
Isala Klinieken
Zwolle
Sweden3 sites
Sahlgrenska University Hospital
Gothenburg
Danderyds Sjukhus
Stockholm
Karolinska Institutet, Dep of clinical science and education, Södersjukhuset
Stockholm
Serbia2 sites
University Clinical Center of Serbia
Belgrade
Clinical Center Kragujevac
Kragujevac
About this study
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
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).
Read the 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.
- Conditions
- Coronary Disease, Coronary Stenosis
- Being tested
- FFR guided PCI, CABG, Resolute Integrity Stent, Resolute Onyx Stent
- Medical subject headings
- Coronary Disease, Coronary Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FFR guided PCIProcedure or surgery
Also called Fractional Flow Reserve-Guided PCI
CABGProcedure or surgery
Coronary Artery Bypass Graft Surgery (CABG)
Resolute Integrity StentDevice
Durable polymer zotarolimus-eluting stent
Resolute Onyx StentDevice
Durable polymer zotarolimus-eluting stent
| Study group | Role | What they receive |
|---|---|---|
| FFR guided PCI | Active comparator | 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. Receives: Procedure: FFR guided PCI; Device: Resolute Integrity Stent; Device: Resolute Onyx Stent |
| CABG | Active comparator | 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. Receives: Procedure: CABG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (16)
Key Secondary Outcome: Composite of Death From Any Cause, Myocardial Infarction, or Stroke
Death, MI, or stroke at 3-year follow-up
Measured: 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.
Measured: 1 year
Death
Death evaluated excluding patients lost to follow-up from each arm
Measured: 1 year
Number of Participants Experiencing Myocardial Infarction
MI evaluated excluding patients lost to follow-up from each arm
Measured: 1 year
Number of Participants Experiencing Stroke
Stroke evaluated excluding patients lost to follow-up from each arm.
Measured: 1 year
Number of Participants Requiring Repeat Revascularization
Any repeat revascularization evaluated excluding patients lost to follow-up from each arm
Measured: 1 year
Number of Participants Experiencing BARC Type 3-5 Bleeding
Bleeding Academic Research Consortium (BARC) type 3-5 indicates severe bleeding.
Measured: 1 year
Number of Participants Experiencing Acute Kidney Injury
Measured: 1 year
Number of Participants Experiencing Atrial Fibrillation or Clinically Significant Arrhythmia
Measured: 1 year
Number of Participants Experiencing Definite Stent Thrombosis
Measured: 1 year
Number of Participants Experiencing Definite Symptomatic Graft Occlusion
Measured: 1 year
Number of Participants Requiring Rehospitalization Within 30 Days
Measured: 30 days
MACCE
Death, MI, stroke and any repeat revascularization (MACCE) rate at 5 years
Measured: 5 years
Death, MI, or Stroke at 5 Years
Death, MI, or stroke at 5 years
Measured: 5 years
Individual Components of Primary Outcome
Individual components of primary outcome: number of participants experiencing death, myocardial infarction, and stroke
Measured: At year 3
Individual Components of Primary Outcome
Individual components of primary outcome: number of participants experiencing death, myocardial infarction, and stroke
Measured: At year 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2014 (estimated)
- Study start25 Aug 2014
- Primary completion1 Dec 2020
- Study completion1 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Coronary DiseaseStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- VZW Cardiovascular Research Center Aalst, Catharina Ziekenhuis Eindhoven, Golden Jubilee National Hospital, University of California, Irvine, Medtronic, Abbott Medical Devices, Genae, King's College Hospital NHS Trust, Houston Methodist DeBakey Heart & Vascular Center
- Responsible party
- Principal investigator, William Fearon, Stanford University
- Investigators
- William F Fearon, MD, Study chair, Stanford UniversityNico HJ Pijls, MD, PhD, Principal investigator, Catharina Hospital Eindhoven, The NetherlandsBernard De Bruyne, MD, PhD, Principal investigator, VZW Cardiovascular Research Center Aalst
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02100722
- Sponsor's protocol ID
- FAME 3
- Acronym
- FAME 3
- Status last verified
- Mar 2025
- First submitted
- 21 Mar 2014
- Last updated
- 7 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 26386784Zimmermann 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.
PubMed 31207442Fearon 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.
PubMed 34735046Fearon WF, Zimmermann FM, Ding VY, Takahashi K, 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, Otsuki H, Kobayashi Y, Hlatky MA, Mahaffey KW, Desai M, Woo YJ, Yeung AC, Pijls NHJ, De Bruyne B. Outcomes after fractional flow reserve-guided percutaneous coronary intervention versus coronary artery bypass grafting (FAME 3): 5-year follow-up of a multicentre, open-label, randomised trial. Lancet. 2025 Apr 26;405(10488):1481-1490. doi: 10.1016/S0140-6736(25)00505-7. Epub 2025 Mar 30.
PubMed 40174598Takahashi K, Otsuki H, Zimmermann FM, Ding VY, Piroth Z, Oldroyd KG, Wendler O, Reardon MJ, Desai M, Woo YJ, Yeung AC, De Bruyne B, Pijls NHJ, Fearon WF; FAME 3 Trial Investigators. Outcomes After CABG Compared With FFR-Guided PCI in Patients Presenting With Acute Coronary Syndrome. JACC Cardiovasc Interv. 2025 Apr 14;18(7):838-848. doi: 10.1016/j.jcin.2025.01.434.
PubMed 40240081Takahashi K, Otsuki H, Zimmermann FM, Ding VY, Engstrom T, Horsted Thyregod HG, Beleslin B, Putnik S, Tapp L, Barker T, Redwood S, Young C, Bech GJ, Hoohenkerk GJF, De Bruyne B, Pijls NHJ, Fearon WF; FAME 3 Trial Investigators. FFR-Guided Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting in Patients With Diabetes. JAMA Cardiol. 2025 Jun 1;10(6):603-608. doi: 10.1001/jamacardio.2025.0095.
PubMed 40072460Takahashi K, Otsuki H, Zimmermann FM, Ding VY, Oldroyd KG, Wendler O, Reardon MJ, Woo YJ, Yeung AC, Pijls NHJ, De Bruyne B, Fearon WF; FAME 3 Trial Investigators. Sex Differences in Patients Undergoing FFR-Guided PCI or CABG in the FAME 3 Trial. JACC Cardiovasc Interv. 2025 Jan 27;18(2):157-167. doi: 10.1016/j.jcin.2024.09.030. Epub 2024 Dec 4.
PubMed 39641725Otsuki H, Takahashi K, Zimmermann FM, Mavromatis K, Aminian A, Jagic N, Dambrink JE, Kala P, MacCarthy P, Witt N, Kobayashi Y, Takahashi T, Woo YJ, Yeung AC, De Bruyne B, Pijls NHJ, Fearon WF; FAME 3 Trial Investigators. Impact of a Chronic Total Occlusion on Outcomes After FFR-Guided PCI or Coronary Bypass Surgery: A FAME 3 Substudy. Circ Cardiovasc Interv. 2024 Nov;17(11):e014300. doi: 10.1161/CIRCINTERVENTIONS.124.014300. Epub 2024 Nov 6.
PubMed 39502029Zimmermann FM, Ding VY, Pijls NHJ, 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, Otsuki H, Kobayashi Y, Hlatky MA, Mahaffey KW, Desai M, Woo YJ, Yeung AC, De Bruyne B, Fearon WF; FAME 3 Investigators. Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial. Circulation. 2023 Sep 19;148(12):950-958. doi: 10.1161/CIRCULATIONAHA.123.065770. Epub 2023 Aug 21.
PubMed 37602376Piroth 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.
PubMed 36121706Fearon 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.
PubMed 35369704