Coronary ArteriosclerosisNCT00267774
Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (F.A.M.E.)
A study testing Fractional flow reserve and Angio-guided PCI in people with Coronary Arteriosclerosis, run by Stanford University at 2 sites in 2 countries.
Trial summary
In this multicenter, international study we are evaluating two approaches to determine which coronary artery narrowings require stent placement in patients with multivessel coronary artery disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Arteriosclerosis
- What is being tested?
- Fractional flow reserve and Angio-guided PCI
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,005 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jan 2006to Sep 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria:- at least 2 coronary lesions of 50% stenosis or greater in at least 2 major epicardial arteries
- age>/=18
Exclusion Criteria:-- STEMI < 5 days ago or non-STEMI with CK > 1000 U/l < 5 days ago
- Pregnancy
- Extremely tortuous or calcified coronary arteries, or other technical conditions interfering with reliable coronary pressure measurement
- Serious concomitant disease, decreasing life expectancy to <2 years
- Previous coronary bypass surgery (CABG)
- Contraindication for drug-eluting stent
- Cardiogenic shock
- Inability to give informed consent
- Suspicion of significant left main (LM) stenosis
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
In this multicenter, international study we are evaluating two approaches to determine which coronary artery narrowings require stent placement in patients with multivessel coronary artery disease. Patients will be randomized to an angiographic strategy, where only coronary angiography is used to determine which lesions to stent or to a pressure wire strategy where fractional flow reserve, an index measured with the pressure wire, will be used to determine which lesions to stent. The primary outcome will be major adverse cardiac events at 1 year. A secondary outcome will be cost-effectiveness.
Read the detailed description
Detailed protocol
- If a patient is eligible for the study (see inclusion and exclusion criteria) and has given informed consent, the operator has to define all lesions with a stenosis severity of at least 50% by visual estimate in which he would consider stent implantation. These stenoses are noted on a scheme of the coronary arteries before randomization.
- Thereafter, randomization is performed to the FFR-guided strategy or the angiography-guided strategy. If the patient is randomized to the angiography-guided strategy, all the lesions indicated beforehand, will be stented with drug-eluting stents. If the patient is assigned to the FFR-guided group, fractional flow reserve is measured in all lesions and only those lesions are stented with a fractional flow reserve </=0.80. Treatment after PCI is according to local routine and should include at least aspirin 80 mg daily and clopidogrel (Plavix) 75 mg per day for at least 12months.
- FFR should be determined by using i.v. adenosine 140 µg/kg/min, in order to make pull-back recordings and analyze different abnormalities along the coronary arteries. Adenosine i.v. by the femoral venous route, is mandatory for participation in the study.
- In case of serial stenosis, FFR 'of the complete vessel' should be </= 0.80 to warrant PCI of one of more of these lesions in case the patient belongs to the FFR-guided group. In case of the angio-guided group, every lesion >50% by visual estimation that the operator indicated a prior as requiring stenting, should be stented (this is mandatory). Long stents to cover a segment or multiple shorter stents, can be placed at the discretion of the operator.
Follow-up
All patients will be followed up after 1 month (±1 week), 6 months (±1 month), and 1 year (±1 month). All adverse cardiac events (death, acute MI, CABG or [re]-PCI will be noted, as well as functional class and number of anti-anginal drugs. If a patient is admitted to a hospital because of an acute coronary syndrome, repeat angiography is strongly advocated to define if the event is related to one of the deferred lesions or to one of the non-deferred lesions. If the patient belongs to the FFR-guided arm, repeat measurement of FFR is advocated for all lesions. If, during follow-up, patients in the FFR-guided group have to undergo coronary angiography because of recurrent angina or any other reason without an event, pressure measurement should be repeated as well.
On the contrary, once a patient has been assigned to the angiographic guided group, this strategy should be followed consistently during follow-up investigations. For example, if a patient in the angiographic guided arm has recurrent chest pain, undergoes angiography, and is found to have in-stent restenosis, re-PCI should be performed based on the angiogram and pressure wire use is prohibited.
In other words, the strategy to which the patient has been assigned initially, should be followed during the entire study period.
Endpoints
Primary endpoints
- The primary clinical endpoint is the 12-month binary major adverse cardiac event (MACE) rate. MACE is defined as:
- All cause death,
- Documented myocardial infarction,
- Repeat revascularization (PCI and/or CABG) as adjudicated by the Clinical Event Committee
Secondary endpoints
- Global cost effectiveness after one year
- Cardiac death and myocardial infarction rate at 1 year
- Functional class at 1 year.
- Number of anti-anginal drugs after 1 year
- Overall MACE rate at 1 month post-procedure and at 6 months, 2, 3 and 5 years.
- A comparison of outcomes based on type of drug-eluting stent.
- Prognostic value of FFR after stenting.
- Correlation between FFR and nuclear perfusion imaging.
- Conditions
- Coronary Arteriosclerosis
- Being tested
- Fractional flow reserve, Angio-guided PCI
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fractional flow reserveDevice
Angio-guided PCIProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| FFR guided PCI | Experimental | Not described Receives: Device: Fractional flow reserve |
| Angio-guided PCI | Active comparator | Not described Receives: Procedure: Angio-guided PCI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Adverse Cardiac Events
All cause death, Documented myocardial infarction, Repeat revascularization (PCI and/or CABG) as adjudicated by the Clinical Event Committee
Measured: 1 year
Secondary outcomes (1)
Cost Effectiveness Measured as Index Procedural and Hospitalization Costs
Costs for each strategy included the initial procedural costs and costs during the 1-year follow-up. The costs of the index procedures were calculated from the actual resource consumption by determining the amount of guiding catheters, regular wires, pressure wires, balloon dilatation catheters, stents, antiplatelet therapy, adenosine, contrast media, and hospital days used for each patient's index procedure. These were multiplied by the cost of each resource in US dollars. All costs were converted to 2008 US dollars using the consumer price index (www.bls.gov).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2005 (estimated)
- Study startJan 2006
- Primary completionSep 2008
- Study completionSep 2015
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 (7)Papers the sponsor has linked to this study.
- Other trials for Coronary ArteriosclerosisStudies 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
- 1,005 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William Fearon, Stanford University
- Investigators
- Nico H Pijls, Principal investigator, Catharina Ziekenhuis EindhovenWilliam F Fearon, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00267774
- Sponsor's protocol ID
- 3933
- Status last verified
- Oct 2017
- First submitted
- 19 Dec 2005
- Last updated
- 13 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Fearon WF, Bornschein B, Tonino PA, Gothe RM, Bruyne BD, Pijls NH, Siebert U; Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) Study Investigators. Economic evaluation of fractional flow reserve-guided percutaneous coronary intervention in patients with multivessel disease. Circulation. 2010 Dec 14;122(24):2545-50. doi: 10.1161/CIRCULATIONAHA.109.925396. Epub 2010 Nov 29.
PubMed 21126973Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009 Jan 15;360(3):213-24. doi: 10.1056/NEJMoa0807611.
PubMed 19144937Nishi T, Piroth Z, De Bruyne B, Jagic N, Mobius-Winkler S, Kobayashi Y, Derimay F, Fournier S, Barbato E, Tonino P, Juni P, Pijls NHJ, Fearon WF. Fractional Flow Reserve and Quality-of-Life Improvement After Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease. Circulation. 2018 Oct 23;138(17):1797-1804. doi: 10.1161/CIRCULATIONAHA.118.035263.
PubMed 30354650Kobayashi Y, Nam CW, Tonino PA, Kimura T, De Bruyne B, Pijls NH, Fearon WF; FAME Study Investigators. The Prognostic Value of Residual Coronary Stenoses After Functionally Complete Revascularization. J Am Coll Cardiol. 2016 Apr 12;67(14):1701-11. doi: 10.1016/j.jacc.2016.01.056.
PubMed 27056776van Nunen LX, Zimmermann FM, Tonino PA, Barbato E, Baumbach A, Engstrom T, Klauss V, MacCarthy PA, Manoharan G, Oldroyd KG, Ver Lee PN, Van't Veer M, Fearon WF, De Bruyne B, Pijls NH; FAME Study Investigators. Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet. 2015 Nov 7;386(10006):1853-60. doi: 10.1016/S0140-6736(15)00057-4. Epub 2015 Aug 30.
PubMed 26333474Nam CW, Mangiacapra F, Entjes R, Chung IS, Sels JW, Tonino PA, De Bruyne B, Pijls NH, Fearon WF; FAME Study Investigators. Functional SYNTAX score for risk assessment in multivessel coronary artery disease. J Am Coll Cardiol. 2011 Sep 13;58(12):1211-8. doi: 10.1016/j.jacc.2011.06.020.
PubMed 21903052Pijls NH, Fearon WF, Tonino PA, Siebert U, Ikeno F, Bornschein B, van't Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, De Bruyne B; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study. J Am Coll Cardiol. 2010 Jul 13;56(3):177-84. doi: 10.1016/j.jacc.2010.04.012. Epub 2010 May 28.
PubMed 20537493
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (F.A.M.E.)
- ClinicalTrials.gov ID
- NCT00267774
- Acronym / sponsor ID
- 3933
- Conditions
- Coronary Arteriosclerosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,005 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Jan 2006
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 21 Dec 2005 (estimated)
- Results
- Posted 27 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this multicenter, international study we are evaluating two approaches to determine which coronary artery narrowings require stent placement in patients with multivessel coronary artery disease. Patients will be randomized to an angiographic strategy, where only coronary angiography is used to determine which lesions to stent or to a pressure wire strategy where fractional flow reserve, an index measured with the pressure wire, will be used to determine which lesions to stent. The primary outcome will be major adverse cardiac events at 1 year. A secondary outcome will be cost-effectiveness.
Detailed description
Detailed protocol
- If a patient is eligible for the study (see inclusion and exclusion criteria) and has given informed consent, the operator has to define all lesions with a stenosis severity of at least 50% by visual estimate in which he would consider stent implantation. These stenoses are noted on a scheme of the coronary arteries before randomization.
- Thereafter, randomization is performed to the FFR-guided strategy or the angiography-guided strategy. If the patient is randomized to the angiography-guided strategy, all the lesions indicated beforehand, will be stented with drug-eluting stents. If the patient is assigned to the FFR-guided group, fractional flow reserve is measured in all lesions and only those lesions are stented with a fractional flow reserve </=0.80. Treatment after PCI is according to local routine and should include at least aspirin 80 mg daily and clopidogrel (Plavix) 75 mg per day for at least 12months.
- FFR should be determined by using i.v. adenosine 140 µg/kg/min, in order to make pull-back recordings and analyze different abnormalities along the coronary arteries. Adenosine i.v. by the femoral venous route, is mandatory for participation in the study.
- In case of serial stenosis, FFR 'of the complete vessel' should be </= 0.80 to warrant PCI of one of more of these lesions in case the patient belongs to the FFR-guided group. In case of the angio-guided group, every lesion >50% by visual estimation that the operator indicated a prior as requiring stenting, should be stented (this is mandatory). Long stents to cover a segment or multiple shorter stents, can be placed at the discretion of the operator.
Follow-up
All patients will be followed up after 1 month (±1 week), 6 months (±1 month), and 1 year (±1 month). All adverse cardiac events (death, acute MI, CABG or [re]-PCI will be noted, as well as functional class and number of anti-anginal drugs. If a patient is admitted to a hospital because of an acute coronary syndrome, repeat angiography is strongly advocated to define if the event is related to one of the deferred lesions or to one of the non-deferred lesions. If the patient belongs to the FFR-guided arm, repeat measurement of FFR is advocated for all lesions. If, during follow-up, patients in the FFR-guided group have to undergo coronary angiography because of recurrent angina or any other reason without an event, pressure measurement should be repeated as well.
On the contrary, once a patient has been assigned to the angiographic guided group, this strategy should be followed consistently during follow-up investigations. For example, if a patient in the angiographic guided arm has recurrent chest pain, undergoes angiography, and is found to have in-stent restenosis, re-PCI should be performed based on the angiogram and pressure wire use is prohibited.
In other words, the strategy to which the patient has been assigned initially, should be followed during the entire study period.
Endpoints
Primary endpoints
- The primary clinical endpoint is the 12-month binary major adverse cardiac event (MACE) rate. MACE is defined as:
- All cause death,
- Documented myocardial infarction,
- Repeat revascularization (PCI and/or CABG) as adjudicated by the Clinical Event Committee
Secondary endpoints
- Global cost effectiveness after one year
- Cardiac death and myocardial infarction rate at 1 year
- Functional class at 1 year.
- Number of anti-anginal drugs after 1 year
- Overall MACE rate at 1 month post-procedure and at 6 months, 2, 3 and 5 years.
- A comparison of outcomes based on type of drug-eluting stent.
- Prognostic value of FFR after stenting.
- Correlation between FFR and nuclear perfusion imaging.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FFR guided PCI | Experimental | Device: Fractional flow reserve |
| Angio-guided PCI | Active comparator | Procedure: Angio-guided PCI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fractional flow reserve | Device | FFR guided PCI |
| Angio-guided PCI | Procedure or surgery | Angio-guided PCI |
Primary outcome
Major Adverse Cardiac Events
Time frame: 1 year
All cause death, Documented myocardial infarction, Repeat revascularization (PCI and/or CABG) as adjudicated by the Clinical Event Committee
1 secondary outcome
Cost Effectiveness Measured as Index Procedural and Hospitalization Costs
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21126973Fearon WF, Bornschein B, Tonino PA, Gothe RM, Bruyne BD, Pijls NH, Siebert U; Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) Study Investigators. Economic evaluation of fractional flow reserve-guided percutaneous coronary intervention in patients with multivessel disease. Circulation. 2010 Dec 14;122(24):2545-50. doi: 10.1161/CIRCULATIONAHA.109.925396. Epub 2010 Nov 29.
- Results publication: PubMed 19144937Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009 Jan 15;360(3):213-24. doi: 10.1056/NEJMoa0807611.
- Derived from this study: PubMed 30354650Nishi T, Piroth Z, De Bruyne B, Jagic N, Mobius-Winkler S, Kobayashi Y, Derimay F, Fournier S, Barbato E, Tonino P, Juni P, Pijls NHJ, Fearon WF. Fractional Flow Reserve and Quality-of-Life Improvement After Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease. Circulation. 2018 Oct 23;138(17):1797-1804. doi: 10.1161/CIRCULATIONAHA.118.035263.
- Derived from this study: PubMed 27056776Kobayashi Y, Nam CW, Tonino PA, Kimura T, De Bruyne B, Pijls NH, Fearon WF; FAME Study Investigators. The Prognostic Value of Residual Coronary Stenoses After Functionally Complete Revascularization. J Am Coll Cardiol. 2016 Apr 12;67(14):1701-11. doi: 10.1016/j.jacc.2016.01.056.
- Derived from this study: PubMed 26333474van Nunen LX, Zimmermann FM, Tonino PA, Barbato E, Baumbach A, Engstrom T, Klauss V, MacCarthy PA, Manoharan G, Oldroyd KG, Ver Lee PN, Van't Veer M, Fearon WF, De Bruyne B, Pijls NH; FAME Study Investigators. Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet. 2015 Nov 7;386(10006):1853-60. doi: 10.1016/S0140-6736(15)00057-4. Epub 2015 Aug 30.
- Derived from this study: PubMed 21903052Nam CW, Mangiacapra F, Entjes R, Chung IS, Sels JW, Tonino PA, De Bruyne B, Pijls NH, Fearon WF; FAME Study Investigators. Functional SYNTAX score for risk assessment in multivessel coronary artery disease. J Am Coll Cardiol. 2011 Sep 13;58(12):1211-8. doi: 10.1016/j.jacc.2011.06.020.
- Derived from this study: PubMed 20537493Pijls NH, Fearon WF, Tonino PA, Siebert U, Ikeno F, Bornschein B, van't Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, De Bruyne B; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study. J Am Coll Cardiol. 2010 Jul 13;56(3):177-84. doi: 10.1016/j.jacc.2010.04.012. Epub 2010 May 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nico H Pijls principal investigator
Catharina Ziekenhuis Eindhoven
William F Fearon principal investigator
Stanford University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fractional flow reserve and Angio-guided PCI in people with Coronary Arteriosclerosis, run by Stanford University at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Adverse Cardiac Events (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00267774, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.