Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (F.A.M.E.)

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00267774
• Collaborator: (none)
• Enrollment: 1,005
• Locations: 2
• Arms: 2
• Duration (Months): 116
• Patients Per Site: 502.5
• Patients Per Site Per Month: 4.3

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Arteriosclerosis	Device: Fractional flow reserve; Procedure: Angio-guided PCI	N/A

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

1. 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

1. Global cost effectiveness after one year

2. Cardiac death and myocardial infarction rate at 1 year

3. Functional class at 1 year.

4. Number of anti-anginal drugs after 1 year

5. Overall MACE rate at 1 month post-procedure and at 6 months, 2, 3 and 5 years.

6. A comparison of outcomes based on type of drug-eluting stent.

7. Prognostic value of FFR after stenting.

8. Correlation between FFR and nuclear perfusion imaging.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1005 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FFR guided PCI	Device: Fractional flow reserve
Active Comparator: Angio-guided PCI	Procedure: Angio-guided PCI

Outcome Measures

Primary Outcome Measures

1. Major Adverse Cardiac Events [1 year]

   All cause death, Documented myocardial infarction, Repeat revascularization (PCI and/or CABG) as adjudicated by the Clinical Event Committee

Secondary Outcome Measures

1. Cost Effectiveness Measured as Index Procedural and Hospitalization Costs [1 year]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305
2	Catharina Hospital	Eindhoven		Netherlands

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Nico H Pijls, Catharina Ziekenhuis Eindhoven
• Principal Investigator: William F Fearon, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: William Fearon, Principle Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT00267774
• Other Study ID Numbers: 3933
• First Posted: Dec 21, 2005
• Last Update Posted: Nov 13, 2017
• Last Verified: Oct 1, 2017

• Additional relevant MeSH terms: Arteriosclerosis; Coronary Artery Disease; Myocardial Ischemia

Study Results

Participant Flow

Arm/Group Title	FFR Guided PCI	Angio-guided PCI
Arm/Group Description	Fractional flow reserve	Angio-guided PCI
Period Title: Overall Study
STARTED	509	496
COMPLETED	509	496
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	FFR Guided PCI	Angio-guided PCI	Total
Arm/Group Description	Fractional flow reserve	Angio-guided PCI	Total of all reporting groups
Overall Participants	509	496	1005
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.6 (10.3)	64.2 (10.2)	64.4 (10.3)
Sex: Female, Male (Count of Participants)
Female	125 24.6%	136 27.4%	261 26%
Male	384 75.4%	360 72.6%	744 74%

Outcome Measures

1. Primary Outcome

Title	Major Adverse Cardiac Events
Description	All cause death, Documented myocardial infarction, Repeat revascularization (PCI and/or CABG) as adjudicated by the Clinical Event Committee
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FFR Guided PCI	Angio-guided PCI
Arm/Group Description	Fractional flow reserve	Angio-guided PCI
Measure Participants	509	496
Number [participants]	67 13.2%	91 18.3%

2. Secondary Outcome

Title	Cost Effectiveness Measured as Index Procedural and Hospitalization Costs
Description	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).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FFR Guided PCI	Angio-guided PCI
Arm/Group Description	Fractional flow reserve	Angio-guided PCI
Measure Participants	509	496
Mean (Standard Deviation) [US dollars]	13,182 (9667)	14,878 (9509)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FFR Guided PCI, Angio-guided PCI
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	A 2-sided value of P<0.05 was considered to indicate statistical significance.
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Per protocol, major cardiac events were collected as adverse events.
Arm/Group Title	FFR Guided PCI		Angio-guided PCI
Arm/Group Description	Fractional flow reserve		Angio-guided PCI
All Cause Mortality
	FFR Guided PCI		Angio-guided PCI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	FFR Guided PCI		Angio-guided PCI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/509 (13.2%)		91/496 (18.3%)
Cardiac disorders
Death	9/509 (1.8%)		15/496 (3%)
Myocardial infarction	29/509 (5.7%)		43/496 (8.7%)
Repeat vascularization	33/509 (6.5%)		47/496 (9.5%)
Other (Not Including Serious) Adverse Events
	FFR Guided PCI		Angio-guided PCI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/509 (0%)		0/496 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.