Fractional Flow Reserve Versus Angiographically Guided Management to Optimise Outcomes in Unstable Coronary Syndromes (FAMOUS NSTEMI)
Background: In patients with acute non-ST elevation myocardial infarction (NSTEMI) coronary arteriography is usually recommended however visual interpretation of the coronary angiogram is subjective. A complementary diagnostic approach involves measuring the pressure drop across a coronary stenosis (fractional flow reserve, FFR) with a pressure-sensitive guidewire.
Hypothesis: Routine FFR measurement is feasible in NSTEMI patients and has additive diagnostic, clinical and health economic utility, as compared to angiography-guided standard care.
Design: A prospective multi-center randomized controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% severity (threshold for FFR measurement). Patients will be randomized immediately after coronary angiography to the FFR-guided group or angiography-guided group (FFR measured, not disclosed). All patients will then undergo FFR measurement in all vessels with a coronary stenosis ≥30% severity. FFR will be measured in culprit and non-culprit lesions in all patients. FFR will be disclosed to guide treatment in the FFR guided-group but not disclosed in the 'angiography-guided' group. In the FFR-guided group, an FFR>0.80 will be an indication for medical therapy whereas an FFR≤0.80 will be an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG), as appropriate. The primary endpoint is the between-group difference in the proportion of patients allocated to medical management compared to revascularization. A key secondary composite outcome is the occurrence of cardiac death or hospitalization for myocardial infarction or heart failure. Other secondary outcomes include quality of life, hospitalization for unstable angina, coronary revascularization or stroke, and healthcare costs. Exploratory analyses will also assess the relationships between FFR and angiographic lesion characteristics (severity, culprit status). The minimum and average follow-up periods for the primary analysis are 6 and 18 months respectively. A secondary analysis with longer term follow-up (minimum 3 years) is planned. Screen failures who gave informed consent will be entered into a registry.
Importance: Our developmental clinical trial will address the feasibility of FFR measurement in NSTEMI and the influence of FFR disclosure on treatment decisions and health and economic outcomes.
Non-ST Elevation Myocardial Infarction.
Type 1 Myocardial Infarction.
Device: Fractional flow reserve
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
|Official Title:||A Developmental Clinical Study of Management Guided by Coronary Angiography Combined With Fractional Flow Reserve (FFR) Measurement Versus Management Guided by Coronary Angiography Alone(Standard Care) in Patients With Non-ST Elevation MI.|
- The between-group difference in the proportion of patients allocated to medical management compared to revascularization. [ Time Frame: Baseline: the treatment decision will be made by the clinical team in the cardiac catheter laboratory during the index procedure or shortly afterwards during the index hospitalization when a multidisciplinary heart team review is indicated. ] [ Designated as safety issue: No ]The between-group difference in the proportion of patients allocated to medical management compared to coronary revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG).
- The safety and feasibility of routine FFR measurement in patients with recent NSTEMI. [ Time Frame: Post randomization index procedure at baseline. ] [ Designated as safety issue: Yes ]
The safety of FFR measurement will be assessed by the occurrence of procedure-related adverse events including procedure-related myocardial infarction (Type 4a), coronary guidewire dissection, procedure duration and contrast nephropathy.
The feasibility of FFR measurement will be assessed by (1) the proportion of patients who have given informed consent and who are deemed eligible for a pressure wire study and (2) the proportion of patients in whom a pressure wire study is achieved based on the number of patients in whom a pressure wire study was attempted.
- The % rate of discordance between an FFR <= or >0.80 and coronary stenosis severity (stenosis > or <70% of reference vessel diameter (50% for left main) assessed visually). [ Time Frame: Baseline: Visual assessment of the angiogram before randomization, index procedure ] [ Designated as safety issue: No ]
The severity of coronary artery lesion(s) revealed by diagnostic coronary angiography will be visually assessed by the attending interventional cardiologist in the cardiac catheter laboratory in line with usual care. The assessment will be made and documented before randomization.
FFR will be measured during diagnostic coronary angiography and before PCI.
- Major adverse cardiac events are defined as cardiac death or hospitalization for myocardial infarction (MI) or heart failure. [ Time Frame: Post-randomization (any time including the index procedure through follow-up), expected average follow-up of 18 months (minimum follow-up 6 months). ] [ Designated as safety issue: Yes ]Major adverse cardiovascular events are defined as cardiovascular death or hospitalization for MI, heart failure, stroke or transient ischemic attack. Information on hospitalizations for other adverse events (i.e. unstable angina, renal failure, PCI, CABG) will be prospectively recorded. Receiver-operating-characteristics will be calculated for FFR in all patients and subsequent adverse events. The endpoints will be assessed during the study until the final randomized patient has completed a minimum of 6 months follow-up. The 3-year event rates will also be assessed.
- Health economics [ Time Frame: Post-randomization (including the index procedure through longer term mean follow-up of 18 months (minimum follow-up 6 months). ] [ Designated as safety issue: No ]Health-care costs (including revascularization procedures, stents, bed days etc) will be prospectively recorded for the index and any subsequent hospitalizations.
- Quality of life [ Time Frame: Baseline through longer term follow-up (average follow-up 18 months, minimum follow-up 6 months) ] [ Designated as safety issue: Yes ]Quality of life (EurQoL, EQ-5D-5L) assessed at 6 monthly intervals until the last randomized patient has completed a minimum of 6 months follow-up.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||May 2016|
|Estimated Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Fractional flow reserve
Fractional flow reserve - guided group:
The initial treatment decision and the coronary arteries for fractional flow reserve (FFR) measurement will be established and recorded before randomization. FFR will then be measured by the cardiologist immediately after randomization and the FFR result will used to guide treatment decisions based on a threshold of 0.80. An FFR ≤ 0.80 should result in a treatment decision for revascularization by PCI or CABG combined with optimal medical therapy and an FFR>0.80 should result in treatment with optimal medical therapy alone. Changes in treatment compared to the treatment plan prior to FFR disclosure will be recorded at the time.
Device: Fractional flow reserve
Guidewire-based coronary pressure measurement of myocardial FFR can identify obstructive coronary lesions in patients with stable coronary disease, and potentially, medically stabilized patients with recent MI. The FFR index is measured by a conventional coronary wire (0.014") with a pressure sensor on its distal tip during coronary hyperemia induced by intravenous or intracoronary adenosine. The potential diagnostic and prognostic benefit of guidewire-based coronary pressure measurement to inform the management and treatment of patients with recent acute NSTEMI will be assessed.
Placebo Comparator: Angiography-guided
FFR is measured by but not disclosed to the clinical team. Treatment decisions are therefore guided by angiography but not by FFR. The patient and the clinical team, including the cardiologists and nurses, will be blinded to FFR. The RadiAnalyzer Xpress (St Jude Medical) will be turned away from the clinical team who will not see the pressure wire data. FFR will not be displayed on any other monitor. Quality control checks, such as assessments of equalized pressure, will be done in the usual way, by the unblinded clinical research team. These steps will be followed for all FFR measurements. Adherence to the blinding protocol, including any non-protocol FFR disclosure at any time, will be prospectively recorded and blinding procedures will be monitored with site visits.
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|Golden Jubilee National Hospital|
|Clydebank, Dunbartonshire, United Kingdom, G81 4DY|
|Royal Blackburn Hospital|
|Blackburn, East Lancashire, United Kingdom, BB2 3HH|
|University Hospital Southampton NHS Foundation Trust|
|Southampton, Hampshire, United Kingdom, S016 6YD|
|East Kilbride, Lanarkshire, United Kingdom, G75 8RG|
|Newcastle-upon-Tyne, Tyne and Wear, United Kingdom, NE7 7DN|
|City Hospitals Sunderland NHS Foundation|
|Sunderland, Tyne and Wear, United Kingdom, SR4 7TP|
|Principal Investigator:||Colin Berry, MD PhD||University of Glasgow|
|Study Chair:||Robert Henderson, MD FRCP||Nottingham University Hospitals, Nottingham, UK|
|Study Director:||Ian Ford, PhD||Robertson Centre for Biostatistics, University of Glasgow|
|Study Director:||Andrew Briggs, PhD||Health Economics and Health Technology Assessment, University of Glasgow|