In the Management of Coronary Artery Disease, Does Routine Pressure Wire Assessment at the Time of Coronary Angiography Affect Management Strategy, Hospital Costs and Outcomes?

Study Overview
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Brief Summary
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A randomised controlled trial to compare two strategies for the investigation of coronary artery disease at the time of angiography. Patients will be randomised to conventional angiography or additional, routine pressure wire assessment - measuring fractional flow reserve (FFR) - in all main vessels judged as being of sufficient vessel calibre to allow percutaneous coronary intervention (PCI) (experimental arm).

Detailed Description
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The study will recruit patients undergoing angiography for the investigation of stable angina or for the assessment of a recent, but stabilised, non-ST elevation acute coronary syndrome event. Eligible patients who provide written informed consent will be randomised to conventional angiography or additional, routine pressure wire assessment - measuring fractional flow reserve (FFR) - in all main vessels judged as being of sufficient vessel calibre to allow percutaneous coronary intervention (PCI) (experimental arm). The study pragmatic design allows investigators to conduct all diagnostic and therapeutic management in accordance with prevailing best practice patterns. Study outcome measures will examine resource utilisation, patient reported quality of life and clinical events at 1 year.

Official Title
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A Randomised Controlled Trial to Compare Routine Pressure Wire Assessment With Conventional Angiography in the Management of Patients With Coronary Artery Disease.

Conditions
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Chest Pain, Stable Angina, Acute Coronary Syndrome, Non ST Segment Elevation Acute Coronary Syndrome

Intervention / Treatment
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* Device: Routine Measurement of FFR


Participation Criteria
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Eligibility Criteria
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· Inclusion criteria o Outline Initial Inclusion Criteria (before entry to cath lab): Patient scheduled for coronary angiography for the: Elective investigation of known or suspected coronary artery disease OR Urgent investigation of a recent but stabilised, non-ST elevation acute coronary syndrome event o Outline Angiographic Inclusion Criterion (after angiography): Presence of significant coronary disease defined as: Any stenosis >30% reduction in luminal diameter, by visual estimate, in at least one vessel (main or branch) of sufficient calibre to permit the potential performance of PCI - approximately 2.25 mm diameter. Key Exclusion Criteria Screening phase exclusion criteria: ≤ 18 years of age Previous enrolment in this trial Currently enrolled into another study unless co-enrolment approved by Chief Investigator (CI) and the clinical trials unit (CTU) Inability to provide informed consent Residence outside the United Kingdom (UK) or other issues limiting the ability to secure clinical follow-up data to one year Non-cardiac pathology that may limit survival in the next year Clear contraindication to potential future management with CABG or PCI (patients should be a potential candidate for medical therapy or revascularisation with either PCI or surgery) Heart valve disease of sufficient import to consider valve replacement or other intervention as part of an index management strategy Hypertrophic cardiomyopathy Previous coronary artery surgery of any type Known chronic renal impairment with a current estimated glomerular filtration rate (eGFR) of < 45 Anaemia with a current measured haemoglobin of < 100 Angiography performed in the context of an ST elevation myocardial infarction event Any patient who at the time of planned angiography manifests haemodynamic instability, or recurrent sustained ventricular arrhythmia, or Mobitz type II or complete heart block Any patient who at the time of planned angiography manifests unstable chest pain symptoms at rest or has required the continuing use of intravenous nitrates or regular opioid analgesia to control symptoms Continuing use of intravenous glycoprotein 2b/3a (GP2b3a) agents before entry to the catheterisation laboratory Known intolerance, hypersensitivity or contraindication to adenosine - including significant reversible airways disease Additional investigations planned (or deemed likely to be required) for the assessment of myocardial ischaemia or viability. Examples of proposed tests that would constitute an exclusion criterion would include, but are not limited to, exercise tolerance testing, stress echocardiography, cardiac MRI viability or perfusion scanning or nuclear myocardial perfusion scanning. Active bleeding at the time of planned index angiography Pregnant women Angiographic phase exclusion criteria: Single vessel occlusive coronary disease (TIMI flow <3) as sole disease Patient not suitable for the immediate performance of a pressure wire assessment of all major vessels for any reason, for example: Patient discomfort Change in the clinical condition or complication of angiography requiring termination of the procedure or immediate intervention Significant use of radiographic contrast or X-Ray exposure during the initial angiography Inadequate angiographic images or failure to intubate any of the coronary vessels Aorto-ostial disease that would preclude accurate assessment of FFR Insufficient laboratory time Uncertain availability of key clinical and trial staff PW use in coronaries declared unsafe (e.g. tight or long disease) PW use in coronaries declared unsuitable (e.g. distal disease or complete cross-filling)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional angiography<br>Routine angiography will be performed according to local best practice | |
| Experimental: Routine Measurement of FFR<br>Additional investigation with the measurement of FFR in all major vessels | Device: Routine Measurement of FFR<br>* FFR measurement will be performed in all major vessels with normal (TIMI 3) flow. Occluded vessels and vessels with TIMI flow <3 will not be examined but will be 'awarded' an FFR value of 0.5<br>* Other names: Pressure wire assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Economic Outcome Measure | Resource utilisation as determined by hospital care costs at one year; All hospital admissions will be tracked using national hospital episode statistics; the cost of each episode will be derived from a cost model using standard UK tariffs. This analysis will compare the mean (or median) of the total hospital costs recorded for each patient over the 12 month follow-up period. | One year | 
| Primary Quality of Life Outcome Measure | Patient reported quality of life at one year using the EQ-5D health questionnaire. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Management strategy information | · Proportion of vessels deemed to demonstrate flow-limiting disease and targeted for revascularisation in the declared initial management strategy. | Reported once: Single declaration at index procedure after randomisation | 
| Management strategy information | · Proportion of patients scheduled for management with medical therapy, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in the declared initial management strategy. | Reported once: Single declaration at index procedure after randomisation | 
| Angina symptoms | • Angina symptoms as reported by the research team after the 12 month contact, described by Canadian Cardiovascular Society Grade. | One year | 
| Angina symptoms | • Angina symptoms as reported by the patient with private completion of a screening form at 12 months, described by Canadian Cardiovascular Society Grade. | One year | 
| All-cause mortality |  | One year | 
| Number of hospitalisation events |  | One year | 
| Total hospital days |  | One year | 
| Hospitalisation events | Hospitalisation events coded as cerebro-vascular accident (CVA). | One year | 
| Hospitalisation events | Hospitalisation events coded as myocardial infarction. | One year | 
| Hospitalisation events | Hospitalisation events coded as Coronary revascularisation. This analysis will involve a pre-specified subgroup analysis of: Planned revascularisation - if declared as the index strategy. All additional revascularisation events. | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fractional flow reserve (FFR), Pressure wire (PW), Coronary angiography