Clinical trial NCT02425969: A Trial in Stable Intermediate Coronary Lesions and Grey-zone FFR Values
Official title: A Randomised Controlled Trial in Stable Intermediate Coronary Lesions and Grey-zone FFR Values With Evaluation of the Diagnostic Utility of Invasive Coronary Physiological Indices and Quantitative Perfusion MRI. The GzFFR Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Grey-zone Fractional Flow Reserve
Intermediate Coronary Lesions
Stable Angina
Coronary Physiology
Lead sponsor: Golden Jubilee National Hospital
Sponsor class: OTHER_GOV
Collaborators: name: British Heart Foundation
name: University of Glasgow
First posted: 2015-04-24
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this randomised controlled trial of patients with stable angina and documented intermediate coronary disease with indeterminate or "grey-zone" Fractional Flow Reserve (FFR) we will randomise patients to either optimal medical therapy alone versus optimal medical therapy with PCI and they will be followed up for the primary endpoint of anginal control as measured by the Seattle Angina Questionnaire at 3 months.

Detailed description: Pressure derived fractional flow reserve (FFR) is recognised as being the gold standard method of assessing the physiological significance of angiographically intermediate lesions. A grey-zone exists between the originally validated cut-off for ischemia of \<0.75 and the conventionally adopted cut- off of ≤0.80. Pilot data from our centre has suggested that only 1 in 3 coronary arteries with grey-zone FFR values demonstrate myocardial perfusion defects on stress cardiac MRI and others have suggested that the clinical outcomes in patients with grey-zone FFR are favorable with medical therapy alone. As such, stenting all lesions with grey-zone FFR (as currently recommended) may represent over-treatment and could attenuate the overall benefit of an FFR strategy. In addition to this there are flow derived resistance indices of stenosis severity that have superior diagnostic accuracy and may be helpful in correctly classifying patients with grey-zone FFR. In this study we will a comprehensive analysis of lesions with grey-zone FFR values (0.75-0.82 inclusive) using invasive hyperemic pressure, flow and resistance derived indices of severity with quantitative and qualitative 3T perfusion MRI to enable identification of the best invasive predictors of true perfusion defects on 3T cardiac MRI. Patients will be randomised to optimal medical therapy alone versus optimal medical therapy with PCI and followed up for the primary endpoint of anginal control as measured by the Seattle Angina Questionnaire at 3 months.

Eligibility criteria: Inclusion Criteria:

1. Patients \>18 years
2. 30-80% Diameter Stenosis on QCA
3. Stable angina
4. Non ST-elevation myocardial infarction (NSTEMI) with stable symptoms
5. Able to provide informed consent

Exclusion Criteria:

1. STEMI within 5 days
2. Tortuous vessels which would render pressure wire studies difficult or impossible
3. Heavily calcified vessels which would render pressure wire studies difficult or impossible
4. Unstable symptoms requiring definitive interventional management
5. Severe claustrophobia
6. Age \>90 years
7. Life expectancy \<1 year
8. Estimated Glomerular Filtration Rate \<30 mls/min/1.73m2
9. Inability to undergo MRI scanning due to metallic implant or incompatible permanent pacemaker
10. Severe asthma or inability to safely receive an adenosine infusion
11. Left mainstem disease ≤50% or if considered clinically significant by the operating cardiologist either on angiography or intravascular ultrasound.

Primary outcomes:
measure: Angina status as per Seattle Angina Questionnaire
timeFrame: 3 months
Secondary outcomes:
measure: MACE
timeFrame: 3 and 12 months
measure: Myocardial infarction
timeFrame: 3 and 12 months
measure: Urgent Revascularisation
timeFrame: 3 and 12 months
measure: Total number of anti-anginal medications
timeFrame: 3 and 12 months
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
state: Dunbartonshire
Study officials:
affiliation: National Health Service
name: Keith G Oldroyd, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hennigan B, Berry C, Collison D, Corcoran D, Eteiba H, Good R, McEntegart M, Watkins S, McClure JD, Mangion K, Ford TJ, Petrie MC, Hood S, Rocchiccioli P, Shaukat A, Lindsay M, Oldroyd KG. Percutaneous coronary intervention versus medical therapy in patients with angina and grey-zone fractional flow reserve values: a randomised clinical trial. Heart. 2020 May;106(10):758-764. doi: 10.1136/heartjnl-2019-316075. Epub 2020 Feb 29.