Clinical trial NCT03259815: An Evaluation of a Physiology-guided PCI Optimisation Strategy
Official title: How Often Can Optimal Post Percutaneous Coronary Intervention (PCI) Fractional Flow Reserve (FFR) Results be Achieved? - a Randomised Controlled Trial of FFR Targeted PCI (the Target FFR Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Coronary Stenosis
Keywords: FFR Targeted PCI
Post-PCI FFR
Physiology-guided PCI Optimisation
Lead sponsor: NHS National Waiting Times Centre Board
Sponsor class: OTHER
First posted: 2017-08-24
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised Controlled Trial
Primary purpose: TREATMENT

Brief summary: There has recently been renewed interest in the measurement of post percutaneous coronary intervention (PCI) Fractional Flow Reserve (FFR). Previous studies have suggested that post-PCI FFR values ≥0.90 are associated with better clinical outcomes for patients but the available data suggest that despite angiographically satisfactory results, this is actually achieved in less than 40% of cases.

The main mechanisms for sub-optimal post-PCI FFR measurements have been proposed to be suboptimal stent deployment, unmasking of a second lesion in the target vessel post PCI, residual diffuse disease in the untreated segments and pressure drift (a technical artefact of pressure wire technology).

Using post-PCI FFR to guide stent optimisation and/or further intervention in the target vessel has been shown to increase the frequency of achieving optimal post-PCI FFR results (and therefore presumably better clinical outcomes). However, there are additional costs involved in the routine use of post-PCI FFR and it is not clear just how often it is even possible to increase the initial post-PCI FFR to ≥0.90. This uncertainty means that it is currently difficult to either recommend the routine use of post-PCI FFR or justify its cost.

The investigators propose a prospective study to assess the feasibility of achieving post-PCI FFR ≥0.90 during standard PCI procedures in consecutive patients. The study would also attempt to elucidate the mechanisms for sub-optimal FFR results when they occur. The investigators anticipate using the data from this developmental study to support a subsequent funding application for a definitive phase 3 study of the impact of FFR targeted PCI on clinical outcomes.

Detailed description: Original hypothesis

A simple Physiology-guided Incremental Optimisation Strategy (PIOS) can increase the proportion of patients undergoing PCI in whom a post-PCI FFR ≥0.90 can be achieved from 40% to 60%.

Experimental details and design of proposed investigation

Overall aim:

A randomised controlled trial of a physiology-guided optimisation strategy to determine the feasibility of increasing the proportion of post-PCI FFR measurements ≥0.90 in a consecutive series of patients undergoing standard PCI procedures.

Study Population:

260 consecutive patients with stable angina referred for invasive management to the cardiac catheterisation lab who have been selected to undergo PCI based on either angiographic appearances or prior FFR assessment. Patients will be caffeine free for \>12 hours pre-procedure.

Methods/Design:

Informed consent will be obtained prior to cardiac catheterisation in all potential subjects conforming to the inclusion and exclusion criteria.

Patients will then be randomised to one of two groups (described below) and PCI will be performed, using a pressure guidewire, according to standard practice at the Golden Jubilee National Hospital (including lesion pre-dilation and post-dilation of the stented segment).

Group 1 (PIOS Group):

Operator-blinded coronary physiology measurements will be recorded pre and post PCI.

If the post-PCI FFR is ≥0.90, no further intervention will be performed and the procedure is considered complete.

If post-PCI FFR is \<0.90, the result will be disclosed to the operator and a hyperaemic pressure wire pullback during a standard peripheral intravenous adenosine infusion (140mcg/kg/min) will be performed. Depending on the result the operator would then have the following options:

A. If there is a step-up of ≥0.05 across the stented segment(s) further post-dilatation with a 0.25 - 0.50mm larger non-compliant balloon to at least 18 atmospheres should be performed followed by repeat FFR. Alternatively, the operator may choose to employ intracoronary imaging (IVUS or OCT) to guide post-dilation/optimisation of the stented segment.

B. If there is a step-up of ≥0.05 across a relatively focal (\<20mm) unstented segment which is technically suitable for further stenting then a further stent should be implanted followed by repeat FFR.

C. If the FFR remains \<0.90 after steps A +/- B, a further FFR pullback will be performed. If the criteria for Step B are again met, one additional stent may be deployed and a final FFR pullback performed. Following this, the FFR result will be accepted.

D. If the residual pressure gradient is interpreted to reflect diffuse atherosclerosis with no focal step-ups, the result is accepted.

E. At the end of the procedure the pressure wire sensor will be withdrawn to the tip of the guiding catheter and compared with the aortic pressure. A pressure drift of ≤0.03 will be accepted and the final FFR result adjusted accordingly.

F. If there is a drift of ≥0.04, the wire should be re-equalised and the final FFR measurement be repeated.

G. The patients will have their demographics and procedure details recorded. All patients will be asked to complete follow-up questionnaires at 3 months.

Group 2 (Control Group):

Pre and post-PCI coronary physiology measurements will be recorded but not disclosed to the operator. The angiographically defined result will be accepted. The patients will have their demographics and procedure details recorded. All patients will be asked to complete follow-up questionnaires at 3 months.

Expected value of results

1. Confirmation that the proposed PIOS protocol significantly increases the proportion of patients obtaining a physiologically optimal post-PCI result will demonstrate the feasibility of this strategy and should lead to an increase in post-PCI pressure wire usage to achieve physiologically optimal results for patients.

   The investigators hypothesise that the PIOS intervention can increase the proportion of patients achieving this target from 40% to 60% and believe that an increment of at least this magnitude would be necessary to make a future larger study with both patient-oriented clinical (target vessel failure) and health care system (resource utilisation) outcomes acceptable to the interventional cardiology community and potential funders.
2. The secondary outcome measures, albeit underpowered for clinical outcomes in this study, will hopefully still give a signal that achieving a target post-PCI FFR ≥0.90 does yield objective benefits for patients. This could then form the basis for a larger phase 3 trial to confirm improved clinical outcomes and cost- effectiveness of FFR-targeted PCI

Eligibility criteria: Inclusion Criteria:

* Patients \>18 years of age with coronary artery disease (including stable angina and stabilised non-ST-elevation myocardial infarction (NSTEMI)) who are able to provide informed consent.

Exclusion Criteria:

* PCI in a coronary artery bypass graft
* PCI to an in-stent restenosis (ISR) lesion
* PCI to a target artery providing Rentrop grade 2 or 3 collateral blood supply to another vessel
* Inability to receive adenosine (for example, severe reactive airway disease, marked hypotension, or advanced atrioventricular block without pacemaker).
* Recent (within 1 week prior to cardiac catheterization) ST-segment elevation myocardial infarction (STEMI) in any arterial distribution (not specifically target lesion).
* Severe cardiomyopathy (ejection fraction \<30%).
* Renal insufficiency such that an additional 20 to 30 mL of contrast would, in the opinion of the operator, pose unwarranted risk to the patient.

Primary outcomes:
measure: The proportion of patients with a final post-PCI FFR result ≥0.90
timeFrame: 1 day
Secondary outcomes:
measure: The proportion of patients with final post-PCI FFR ≤0.80
timeFrame: 1 day
measure: Change from baseline in self-reported health outcomes at 3 months using a disease-specific quality of life measurement tool.
timeFrame: 3 months
measure: Change from baseline in self-reported health outcomes at 3 months using a generic quality of life measurement tool.
timeFrame: 3 months
measure: The rate of target vessel failure (TVF) and its component features at 3 months.
timeFrame: 3 months
measure: The rate of target vessel failure (TVF) and its component features at 1 year.
timeFrame: 1 year
measure: Change from baseline in the FFR following PCI
timeFrame: 1 day
measure: The proportion of patients with final post-PCI dPR ≥0.90
timeFrame: 1 day
measure: Change from baseline in the Diastolic Pressure Ratio (dPR) following PCI
timeFrame: 1 day
measure: The proportion of patients with final post-PCI RFR ≥0.90
timeFrame: 1 day
measure: Change from baseline in the Resting Full-Cycle Ratio (RFR) following PCI
timeFrame: 1 day
measure: Change in TTrest following PCI
timeFrame: 1 day
measure: Change in TThyp following PCI
timeFrame: 1 day
measure: The proportion of patients with final post-PCI CFR value ≥2.0
timeFrame: 1 day
measure: Change from baseline in the Coronary Flow Reserve (CFR) following PCI
timeFrame: 1 day
measure: The proportion of patients with final post-PCI IMR >25
timeFrame: 1 day
measure: Change from baseline in the Index of Microcirculatory Resistance (IMR) following PCI
timeFrame: 1 day
measure: The proportion of patients with final post-PCI IMRc >25
timeFrame: 1 day
measure: Procedure Duration
timeFrame: 1 day
measure: The cost of additional equipment employed in the experimental arm
timeFrame: 1 day
measure: Fluoroscopy Dose
timeFrame: 1 day
measure: Contrast Material Dose
timeFrame: 1 day
measure: Incidence of procedural complications such as coronary artery dissection or perforation.
timeFrame: 1 day
Other outcomes:
measure: 'As Treated' analysis of the proportion of patients with a final post-PCI FFR result ≥0.90
timeFrame: 1 day
measure: 'As Treated' analysis of the proportion of patients with final post-PCI FFR ≤0.80
timeFrame: 1 day
measure: 'As Treated' analysis of the change from baseline in self-reported health outcomes at 3 months as assessed by the Seattle Angina Questionnaire (SAQ)
timeFrame: 3 months
measure: 'As Treated' analysis of the change from baseline in self-reported health outcomes at 3 months as assessed by the EQ-5D questionnaire.
timeFrame: 3 months
measure: 'As Treated' analysis of the rate of target vessel failure (TVF) and its component features at 3 months.
timeFrame: 3 months
measure: 'As Treated' analysis of the rate of target vessel failure (TVF) and its component features at 1 year.
timeFrame: 1 year
measure: 'As Treated' analysis of the change from baseline in the FFR following PCI
timeFrame: 1 day
measure: 'As Treated' analysis of the proportion of patients with final post-PCI dPR ≥0.90
timeFrame: 1 day
measure: 'As Treated' analysis of the change from baseline in the dPR following PCI
timeFrame: 1 day
measure: 'As Treated' analysis of the proportion of patients with final post-PCI RFR ≥0.90
timeFrame: 1 day
measure: 'As Treated' analysis of the change from baseline in the RFR following PCI
timeFrame: 1 day
measure: 'As Treated' analysis of the change in TTrest following PCI
timeFrame: 1 day
measure: 'As Treated' analysis of the change in TThyp following PCI
timeFrame: 1 day
measure: 'As Treated' analysis of the proportion of patients with final post-PCI CFR value ≥2.0
timeFrame: 1 day
measure: 'As Treated' analysis of the change from baseline in the CFR following PCI
timeFrame: 1 day
measure: 'As Treated' analysis of the proportion of patients with final post-PCI IMR >25
timeFrame: 1 day
measure: 'As Treated' analysis of the change from baseline in the IMR following PCI
timeFrame: 1 day
measure: 'As Treated' analysis of the proportion of patients with final post-PCI IMRc >25
timeFrame: 1 day
Locations:
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
Study officials:
affiliation: NHS National Waiting Times Centre Board (NHS Golden Jubilee)
name: Keith G Oldroyd, MB, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Collison D, McClure JD, Berry C, Oldroyd KG. A randomized controlled trial of a physiology-guided percutaneous coronary intervention optimization strategy: Rationale and design of the TARGET FFR study. Clin Cardiol. 2020 May;43(5):414-422. doi: 10.1002/clc.23342. Epub 2020 Feb 10.
citation: Collison D, Didagelos M, Aetesam-Ur-Rahman M, Copt S, McDade R, McCartney P, Ford TJ, McClure J, Lindsay M, Shaukat A, Rocchiccioli P, Brogan R, Watkins S, McEntegart M, Good R, Robertson K, O'Boyle P, Davie A, Khan A, Hood S, Eteiba H, Berry C, Oldroyd KG. Post-stenting fractional flow reserve vs coronary angiography for optimization of percutaneous coronary intervention (TARGET-FFR). Eur Heart J. 2021 Dec 1;42(45):4656-4668. doi: 10.1093/eurheartj/ehab449.