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NCT Number: NCT03259815

An Evaluation of a Physiology-guided PCI Optimisation Strategy

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.

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Key information

Conditions

Coronary Artery Disease Arterial Occlusive Diseases Arteriosclerosis Cardiovascular Diseases Coronary Disease Coronary Stenosis Heart Diseases Myocardial Ischemia Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Golden Jubilee National Hospital

Glasgow, G81 4DY, United Kingdom

About this study

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

  • 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.

  • 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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

P.I.O.S.

Procedure

Physiologically-Guided Incremental Optimisation Strategy

Pre and post-PCI coronary physiology measurements

Diagnostic Test

Pre and post-PCI coronary physiology measurements will be performed but not disclosed to the operator

Primary outcomes

  1. The proportion of patients with a final post-PCI FFR result ≥0.90

    Time frame: 1 day

    The proportion of patients with a final post-PCI FFR result ≥0.90 will be compared between the randomised groups

Secondary outcomes

  1. The proportion of patients with final post-PCI FFR ≤0.80

    Time frame: 1 day

    The proportion of patients with a final post-PCI FFR result ≤0.80 will be compared between the randomised groups

  2. Change from baseline in self-reported health outcomes at 3 months using a disease-specific quality of life measurement tool.

    Time frame: 3 months

    Patients will complete the Seattle Angina Questionnaire (SAQ) at baseline pre-procedure and again at 3 months post PCI

  3. Change from baseline in self-reported health outcomes at 3 months using a generic quality of life measurement tool.

    Time frame: 3 months

    Patients will complete the EQ-5D questionnaire at baseline pre-procedure and again at 3 months post PCI

  4. The rate of target vessel failure (TVF) and its component features at 3 months.

    Time frame: 3 months

    Component features of TVF include cardiac death, myocardial infarction, stent thrombosis, unplanned rehospitalisation with target vessel revascularisation.

  5. The rate of target vessel failure (TVF) and its component features at 1 year.

    Time frame: 1 year

    Component features of TVF include cardiac death, myocardial infarction, stent thrombosis, unplanned rehospitalisation with target vessel revascularisation.

  6. Change from baseline in the FFR following PCI

    Time frame: 1 day

    The difference between measurements of Fractional Flow Reserve taken in the target vessel pre- and post-PCI

  7. The proportion of patients with final post-PCI dPR ≥0.90

    Time frame: 1 day

    The proportion of patients with a final post-PCI Diastolic Pressure Ratio (dPR) value ≥0.90

  8. Change from baseline in the Diastolic Pressure Ratio (dPR) following PCI

    Time frame: 1 day

    The difference between measurements of the Diastolic Pressure Ratio taken in the target vessel pre and post PCI

  9. The proportion of patients with final post-PCI RFR ≥0.90

    Time frame: 1 day

    The proportion of patients with a final post-PCI Resting Full-cycle Ratio (RFR) value ≥0.90

  10. Change from baseline in the Resting Full-Cycle Ratio (RFR) following PCI

    Time frame: 1 day

    The difference between measurements of the Resting Full-Cycle Ratio (the lowest Pd/Pa ratio during the whole cardiac cycle at rest) taken in the target vessel pre and post PCI

  11. Change in TTrest following PCI

    Time frame: 1 day

    Change of the thermodilution-derived resting transit time (TTrest) from pre-PCI to final post-PCI value

  12. Change in TThyp following PCI

    Time frame: 1 day

    Change of the thermodilution-derived hyperaemic transit time (TThyp) from pre-PCI to final post-PCI value

  13. The proportion of patients with final post-PCI CFR value ≥2.0

    Time frame: 1 day

    The proportion of patients with a final post-PCI Coronary Flow Reserve (CFR) result ≥2.0

  14. Change from baseline in the Coronary Flow Reserve (CFR) following PCI

    Time frame: 1 day

    The difference between measurements of Coronary Flow Reserve taken in the target vessel pre and post PCI

  15. The proportion of patients with final post-PCI IMR >25

    Time frame: 1 day

    The proportion of patients with a final post-PCI Index of Microcirculatory Resistance (IMR) value >25

  16. Change from baseline in the Index of Microcirculatory Resistance (IMR) following PCI

    Time frame: 1 day

    The difference between measurements of IMR taken in the target vessel pre and post PCI

  17. The proportion of patients with final post-PCI IMRc >25

    Time frame: 1 day

    The proportion of patients with a final post-PCI corrected Index of Microcirculatory Resistance (IMRc) value >25

  18. Procedure Duration

    Time frame: 1 day

    The time required to perform the PIOS intervention procedures will be compared with those in the control group.

  19. The cost of additional equipment employed in the experimental arm

    Time frame: 1 day

    The cost of additional equipment employed in the PIOS intervention (i.e. balloons/stents/intra-coronary imaging).

  20. Fluoroscopy Dose

    Time frame: 1 day

    The radiation doses for the PIOS intervention procedures will be compared with those in the control group.

  21. Contrast Material Dose

    Time frame: 1 day

    The contrast material doses for the PIOS intervention procedures will be compared with those in the control group.

  22. Incidence of procedural complications such as coronary artery dissection or perforation.

    Time frame: 1 day

    The incidence of procedural complications such as coronary artery dissection or perforation will be recorded and compared between the two study arms

Other outcomes

  1. 'As Treated' analysis of the proportion of patients with a final post-PCI FFR result ≥0.90

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  2. 'As Treated' analysis of the proportion of patients with final post-PCI FFR ≤0.80

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  3. 'As Treated' analysis of the change from baseline in self-reported health outcomes at 3 months as assessed by the Seattle Angina Questionnaire (SAQ)

    Time frame: 3 months

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  4. 'As Treated' analysis of the change from baseline in self-reported health outcomes at 3 months as assessed by the EQ-5D questionnaire.

    Time frame: 3 months

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  5. 'As Treated' analysis of the rate of target vessel failure (TVF) and its component features at 3 months.

    Time frame: 3 months

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  6. 'As Treated' analysis of the rate of target vessel failure (TVF) and its component features at 1 year.

    Time frame: 1 year

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  7. 'As Treated' analysis of the change from baseline in the FFR following PCI

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  8. 'As Treated' analysis of the proportion of patients with final post-PCI dPR ≥0.90

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  9. 'As Treated' analysis of the change from baseline in the dPR following PCI

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  10. 'As Treated' analysis of the proportion of patients with final post-PCI RFR ≥0.90

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  11. 'As Treated' analysis of the change from baseline in the RFR following PCI

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  12. 'As Treated' analysis of the change in TTrest following PCI

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  13. 'As Treated' analysis of the change in TThyp following PCI

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  14. 'As Treated' analysis of the proportion of patients with final post-PCI CFR value ≥2.0

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  15. 'As Treated' analysis of the change from baseline in the CFR following PCI

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  16. 'As Treated' analysis of the proportion of patients with final post-PCI IMR >25

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  17. 'As Treated' analysis of the change from baseline in the IMR following PCI

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

  18. 'As Treated' analysis of the proportion of patients with final post-PCI IMRc >25

    Time frame: 1 day

    The primary efficacy analyses of the study intervention will be carried according to the 'intention to treat' principle (i.e. results will be compared between randomised groups according to the pre-specified outcome measures).

    An 'As Treated' analysis will also be performed as an additional outcome measure. This will compare patients who actually received the PIOS intervention with those who did not.

Sponsors and collaborators

Lead sponsor

NHS National Waiting Times Centre Board

Other

Registry information

Official study 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)

Acronym: Target-FFR

Important dates

Study start
2018
Primary completion
2019
Study completion
2020
First posted
Aug 24, 2017
Registry last updated
Mar 31, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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