RFR and FFR for the the Prediction of Post-PCI Results (PICIO)

Pullback wIth Resting Full-Cycle Flow ratIO or Fractional Flow Reserve for the Prediction of Post-PCI Hemodynamic Outcomes. A Study in Patients With Diffuse Coronary Artery Disease

The aim of this study is to record hemodynamic pullback information using continuous resting full-cycle flow ratio (RFR) and fractional flow reserve (FFR) in patients with diffuse coronary artery disease. The capacity of the two indexes to predict the hemodynamic outcome after stenting will be compared.

Goals of the study are:

• To study the accuracy of RFR/FFR gradients in predicting the change in whole-vessel RFR/FFR after PCI.
• To identify a threshold in the RFR/FFR gradient that is predictive of pathological RFR/FFR also after the PCI of the first lesion.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Diagnostic test: RFR; Diagnostic test: FFR

Detailed Description

The study of the hemodynamic relevance of coronary stenoses is a well-validated method to identify coronary lesions to be treated. A number of studies show that FFR-guided PCI is superior to angiography guided PCI2-4. The achievement of maximal hyperemia is a prerequisite for FFR measurements. Hyperemia is usually achieved with the intravenous or intracoronary infusion of adenosine, which requires time and is potentially associated with discomfort for the patient. To avoid this, resting indexes have been developed. The instantaneous flow reserve (iFr) was the first of these indexes, and two large studies have shown that this parameter is non-inferior to FFR in terms of patient prognosis5. More recently, a number of other parameters have been developed, among which the RFR (resting flow ratio), which can be measured with the same intracoronary wire as the FFR and therefore requires no additional procedures. Studies show that these methods are equivalent6. The advantage of these resting indexes (which are all included in the most recent AHA/ACC guidelines7, 8), is that they do not require hyperemia. This might represent a particular advantage in the setting of tandem stenoses or diffuse disease. Since hyperemic flow in a vessel is limited by each one of the stenoses present in that vessel, each individual stenosis limits the capacity of FFR to assess the hemodynamic relevance of the other ones. In other words, invasive measurements of coronary hemodynamics using FFR in the setting of diffuse or tandem lesions are complicated by the fact that maximal hyperemia cannot be achieved, which limits the capacity of FFR to assess the hemodynamic relevance of individual focal stenoses. In this setting, the usual binary system (FFR < or > 0.80) cannot be easily applied.

This limitation is independent of the sequence of the stenoses: proximal lesions limit the reliability of FFR measurements in distal stenoses and vice versa (as long as no significant side branches are present between the two lesions). Since hyperemic flow declines significantly as soon as a 50% reduction in lumen diameter is present, even apparently non-relevant lesions may compromise any assessment based on hyperemia. This phenomenon, called hemodynamic interdependence of stenoses under conditions of hyperemia represents a significant limitation that applies to FFR but not to hyperemia-free indexes.

In order to address this issue in routine practice, FFR is measured first, then a pullback is performed and the lesion/segment where the pullback identifies the highest gradient is treated first. The removal of this stenosis increases maximal achievable hyperemic flow, thus increasing the significance of the remaining lesions. FFR is then measured again to test the hemodynamic significance of the other stenoses at a higher level of hyperemia. The capacity of FFR to predict whether removal of the first stenosis will be associated with the normalization of FFR is very limited, which requires that FFR be measured multiple times, prolonging the procedure and increasing the discomfort for the patient.

When studying coronary stenoses, the advantage of resting hemodynamic indexes is that non-critical stenoses (ie below 90%) do not modify resting blood flow. Because resting flow is more constant, and the effect of PCI is minimal, resting pressure changes measured across sequential lesions are likely to be more predictable.The hypothesis of the study is that, as compared to FFR, RFR will provide a better estimate of post-PCI hemodynamic outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tommaso Gori; Phone Number: +491721052846; Email: tomgori@hotmail.com

Study Locations

• Germany
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Recruiting
      • Center of Cardiology, Cardiology I, university hospital Mainz
      • Contact: Tommaso Gori, Prof Dr, PhD; Phone Number: +49 (0) 6131 17 2729; Email: tommaso.gori@unimedizin-mainz.de
      • Principal Investigator: Tommaso Gori, Prof Dr, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must meet ALL of the inclusion criteria:

  • Clinical indication for elective percutaneous coronary intervention of a stenosis >40% and <90% with clinical indication to percutaneous intervention (PCI) requiring functional assessment. Note: the decision to perform functional assessment will have to be taken before, and independently of, the inclusion and randomization in the study.
  • Documented heart team (when applicable, as per guidelines) decision for revascularization via PCI
  • Patient ≥18 years old

Exclusion Criteria:

• Patients will be excluded if ANY of the exclusion criteria is met:

  • Cardiogenic shock
  • Any contraindication to PCI according to guidelines
  • Presence of a coronary artery bypass grafting (CABG) in the territory under study
  • Culprit vessels in patients with ST-segment elevation myocardial infarction (STEMI)
  • TIMI (Thrombolysis in Myocardial Infarction) flow grade < 3
  • Lesion severity > 90% by visual assessment
  • Presence of thrombus
  • Participation in another randomized interventional study
  • Patient unable to give informed consent
  • Women of child-bearing potential or lactating

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RFR: resting full-cycle ratio; RFR will be used to drive PCI	Diagnostic test: RFR; Measurement of resting flow ratio
Active Comparator: FFR: fractional flow reserve; FFR will be used to drive PCI	Diagnostic test: FFR; Measurement of fractional flow reserve

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute difference between RFR observed and expected as compared to FFR observed versus expected.	Comparison of |RFRexp-RFRobs| vs. |FFRexp-FFRobs| (i.e., absolute differences between expected and observed final hemodynamic result) RFRexp and FFRexp are defined as (RFRbas plus RFRGrad) and (FFRbas plus FFRGrad)	1 day

Collaborators and Investigators

• Sponsor: Johannes Gutenberg University Mainz

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2020
• Primary Completion (Estimated): June 10, 2025
• Study Completion (Estimated): June 10, 2025

Study Registration Dates

• First Submitted: June 1, 2020
• First Submitted That Met QC Criteria: June 1, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Angina; stent; coronary stenosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: 2020-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No