Resting Full-cycle Ratio (RFR)-Guided Revascularization

Prospective Evaluation of Long-term Clinical Outcomes After Resting Full-cycle Ratio (RFR)-Guided Percutaneous Coronary Revascularization; A Multi-center, International, Single Arm Interventional, Comparing Registry (COMFORT Study)

The purpose of this study is to compare the clinical outcomes of a 2-year follow-up to determine whether RFR-guided coronary intervention is non-inferior to FFR-guided coronary intervention in patients with intermediate coronary stenosis.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Diagnostic test: Resting full-cycle ratio (RFR)-guided revascularization; Diagnostic test: Fractional flow ratio (FFR)-guided revascularization

Detailed Description

Myocardial ischemia is a key determinant of clinical prognosis in patients with coronary artery disease. In this regard, functional assessment of intermediate coronary stenoses with transtenotic pressure ratios provides a more accurate measure of stenosis-derived myocardial ischemia in comparison to conventional coronary angiography (3-5). One of the major clinical benefit of fractional flow reserve (FFR) is that, by acting as a gatekeeper, non-ischemia-causing lesions suitable for optimal medical treatment can be accurately identified, avoiding unnecessary coronary stenting. However, despite being support with the highest level of recommendation by the current guidelines for guiding clinical-decision making, adoption of FFR in the real world practice is still very low, mainly due to the need of hyperemic agents like adenosine that frequently cause patient discomfort, and time consumption. To overcome such limitations of pressure-wire derived index from the need of adenosine, other alternatives have been looking for over the last years. Instantaneous wave-free ratio (iFR), a resting trans-stenotic pressure index obtained as the ratio of distal coronary pressure to aortic pressure during the diastolic wave-free period, demonstrated a good diagnostic accuracy to define functional significance of coronary lesions without need of adenosine, using FFR as reference. Recently, two large, randomized trials demonstrated that iFR-guided coronary revascularization is clinically non-inferior to FFR-guided revascularization with respect to one-year risk of major adverse cardiac events. Accordingly, like FFR, iFR is now receiving the highest level of recommendations to guide clinical decision making in patients with stable intermediate coronary stenosis. A new adenosine-free index, the resting full-cycle ratio (RFR), has recently emerged. RFR is defined as the lowest ratio of intracoronary distal pressure to aortic pressure under resting condition, irrespective of systole or diastole, and has demonstrated equivalent diagnostic performance to iFR. RFR has an advantage over iFR, because it is not limited by sensitive land marking of components of the pressure waveform unlike iFR.

This novel physiologic index without the need of adenosine has the potential to increase the worldwide adoption of coronary physiology in guiding coronary revascularization in daily clinical practice. However, there is a paucity of important data regarding clinical outcomes of RFR-guided revascularization strategy. We hypothesize long-term clinical outcome of RFR-guided revascularization is non-inferior to that of FFR-guided revascularization, and it reduce the rate of PCI than FFR-guided revascularization. Therefore, we sought to investigate the long-term effectiveness and safety of RFR-based decision making in patients with one or more intermediate coronary stenosis, and to assess whether it is non-inferior to FFR-guided revascularization.

• Study Type: Observational
• Enrollment (Estimated): 1167

Contacts and Locations

• Study Contact: Name: Hyun-Jong Lee, MD, PhD; Phone Number: 82-10-6217-9315; Email: untouchables00@hanmail.net
• Study Contact Backup: Name: Su Jung Lee, RN; Phone Number: 82-32-340-1812; Email: bjwwoki0827@daum.net

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Bucheon, Gyeonggi-do, Korea, Republic of, 14574
      • Recruiting
      • Sejong general hospital, 91-121 Sosa 2-Dong, Sosa-Gu
      • Contact: Hyun-Jong Lee, MD, PhD; Phone Number: 82-10-6217-9315; Email: untouchables@sejongh.co.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with intermediate coronary artery stenosis, who need functional evaluation

Description

Inclusion Criteria:

• Patients with intermediate coronary artery stenosis (visually 50-90% diameter stenosis) who decided to undergoing a RFR-guided coronary intervention according to clinical necessity
• Patients who voluntarily decided to participate in this study and signed informed consent

Exclusion Criteria:

• Severe left ventricular systolic dysfunction (LVEF <30%)
• Cardiogenic shock
• Culprit vessel in acute coronary syndrome
• Donor vessel to supply chronic total occlusion lesion of non-target vessel
• Symptomatic valvular heart disease or cardiomyopathy
• Hemodynamic instability at the time of intervention (heart rate <50 beats per minute, systolic blood pressure <90mmHg)
• Previous CABG with patent grafts to the interrogated vessel
• Pregnancy or breastfeeding
• Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
A composite of death from any cause, non-fatal myocardial infarction, or unplanned revascularization	At 2-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target lesion failure	A composite of cardiac death, target vessel MI, or target lesion revascularization	At 2-year
Target vessel failure	A composite of cardiac death, target vessel MI, or target vessel revascularization	At 2-year
Death from any cause		At 2-year
Cardiovascular death		At 2-year
Cardiac death or non-fatal MI		At 2-year
Non-fatal MI		At 2-year
Any unplanned revascularization		At 2-year
Target vessel revascularization		At 2-year
Target lesion revascularization		At 2-year

Collaborators and Investigators

• Sponsor: Sejong General Hospital
• Collaborators: Seoul St. Mary's Hospital; Pusan National University Hospital; Ulsan University Hospital; Seoul National University Bundang Hospital; Gyeongsang National University Hospital; Keimyung University Dongsan Medical Center; Dong-A University Hospital; Soon Chun Hyang University; Wonju Severance Christian Hospital; Hospital San Carlos, Madrid; Kosin University Gospel Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 3, 2023
• First Submitted That Met QC Criteria: October 3, 2023
• First Posted (Estimated): October 10, 2023

Study Record Updates

• Last Update Posted (Estimated): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: physiologic assessment; intermediate stenosis
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: COMFORT Vesion 2.6

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