Clinical trial NCT05648396: Japan FFRangio Clinical Outcomes Study
Official title: Japan Multicentre FFRangio Outcomes Registry
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Coronary Artery Disease
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
Collaborators: name: Gifu Heart Center
name: Fukuoka Sanno Hospital
name: Saga-ken Medical Center Koseikan
name: Sakakibara Heart Institute
name: Fukuyama Cardiovascular Hospital
name: Ichinomiya-Nishi Hospital
First posted: 2022-12-13
Enrollment: 2500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: all comers patients undergoing coronary angiogram, in which FFRangio is used to assess the physiologic significance of at least one coronary lesion.

Brief summary: This study aims to collect data on clinical outcomes of real world patients undergoing FFRangio guided treatment for coronary artery disease in Japan and Israel through a retrospective multicentre registry.

Detailed description: Background:

Visual assessment of the severity of coronary stenosis is known to have a poor diagnostic accuracy for identifying functionally significant lesion \[1,2). The fractional flow reserve (FFR) is an index that quantifies the hemodynamic impact of a stenosis in an epicardial coronary artery. It is defined as the ratio of hyperemic myocardial flow in the presence of stenosis to the hyperemic flow in its absence, and is obtained by measuring the distal coronary pressure and the aortic pressure, respectively, using a pressure-measuring guidewire during maximal hyperemia \[2,3\]. Clinical outcome studies have shown that medical therapy should be preferred for non-hemodynamically significant lesions (FFR\>0.80), and coronary revascularization should be considered in cases of significant functional stenosis (FFR≤0.80) \[4-11\]. Accordingly, both American and European revascularization guidelines recommend using FFR to guide coronary revascularization, especially in stable coronary artery disease patients \[12,13\]. In spite of these recommendations, the utilization of FFR in clinical practice remains low \[14\]. Recently, methods to calculate angiogram based FFR (abFFR) (without the need for pressure wires or induction of maximal coronary hyperemia) have become available. A meta-analysis of 14 studies examining various abFFR technologies ( total of 1,842 lesions), reported a sensitivity of 89%, specificity of 90%, and a C-statistic of 0.84 compared to wire based FFR (wbFFR) \[15\], highlighting the potential for abFFR technologies to facilitate the integration of physiologic assessment into daily cathlab practice. The FFRangioTM system (CathWorks, Kfar-Saba, Israel; Figure 1), is an angiogram-derived FFR technology that has shown excellent diagnostic performance (overall accuracy 92.6%) when compared to wire based FFR in a large pooled cohort of individual patients data from 5 individual studies (588 patients, 700 lesions) \[16\]. FFRangio has already received FDA 510(k) clearance for clinical use as a stand-alone technology without the need for concurrent wire based FFR measurement \[17\]. FFRangio has been in clinical use in Japan since 2019, but there is very limited data on the clinical outcomes of FFRangio guided treatment.

Recently, the first study examining the outcomes of FFRangio guided treatment for patients undergoing angiography for suspected coronary artery disease has reported excellent 1 year results for both FFRangio guided revascularization as well as deferral \[18\], but more data is needed to more appropriately assess the technology in real world patients.

The aim of this multicenter registry is to expand the evidence base on outcomes of FFRangio guided treatment for coronary artery disease, focusing on outcomes of Japanese patients.

Methods:

A retrospective, multicenter registry of consecutive patients in whom FFRangio is used to assess the physiologic significance of at least 1 coronary lesion and guide the treatment decisions .

Inclusion criteria:

• Patients undergoing coronary angiogram for a clinical indication, for whom FFRangio is used to assess the physiologic significance of at least 1 coronary lesion and guide the treatment decisions.

Exclusion criteria:

* Culprit lesion of a STEMI (patients undergoing PCI for non-culprit lesions can be included if the culprit lesion has been successfully treated prior to the non-culprit PCI
* Presence of significant (moderate+) valvular heart disease
* Chronic total occlusion in one of the coronary arteries
* Isolated significant left main disease
* Prior coronary artery bypass graft surgery
* Clinical presentation of cardiogenic shock or severe LV dysfunction
* Coronary anomalies

Endpoints

Primary endpoint:

• composite of all cause death/myocardial infarction(MI)/repeat revascularization(RR) at 1 year follow up.

Secondary endpoints:

* The individual components of the primary endpoint
* Cardiovascular (CV) death
* Urgent RR (performed as an inpatient during an admission for ACS).
* Target vessel RR
* Target lesion RR
* Target vessel MI
* Target lesion MI

Timing of follow up:

Six and 12 months post procedure (primary analysis will include 1 year data) and yearly follow up thereafter up to 5 years.

Ascertainment and adjudications of clinical events The clinical endpoints events will be identified by the participating centres through the patients' electronic medical record and will be further verified, when possible, by interviews conducted during in person/virtual outpatient clinic visits and/or telephone follow up.

Sample size Our aim is to include up to 10 high volume FFRangio centres from Japan and Israel with a goal of reaching a sample size of at least 1,500 patients.

Ethical aspects The study will be approved by the local institutional review boards at each participating centre. Since there is no intervention in the clinical care given to the patient, waiver of the need for patient's informed consent will besought from the IRB/EC.

If participating investigators come by patients' personal information ( information on living individuals that can be used to specific individuals by name, date of birth or other description), such information shall be treated and protected under strict confidentiality. Further more participating investigators shall conduct this research in accordance with ethical principles on the Declaration of Helsinki.

Expected time frame Initiation of registry: Q4 2022 Expected data collection for 1,500 patients: Q2 2023 Initial data analysis: Q3 2023 (median follow up of 6 months for a sample size of 1,500 patients )

Eligibility criteria: Inclusion criteria:

• Patients undergoing coronary angiogram for a clinical indication, for whom FFRangio is used to assess the physiologic significance of at least 1 coronary lesion and guide the treatment decisions.

Exclusion criteria:

* Culprit lesion of a STEMI (patients undergoing PCI for non-culprit lesions can be included if the culprit lesion has been successfully treated prior to the non-culprit PCI
* Presence of significant (moderate+) valvular heart disease
* Chronic total occlusion in one of the coronary arteries
* Isolated significant left main disease
* Prior coronary artery bypass graft surgery
* Clinical presentation of cardiogenic shock or severe LV dysfunction
* Coronary anomalies

Primary outcomes:
measure: composite of Cardio-Vascular(CV) mortality/Myocardial infarction (MI)/Repeat revascularization
timeFrame: 1 year
Secondary outcomes:
measure: Overall death
timeFrame: 1 year
measure: Cardio Vascular death
timeFrame: 1 year
measure: MyocardiaI infarction (MI)
timeFrame: 1 year
measure: Repeat revascularization
timeFrame: 1 year
measure: Urgent repeat revascularization
timeFrame: 1 year
measure: target vessel repeat revascularization
timeFrame: 1 year
measure: Target lesion repeat revascularization
timeFrame: 1 year
measure: Target vessel MI
timeFrame: 1 year
measure: Target lesion MI
timeFrame: 1 year
Other outcomes:
Locations:
city: Petah tikva
country: Israel
facility: Rabin Medical Centre
Study officials:
affiliation: Rabin Medical Centre
name: Guy Witberg, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: