Fractional Flow Reserve or 3D-Quantitative-Coronary-Angiography Based Vessel-FFR Guided Revascularization (FAST III)

The FAST III is a randomized controlled, open-label, multicenter, international, non-inferiority, strategy trial. A total of 2228 participants will be randomized in a 1:1 fashion to either vFFR- or FFR guided revascularization. Patients will be consented prior to the procedure and then followed up to 12 (+1) months after randomization. The primary endpoint is analyzed at 12 months after randomization. Approximately 35 sites in 7 European countries (Netherlands, Ireland, United Kingdom, Germany, Italy, Spain, and France).

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: vFFR guided revascularization; Device: FFR guided revascularization

Detailed Description

The FAST III is a randomized controlled, open-label, multicenter, international, non-inferiority, strategy trial of a vFFR guided strategy as compared to a FFR guided strategy to guide coronary revascularization in 2228 subjects with intermediate coronary artery lesions.

Patients are screened for inclusion/exclusion criteria after the indication for coronary catheterization is established. After providing informed consent, patients are enrolled. Randomization is performed in the randomization module of the EDC system with an allocation ratio of 1:1 and stratification by center. The primary endpoint is a composite of all-cause death, any myocardial infarction, or any revascularization at 1 year post-randomization.

All deaths and major cardiovascular events, including the individual components of primary and secondary endpoints are adjudicated by an independent Clinical Events Committee (CEC), using standardized definitions. An independent Data and Safety Monitoring Board (DSMB) will formally review the accumulating data to ensure there is no avoidable increased risk for harm to participants. The FAST III trial is performed in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP), ISO 14155:2020, EC requirements and country specific regulations.

• Study Type: Interventional
• Enrollment (Estimated): 2228
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ernest Spitzer, MD; Phone Number: +31102062828; Email: E.Spitzer@ECRI-Trials.com
• Study Contact Backup: Name: Monique Schuijer, PhD; Phone Number: +31102062828; Email: MSchuijer@cardialysis.nl

Study Locations

• France
  • Caen, France
    • Recruiting
    • Clinique St Martin
    • Principal Investigator: Jean Fancois Morelle, MD, PhD
  • Grenoble, France
    • Not yet recruiting
    • Institut Cardiovasculaire de Grenoble
    • Principal Investigator: Benjamin Faurie, MD, PhD
  • Lille, France
    • Recruiting
    • CHU Lille - Institut Coeur Poumon
    • Principal Investigator: Eric van Belle, MD, PhD
  • Lyon, France
    • Recruiting
    • Hôpital de la Croix Rousse, Hospices Civils de Lyon
    • Principal Investigator: Brahim Harbaoui, MD, PhD
  • Massy, France
    • Not yet recruiting
    • Hôpital privé Jacques Cartier
    • Principal Investigator: Thomas HOVASSE, MD, PhD
  • Melun, France
    • Recruiting
    • Clinique les Fontaines
    • Principal Investigator: Patrick Dupouy, MD, PhD
  • Rouen, France
    • Recruiting
    • Clinique Saint Hilaire
    • Principal Investigator: Matthieu Godin, MD, PhD
• Germany
  • Bad Oeynhausen, Germany
    • Recruiting
    • Herz- und Diabeteszentrum NRW
    • Principal Investigator: Regine Brinkmann, MD, PhD
  • Berlin, Germany
    • Recruiting
    • Unfallkrankenhaus Berlin
    • Principal Investigator: Steffen Bohl, MD, PhD
  • Berlin, Germany
    • Recruiting
    • Charité- Campus Benjamin Franklin
    • Principal Investigator: Ulf Landmesser, MD, PhD
  • Düsseldorf, Germany
    • Not yet recruiting
    • Universitätsklinikum Düsseldorf
    • Principal Investigator: Georg Wolff, MD, PhD
  • Neuwied, Germany
    • Recruiting
    • Marienhaus Klinikum
    • Principal Investigator: Burkhard Huegl, MD, PhD
  • Völklingen, Germany
    • Recruiting
    • SHG Klinik Völklingen
    • Principal Investigator: Fernando Gatto, MD, PhD
• Ireland
  • Cork, Ireland
    • Recruiting
    • Mater Private Cork
    • Principal Investigator: Ronan Margey, MD, PhD
  • Dublin, Ireland
    • Recruiting
    • Mater Private Dublin
    • Principal Investigator: Robert Byrne, MD, PhD
  • Dublin, Ireland
    • Withdrawn
    • Beaumont Hospital
  • Dublin, Ireland
    • Recruiting
    • St James Hospital
    • Principal Investigator: John Cosgrave, MD, PhD
• Italy
  • Bergamo, Italy
    • Recruiting
    • Azienda Ospedaliera Papa Giovanni XXIII
    • Principal Investigator: Paolo Canova, MD, PhD
  • Cona, Italy
    • Recruiting
    • AOU di Ferrara (Ospedale Sant'Anna)
    • Principal Investigator: Simone Biscaglia, MD, PhD
  • Mestre, Italy
    • Recruiting
    • Cardiologia Ospedale Dell' Angelo
    • Principal Investigator: Marco Barbierato, MD, PhD
  • Milan, Italy
    • Recruiting
    • Humanitas Research Hospital
    • Principal Investigator: Antonio Mangieri, MD, PhD
  • Milan, Italy
    • Recruiting
    • Policlínico San Donato
    • Principal Investigator: Luca Testa, Md, PhD
  • Naples, Italy
    • Not yet recruiting
    • Pineta Grande Hospital
    • Principal Investigator: Arturo Giordano, MD, PhD
  • Novara, Italy
    • Recruiting
    • Ospedale Maggiore della Carita
    • Principal Investigator: Domenico D'Amario, MD, PhD
  • Verona, Italy
    • Withdrawn
    • AOU Verona
  • Vicenza, Italy
    • Recruiting
    • Cardiologia Ospedale San Bortolo
    • Principal Investigator: Flavio Ribichini, MD, PhD
• Netherlands
  • Blaricum, Netherlands
    • Recruiting
    • Tergooi MC
    • Principal Investigator: Rutger van Bommel, MD, PhD
  • Breda, Netherlands
    • Recruiting
    • Amphia ziekenhuis
    • Principal Investigator: Martijn Meuwissen., MD, PhD
  • Dordrecht, Netherlands
    • Recruiting
    • Albert Schweitzer
    • Principal Investigator: Rohit Oemrawsing, MD, PhD
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus University Medical Center
    • Contact: Joost Daemen, MD, PhD; Email: j.daemen@erasmusmc.nl
  • Utrecht, Netherlands
    • Recruiting
    • UMCU
    • Principal Investigator: Michiel Voskuil, MD, PhD
• Spain
  • A Coruña, Spain
    • Recruiting
    • Hospital Univeritario A Coruna
    • Principal Investigator: Pablo Piñón Esteban, MD, PhD
  • Barcelona, Spain
    • Recruiting
    • Hospital Clinic
    • Principal Investigator: Manel Sabate, MD, PhD
  • Barcelona, Spain
    • Recruiting
    • Hospital del Mar
    • Principal Investigator: Beatriz Vaquerizo, MD, PhD
  • León, Spain
    • Not yet recruiting
    • Hospital Universitario de Leon
    • Principal Investigator: Maria Thiscal López Lluva, MD, PhD
  • Madrid, Spain
    • Recruiting
    • La Paz
    • Principal Investigator: Raul Moreno, MD, PhD
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario de La Princesa
    • Principal Investigator: Fernando Rivero, MD, PhD
  • Oviedo, Spain
    • Recruiting
    • Hospital Universitario Central de Asturias
    • Principal Investigator: Pablo Avanzas, MD, PhD
  • Valladolid, Spain
    • Recruiting
    • Hospital Clinico Universitario de Valladolid
    • Principal Investigator: Ignacio Amat Santos, MD, PhD
• United Kingdom
  • Belfast, United Kingdom
    • Withdrawn
    • Royal Victoria Hospital
  • Brighton, United Kingdom
    • Recruiting
    • Royal Sussex County Hospital
    • Principal Investigator: James Cockburn, MD, PhD
  • Glasgow, United Kingdom
    • Recruiting
    • Golden Jubilee National Hospital
    • Principal Investigator: Damien Collison, MD, PhD
  • Oxford, United Kingdom
    • Recruiting
    • John Radcliffe Hospital
    • Principal Investigator: Adrian Banning, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The patient must be ≥18 years of age
2. Presenting with silent ischemia, stable angina, or non-ST-elevation acute coronary syndrome (NSTE-ACS)
3. Coronary artery disease with at least one native artery in which the stenosis severity is questionable (typically 30-80% stenosis)
4. FFR assessment and vFFR assessment feasible
5. The patient is willing and able to cooperate with study procedures and follow-up until study completion
6. Subject is able to confirm understanding of risks, benefits and treatment alternatives and he/she provides informed consent prior to any protocol-related procedure, as approved by the appropriate Ethics Committee

Exclusion Criteria:

1. ST-elevation myocardial infarction (STEMI) at presentation
2. Cardiogenic shock or severe hemodynamic instability at the time of intervention (heart rate<50 beats per minute, systolic blood pressure <90mmHg) or use of left ventricular assist device
3. Any target vessel with a distal Thrombolysis In Myocardial Infarction (TIMI) flow <3.
4. Presence of thrombus in intermediate target lesion.
5. Known untreated severe valvular heart disease
6. Target lesion is located in or supplied by an arterial or venous bypass graft
7. History of cardiac allograft transplantation
8. Aorto-ostial lesions with an estimated diameter stenosis >50%
9. Severe tortuosity precluding the acquisitions of 2 orthogonal projections of the target vessel with minimal overlap or foreshortening.
10. Absolute contraindications or allergy that cannot be pre-medicated, to iodinated contrast or adenosine
11. Non-cardiac co-morbidities with a life expectancy less than 1 year
12. Currently participating in another trial that is not yet at its primary endpoint. The patient is not allowed to participate in another investigational device or drug study until the trial primary endpoint time point is achieved and may only be enrolled once in the study
13. Women of childbearing potential who do not have a negative pregnancy test within 24 hours before the procedure
14. Subject belongs to a vulnerable population (per Investigator's judgment) or subject unable to read or write

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vFFR guided revascularization	Device: vFFR guided revascularization; 3D-angio-based vessel FFR (CAAS, Pie Medical Imaging, Maastricht, The Netherlands) uses 3-Dimensional Quantitative Coronary Angiography (3D-QCA) for functional assessment of coronary stenosis. vFFR is calculated using two angiographic views with at least 30 degrees difference in rotation/angulation to generate the 3D reconstruction of the coronary artery.
Active Comparator: FFR guided revascularization	Device: FFR guided revascularization; Fractional flow reserve (FFR) is a technique used in coronary catheterization to measure pressure differences across a coronary artery stenosis (narrowing, usually due to atherosclerosis) to determine the likelihood that the stenosis impedes oxygen delivery to the heart muscle (myocardial ischemia)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of the composite of all-cause death, any myocardial infarction, or any revascularization	Procedural myocardial infarction (MI) is adjudicated according to the ARC-2 consensus and spontaneous MI according to the 4th Universal definition of MI.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of patient-oriented composite endpoint (POCE) defined as all-cause death, any stroke, any myocardial infarction, and any revascularization	1 year
Rate of device-oriented composite endpoint (DOCE) defined as the composite of cardiovascular death, target-vessel MI, clinically indicated repeat revascularization of the target lesion	1 year
Rate of study-oriented composite endpoint (SOCE) defined as the composite of cardiovascular death, study-vessel or target vessel MI, or study-vessel or target vessel revascularization	1 year
Rate of target-vessel failure defined as a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target-vessel revascularization	1 year
Rate of target-lesion failure defined as a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target-lesion revascularization	1 year
Rate of study-vessel failure defined as a composite of cardiac death, study vessel myocardial infarction, or clinically indicated study-vessel revascularization	1 year
Rate of definite and probable stent thrombosis	1 year

Other Outcome Measures

Outcome Measure	Time Frame
Quality of life (QoL) using the Seattle Angina Questionnaire	1 month and 1 year
Procedural time	Baseline
Total contrast volume	Baseline
Fluoroscopy time	Baseline
Radiation dose	Baseline

Collaborators and Investigators

• Sponsor: ECRI bv
• Collaborators: Siemens Healthineers AG; Pie Medical Imaging
• Investigators: Principal Investigator: Joost Daemen, MD, PhD, Erasmus Medical Center; Study Director: Ernest Spitzer, MD, European Cardiovascular Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2021
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: June 11, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Coronary artery disease; Intermediate coronary lesion; Coronary physiology; vFFR
• 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: ECRI-15

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