Distal Evaluation of Functional Performance with Intravascular Sensors to Assess the Narrowing Effect: Guided Physiologic Stenting (DEFINE GPS)

Multi-center, prospective, randomized controlled study comparing PCI guided by angiography versus iFR Co-Registration using commercially available Philips pressure guidewires and the SyncVision co-registration system, employing an adaptive design study for interim sample size re-estimation.

Study Overview

• Status: Enrolling by invitation
• Conditions: Coronary Artery Disease; Ischemic Heart Disease
• Intervention / Treatment: Device: Philips SyncVision system with Philips pressure wires; Procedure: standard of care angiographically-guided PCI

Detailed Description

DEFINE GPS Substudy: Characterization of Intermediate Lesions (ChIL) will enroll approximately 350 patients at up to 20 sites. This multi-center, prospective, registry will enroll patients consented to be randomized into the DEFINE GPS study but ultimately screen fail. Baseline patient medical and demographic data will be collected along with angiographic and functional data from vessels with intermediate disease deferred from revascularization and will be used to establish a body of imaging data that can be used to validate new image-based physiology applications.

• Study Type: Interventional
• Enrollment (Estimated): 3212
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Gateshead, Australia
    • Lake Macquarie Private Hospital
  • Melbourne, Australia
    • The Alfred Hospital
  • New South Wales
    • Gosford, New South Wales, Australia
      • Gosford Hospital
    • Liverpool, New South Wales, Australia
      • Liverpool Hospital
    • Saint Leonards, New South Wales, Australia
      • Royal North Shore Hospital
    • Sydney, New South Wales, Australia
      • Prince of Wales Hospital
• Austria
  • Feldkirch, Austria
    • Akademisches Lehrkrankenhaus Feldkirch
• Canada
  • Brampton, Canada
    • William Osler Health-Brampton Civic Hospital
  • Montréal, Canada
    • Hopital Du Sacre-Coeur de Montreal
  • Toronto, Canada
    • St. Michael's Hospital
  • British Columbia
    • New Westminster, British Columbia, Canada
      • Royal Columbian Hospital
  • Quebec
    • Montréal, Quebec, Canada
      • Montreal Heart Institute
• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital
• France
  • Lille, France
    • CHU Lille, Institut Coeur Poumon
  • Nîmes, France
    • CHU Nîmes Caremeau
• Germany
  • Berlin, Germany, 10249
    • Vivantes Klinikum im Friedrichshain
  • Erlangen, Germany
    • Erlangen University Hospital
  • Essen, Germany
    • University Hospital Essen
  • Freiburg, Germany
    • Universitsklinik Freiburg
• Israel
  • Hadera, Israel
    • Hillel Yaffe Medical Center
  • Tel Aviv, Israel
    • Shamir Medical Center
• Italy
  • Florence, Italy
    • Careggi University Hospital
• Korea, Republic of
  • Bucheon, Korea, Republic of
    • Sejong General Hospital
  • Daegu, Korea, Republic of
    • Keimyung University Dongsan Medical Center
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
• Mexico
  • Querétaro, Mexico
    • Hospital General Querétaro
• Netherlands
  • Dordrecht, Netherlands
    • Albert Schweitzer Ziekenhuis / Hartcentum Dordrecht- Gorinchem
  • Enschede, Netherlands
    • Medisch Spectrum Twente
  • Leeuwarden, Netherlands
    • Medisch Centrum Leeuwarden
  • Nieuwegein, Netherlands
    • St Antonius Hospital Nieuwegein
  • Nijmegen, Netherlands
    • Radboud University Med Ctr
• Poland
  • Warsaw, Poland
    • Medical University of Warsaw
• Portugal
  • Amadora, Portugal
    • Hospital Prof. Doutour Fernando Foneseca
• Spain
  • Córdoba, Spain
    • Hospital Universitario Reina Sofía
  • León, Spain
    • Hospital Universitario de Leon
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Santander, Spain
    • Hospital Universitario Marqués de Valdecillas
• Sweden
  • Lund, Sweden
    • Skåne University Hospital
  • Örebro, Sweden
    • Orebro University Hospital
• Switzerland
  • Geneva, Switzerland
    • Geneva University Hospital
• United Kingdom
  • Bournemouth, United Kingdom
    • Royal Bournemouth Hospital
  • London, United Kingdom
    • Imperial College Healthcare NHS Trust
  • Hampshire
    • Southampton, Hampshire, United Kingdom, S016 6YD
      • University Hospital Southampton
  • Wales
    • Cardiff, Wales, United Kingdom
      • University Hospital of Wales
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85716
      • Pima Heart & Vascular
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Central Arkansas Veterans Healthcare System (CAVHS)
  • California
    • Glendale, California, United States, 91206
      • Glendale Adventist
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Colorado Heart and Vascular
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Florida
    • Hollywood, Florida, United States, 33201
      • Memorial Healthcare
    • Tampa, Florida, United States, 33607
      • Tampa Cardiovascular Innovations and Research
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Straub Medical Center
  • Illinois
    • Urbana, Illinois, United States, 61801
      • Carle Foundation Hospital
  • Indiana
    • Munster, Indiana, United States, 46321
      • Community Healthcare System
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Mass General
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Metro Cardiology Consultants
    • Edina, Minnesota, United States, 55435
      • Fairview Health Services
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Buffalo, New York, United States, 14203
      • Gates Vascular Institute
    • Lake Success, New York, United States, 11042
      • Northwell Health
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • NC Heart and Vascular Research, LLC
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Philadelphia, Pennsylvania, United States, 19141
      • Jefferson Einstein Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • North Central Heart
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Centennial Medical Center
    • Nashville, Tennessee, United States, 37205
      • Ascension Saint Thomas
  • Texas
    • Plano, Texas, United States, 75093
      • Baylor Scott & White, The Heart Hospital Plano
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Sentara Health
    • Roanoke, Virginia, United States, 24014
      • Carilion Clinic
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Health

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Adult men and women (local age of consent) who present with stable or unstable angina, or NSTEMI.
• 2. Undergoing cardiac catheterization with planned PCI or possible ad hoc PCI

• 3. Following angiography, PCI is indicated in at least one coronary artery* on the basis of one or more of the following:

  1. Presenting with NSTE-ACS (unstable angina with ECG changes or cardiac enzyme-positive NSTEMI) with an identified culprit lesion with DS ≥50%;
  2. One or more angiographic stenoses present with ≥80% stenosis severity by visual estimation;
  3. One or more angiographic stenoses present with ≥50% to <80% stenosis severity by visual estimation and an abnormal non-invasive stress test in the distribution of the lesion(s) within the past 60 days;
  4. One or more angiographic stenoses are present with ≥50% to <80% stenosis severity by visual estimation and a spot iFR measure ≤0.89 or FFR≤0.80 for borderline iFR..
• 4 Subject is willing to comply with all scheduled visits and tests and has provided informed written consent

Exclusion Criteria:

• 1. STEMI within 30 days
• 2. PCI within the prior 12 months, or any PCI planned after the study procedure (other than planned staged procedures of randomized vessels which are allowed)
• 3. Prior CABG anytime
• 4. Silent ischemia only (i.e. no cardiac symptoms related to coronary artery disease) within the prior 4 weeks
• 5. Documented prior iFR pullback performed in any coronary artery including during the qualifying diagnostic angiogram
• 6. Any vessel with in-stent restenosis (ISR) requiring treatment
• 7. Cardiogenic shock defined as systolic blood pressure <90 mmHg for >20 minutes not responding to fluid resuscitation, or need for inotropic, pressor, or device-based hemodynamic support
• 8. Presence of unstable ventricular arrhythmias
• 9. Heart rate > 110, including uncontrolled atrial fibrillation (AF)
• 10. Decompensated congestive heart failure (NYHA Class IV or Killip Class III or IV)
• 11. Chronic total occlusion (CTO) of a target vessel (exception: a CTO may be present in a non-target vessel if it is supplying non-viable myocardium and there is no intent to open the CTO during the index or later procedure)
• 12. Coronary anatomy not amenable to pressure wire manipulation due to extreme tortuosity or complexity such that it is unlikely that a pressure wire could be passed to the distal third of the three major epicardial coronary arteries
• 13. Any angiographic giant thrombus (i.e., thrombus length > 3x RVD at lesion)
• 14. Any target vessel with < TIMI III flow
• 15. Any target lesion with a reference vessel diameter (RVD) less than 2.25mm except for within the side branch of a bifurcation lesion
• 16. Any non-target lesion with a reference vessel diameter (RVD) greater than 2.00mm that contains an ≥80% stenosis and is not intended for treatment with PCI (other than a CTO supplying non-viable myocardium - see exclusion #11)
• 17. Known severe aortic or mitral valve stenosis/insufficiency
• 18. Known non-cardiovascular comorbidity resulting in lifespan <24 months
• 19. Known left ventricular ejection fraction ≤30%
• 20. Estimated creatinine clearance (MDRD formula) <30 mL/min/1.73m2 or on dialysis
• 21. Any cardiac or non-cardiac surgical procedure planned within 12 months after enrollment, or any procedure planned within 6 months after enrollment that would necessitate discontinuation of dual antiplatelet therapy
• 22. Known pregnancy or planning to become pregnant (women of child-bearing potential must have a negative pregnancy test within 1 week of enrollment)
• 23. Participating in another investigational drug or device study that has not reached its primary endpoint
• 24. Any condition such as dementia or substance abuse that may impair the patient's ability to comply with all study procedures, including medication compliance and follow-up visits
• 25. Patient is a member of a vulnerable population who, in the judgment of the investigator, is unable to give Informed Consent for reasons of incapacity, immaturity, adverse personal circumstances or lack of autonomy. This may include individuals with mental disability, persons in nursing homes, children, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those permanently incapable of giving informed consent. Vulnerable populations also include university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces, and persons kept in detention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: physiologically-guided arm; Physiologically-guided PCI using the Philips SyncVision system for determining the PCI strategy	Device: Philips SyncVision system with Philips pressure wires; Intent to use physiologically-guided PCI using the Philips SyncVision system for determining the PCI strategy
Active Comparator: angiographically-guided arm; Standard of care angiographically-guided PCI for determining the PCI strategy	Procedure: standard of care angiographically-guided PCI; Intent to use PCI standard of care angiographically-guided PCI for determining the PCI strategy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Major Adverse Cardiac Events (MACE; composite of cardiac death, target vessel MI (TVMI), or ischemia-driven revascularization) or hospitalization for progressive or unstable angina at 2 years	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause, cardiac and non-cardiac mortality		30 days, 1 year and 2 years
All MI, target vessel MI, non-target vessel MI, procedural MI, non-procedural MI		30 days, 1 year and 2 years
Ischemia-driven revascularization, including all revascularization, TVR, TLR, non-TLR TVR, and non-TVR		30 days, 1 year and 2 years
Hospitalization for progressive or unstable ischemia		30 days, 1 year and 2 years
Stent thrombosis (definite, probable and definite/probable)		30 days, 1 year and 2 years
Angina-related Quality of Life	Change from baseline in the Seattle Angina Questionnaire (SAQ-7) summary score	30 days, 1 year and 2 years
Resource utilization	The [US-based] cost of all health care resources associated with the index procedure and pre-specified event costs throughout the two-year follow up period	30 days, 1 year and 2 years
Cost effectiveness	Cost per quality-adjusted life years gained	30 days, 1 year and 2 years
Major Adverse Cardiac Events (MACE; composite of cardiac death, target vessel MI (TVMI), or ischemia-driven revascularization) or hospitalization for progressive or unstable angina		30 days, 1 year

Collaborators and Investigators

• Sponsor: Philips Clinical & Medical Affairs Global
• Investigators: Study Chair: Gregg W Stone, MD, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai; Principal Investigator: Allen Jeremias, MD MSC FACC FSCAI, Saint Francis Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: June 25, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia
• Other Study ID Numbers: 190103

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: Yes
• product manufactured in and exported from the U.S.: Yes