Clinical trial NCT04451044: Distal Evaluation of Functional Performance with Intravascular Sensors to Assess the Narrowing Effect: Guided Physiologic Stenting
Official title: Distal Evaluation of Functional Performance with Intravascular Sensors to Assess the Narrowing Effect: Guided Physiologic Stenting
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Coronary Artery Disease
Ischemic Heart Disease
Lead sponsor: Philips Clinical & Medical Affairs Global
Sponsor class: INDUSTRY
First posted: 2020-06-30
Enrollment: 3212
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 2 years
Secondary outcomes:
measure: Major Adverse Cardiac Events (MACE; composite of cardiac death, target vessel MI (TVMI), or ischemia-driven revascularization) or hospitalization for progressive or unstable angina
timeFrame: 30 days, 1 year
measure: All-cause, cardiac and non-cardiac mortality
timeFrame: 30 days, 1 year and 2 years
measure: All MI, target vessel MI, non-target vessel MI, procedural MI, non-procedural MI
timeFrame: 30 days, 1 year and 2 years
measure: Ischemia-driven revascularization, including all revascularization, TVR, TLR, non-TLR TVR, and non-TVR
timeFrame: 30 days, 1 year and 2 years
measure: Hospitalization for progressive or unstable ischemia
timeFrame: 30 days, 1 year and 2 years
measure: Stent thrombosis (definite, probable and definite/probable)
timeFrame: 30 days, 1 year and 2 years
measure: Angina-related Quality of Life
timeFrame: 30 days, 1 year and 2 years
measure: Resource utilization
timeFrame: 30 days, 1 year and 2 years
measure: Cost effectiveness
timeFrame: 30 days, 1 year and 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Tucson
country: United States
facility: Pima Heart & Vascular
state: Arizona
city: Little Rock
country: United States
facility: Central Arkansas Veterans Healthcare System (CAVHS)
state: Arkansas
city: Glendale
country: United States
facility: Glendale Adventist
state: California
city: Lakewood
country: United States
facility: Colorado Heart and Vascular
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Hollywood
country: United States
facility: Memorial Healthcare
state: Florida
city: Tampa
country: United States
facility: Tampa Cardiovascular Innovations and Research
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Honolulu
country: United States
facility: Straub Medical Center
state: Hawaii
city: Urbana
country: United States
facility: Carle Foundation Hospital
state: Illinois
city: Munster
country: United States
facility: Community Healthcare System
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Mass General
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Coon Rapids
country: United States
facility: Metro Cardiology Consultants
state: Minnesota
city: Edina
country: United States
facility: Fairview Health Services
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Buffalo
country: United States
facility: Gates Vascular Institute
state: New York
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Raleigh
country: United States
facility: NC Heart and Vascular Research, LLC
state: North Carolina
city: Akron
country: United States
facility: Summa Health System
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Einstein Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: North Central Heart
state: South Dakota
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Ascension Saint Thomas
state: Tennessee
city: Plano
country: United States
facility: Baylor Scott & White, The Heart Hospital Plano
state: Texas
city: Norfolk
country: United States
facility: Sentara Health
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: La Crosse
country: United States
facility: Gundersen Health
state: Wisconsin
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Gateshead
country: Australia
facility: Lake Macquarie Private Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Feldkirch
country: Austria
facility: Akademisches Lehrkrankenhaus Feldkirch
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Brampton
country: Canada
facility: William Osler Health-Brampton Civic Hospital
city: Montréal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
city: Toronto
country: Canada
facility: St. Michael's Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Lille
country: France
facility: CHU Lille, Institut Coeur Poumon
city: Nîmes
country: France
facility: CHU Nimes Caremeau
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Erlangen
country: Germany
facility: Erlangen University Hospital
city: Essen
country: Germany
facility: University Hospital Essen
city: Freiburg
country: Germany
facility: Universitsklinik Freiburg
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Tel Aviv
country: Israel
facility: Shamir Medical Center
city: Florence
country: Italy
facility: Careggi University Hospital
city: Bucheon
country: Korea, Republic of
facility: Sejong General Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Querétaro
country: Mexico
facility: Hospital General Querétaro
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis / Hartcentum Dordrecht- Gorinchem
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Nieuwegein
country: Netherlands
facility: St Antonius Hospital Nieuwegein
city: Nijmegen
country: Netherlands
facility: Radboud University Med Ctr
city: Warsaw
country: Poland
facility: Medical University of Warsaw
city: Amadora
country: Portugal
facility: Hospital Prof. Doutour Fernando Foneseca
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: León
country: Spain
facility: Hospital Universitario de Leon
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecillas
city: Lund
country: Sweden
facility: Skane University Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
city: Geneva
country: Switzerland
facility: Geneva University Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
state: Hampshire
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Saint Francis Hospital
name: Allen Jeremias, MD MSC FACC FSCAI
role: PRINCIPAL_INVESTIGATOR
affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
name: Gregg W Stone, MD
role: STUDY_CHAIR
References: