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

Overview

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.

Interventions

• Device Philips SyncVision system with Philips pressure wires
  Intent to use physiologically-guided PCI using the Philips SyncVision system 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

Primary outcome measures

• 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 [Time frame: 2 years]

Secondary outcome measures (9)

• Major Adverse Cardiac Events (MACE; composite of cardiac death, target vessel MI (TVMI), or ischemia-driven revascularization) or hospitalization for progressive or unstable angina [Time frame: 30 days, 1 year]
• All-cause, cardiac and non-cardiac mortality [Time frame: 30 days, 1 year and 2 years]
• All MI, target vessel MI, non-target vessel MI, procedural MI, non-procedural MI [Time frame: 30 days, 1 year and 2 years]
• Ischemia-driven revascularization, including all revascularization, TVR, TLR, non-TLR TVR, and non-TVR [Time frame: 30 days, 1 year and 2 years]
• Hospitalization for progressive or unstable ischemia [Time frame: 30 days, 1 year and 2 years]
• Stent thrombosis (definite, probable and definite/probable) [Time frame: 30 days, 1 year and 2 years]
• Angina-related Quality of Life [Time frame: 30 days, 1 year and 2 years]
• Resource utilization [Time frame: 30 days, 1 year and 2 years]
• Cost effectiveness [Time frame: 30 days, 1 year and 2 years]

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:

• Presenting with NSTE-ACS (unstable angina with ECG changes or cardiac enzyme-positive NSTEMI) with an identified culprit lesion with DS ≥50%;
• One or more angiographic stenoses present with ≥80% stenosis severity by visual estimation;
• 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;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 40 centers

• University of Alabama Birmingham — Birmingham
• Pima Heart & Vascular — Tucson
• Central Arkansas Veterans Healthcare System (CAVHS) — Little Rock
• Glendale Adventist — Glendale
• Colorado Heart and Vascular — Lakewood
• Yale University — New Haven
• MedStar Washington Hospital Center — Washington D.C.
• Memorial Healthcare — Hollywood
• … and 32 more centers

Australia · 6 centers

• Gosford Hospital — Gosford
• Liverpool Hospital — Liverpool
• Royal North Shore Hospital — Saint Leonards
• Prince of Wales Hospital — Sydney
• Lake Macquarie Private Hospital — Gateshead
• The Alfred Hospital — Melbourne

Canada · 5 centers

• Royal Columbian Hospital — New Westminster
• Montreal Heart Institute — Montreal
• William Osler Health-Brampton Civic Hospital — Brampton
• Hopital du Sacre-Coeur de Montreal — Montreal
• St. Michael's Hospital — Toronto

Netherlands · 5 centers

• Albert Schweitzer Ziekenhuis / Hartcentum Dordrecht- Gorinchem — Dordrecht
• Medisch Spectrum Twente — Enschede
• Medisch Centrum Leeuwarden — Leeuwarden
• St Antonius Hospital Nieuwegein — Nieuwegein
• Radboud University Med Ctr — Nijmegen

Germany · 4 centers

• Vivantes Klinikum im Friedrichshain — Berlin
• Erlangen University Hospital — Erlangen
• University Hospital Essen — Essen
• Universitsklinik Freiburg — Freiburg im Breisgau

Spain · 4 centers

• Hospital Universitario Reina Sofía — Córdoba
• Hospital Universitario de Leon — León
• Hospital Clinico San Carlos — Madrid
• Hospital Universitario Marqués de Valdecillas — Santander

United Kingdom · 4 centers

Center list to be confirmed — check the primary protocol.

South Korea · 3 centers

• Sejong General Hospital — Bucheon-si
• Keimyung University Dongsan Medical Center — Daegu
• Seoul National University Hospital — Seoul

France · 2 centers

• CHU Lille, Institut Coeur Poumon — Lille
• CHU Nimes Caremeau — Nîmes

Israel · 2 centers

• Hillel Yaffe Medical Center — Hadera
• Shamir Medical Center — Tel Aviv

Sweden · 2 centers

• Skane University Hospital — Lund
• Örebro University Hospital — Örebro

Austria · 1 center

• Akademisches Lehrkrankenhaus Feldkirch — Feldkirch

Denmark · 1 center

• Aarhus University Hospital — Aarhus

Italy · 1 center

• Careggi University Hospital — Florence

Mexico · 1 center

• Hospital General Querétaro — Querétaro

Poland · 1 center

• Medical University of Warsaw — Warsaw

Portugal · 1 center

• Hospital Prof. Doutour Fernando Foneseca — Amadora

Switzerland · 1 center

• Geneva University Hospital — Geneva

Identifiers

NCT: NCT04451044 · 190103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗