Physiologic Assessment of Coronary Stenosis Following PCI (DEFINE PCI)

DEFINE PCI: Physiologic Assessment of Coronary Stenosis Following PCI

This is a pilot study designed to assess the relationship between iFR (instantaneous wave-free ratio) pullback and the distribution of coronary atheroma/stenoses as assessed by Quantitative Coronary Angiography (QCA) post angiographically successful PCI (Percutaneous Coronary Intervention).

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Angina, Stable; Angina, Unstable; Coronary Stenosis
• Intervention / Treatment: Diagnostic test: iFR pullback

Detailed Description

DEFINE-PCI is a multi-center, prospective, non-significant risk study in up to 25 centers in USA and internationally. Consented subjects with CAD (Coronary Artery Disease) who undergo physiologic lesion assessment with iFR<0.90 in at least 1 coronary artery are eligible for participation. After successful PCI to all culprit lesions based on angiographic assessment of the treating physician, a blinded post-PCI iFR and iFR pullback will be performed. The proportion of patients with impaired post-PCI iFR will be assessed, and the number of patients in whom ischemia could theoretically be normalized with further PCI determined. Additionally, the association between the post-PCI iFR results and cardiovascular events and clinical symptoms will be assessed. Follow-up will be at 1, 6 and 12 months, including administration of quality of life questionnaires.

• Study Type: Observational
• Enrollment (Actual): 500

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • VU University Medical Center
  • Amsterdam, Netherlands
    • AMC Amsterdam
• United Kingdom
  • Basildon, United Kingdom, SS165NL
    • Basildon Univeristy Hospital
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth Hospital
  • Exeter, United Kingdom, EX25DW
    • Royal Devon & Exeter NHS Foundation Trust
  • London, United Kingdom, W12OHS
    • Imperial College of London- Hammersmith Hospital
• United States
  • California
    • Long Beach, California, United States, 90822
      • VA Medical Center
  • Colorado
    • Lakewood, Colorado, United States, 80204
      • Colorado Heart and Vascular
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical Center
  • Illinois
    • Rockford, Illinois, United States, 61107
      • Rockford CV Associates
  • Iowa
    • Davenport, Iowa, United States, 52803
      • Midwest Cardiovascular Research Foundation
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock
  • New York
    • Bay Shore, New York, United States, 11706
      • South Side Hospital
    • Manhasset, New York, United States, 11030
      • NorthShore Hospital
    • New York, New York, United States, 10075
      • Lenox Hill Hospital
    • New York, New York, United States, 10032
      • Columbia University Medical Center/NewYork Presbyterian Hospital
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital -Weill Cornell
    • Roslyn, New York, United States, 11576
      • St Francis Hospital
    • Stony Brook, New York, United States, 11794
      • SUNY- Stony Brook
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital
    • Greenville, North Carolina, United States, 27835
      • Vidant Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Miriam Hospital
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont CVA Heart Insitute
  • Texas
    • Dallas, Texas, United States, 75216
      • VA North Texas Health Care
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St Lukes Medical Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Consented subjects with CAD who undergo physiologic lesion assessment with iFR<0.90 in at least 1 coronary artery are eligible for participation

Description

Inclusion Criteria:

1. Subject must be > 18 years old
2. Subjects presenting with stable angina, silent ischemia or non-ST-elevation ACS (acute coronary syndrome) (unstable angina or biomarker positive)
3. Single vessel CAD with at least 2 separate lesions (≥10 mm apart) of ≥40% stenosis or a single long lesion of ≥20mm OR multi-vessel CAD, defined as at least 2 vessels with ≥40% stenosis
4. Pre-PCI iFR performed in all vessels intended for PCI
5. Pre-PCI iFR of <0.90 of at least 1 stenosis
6. Subjects are able and willing to comply with scheduled visits and tests and to provide informed consent.

Exclusion Criteria:

1. Pregnant or planning to become pregnant for the duration of the study
2. Acute STEMI (ST-elevated Myocardial Infarction) within the past 7 days
3. Cardiogenic shock (sustained (>10 min) systolic blood pressure < 90 mmHg in absence of inotropic support or the presence of an intra-aortic balloon pump).
4. Ionotropic or temporary pacing requirement
5. Sustained ventricular arrhythmias
6. Prior CABG (Coronary Artery Bypass Graft)
7. Known ejection fraction ≤30%
8. Chronic Total Occlusion (CTO)
9. Known severe mitral or aortic stenosis.
10. Any known medical comorbidity resulting in life expectancy < 12 months.
11. Participation in any investigational study that has not yet reached its primary endpoint.
12. Known severe renal insufficiency (eGFR <30 ml/min/1.72 m2).
13. TIMI flow <3 at baseline
14. Intra-coronary thrombus on baseline angiography

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
iFR post angiographically successful PCI	Diagnostic test: iFR pullback; iFR pullback assessment post angiographically successful PCI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Residual Ischemia (iFR <0.90)	Residual ischemia is defined as iFR measurement <0.90 after operator-assessed angiographically successful PCI (residual diameter stenosis <50% in any treated lesion in the target vessel) This outcome describes the number of participants that had a residual ischemia (defined as iFR<0.90) after a PCI that appeared to be successful based on angiography.	end of procedure/intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Events	Composite endpoint of cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization or recurrent ischemia at one year after PCI	12 months
Target Vessel Failure	Target vessel failure defined as cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization	12 months
Quality of Life Change From Baseline to 12 Months Follow-up	Quality of life (assessed by the Seattle Angina Questionnaire) at baseline, 30-days, 6 months and 1 year (12 months). Minimum score is 0 and maximum score is 100, with a high score representing a more positive quality of life score. Outcome is the change in score from baseline to 12 months follow-up.	12 months
Cardiac Mortality	All-cause and cardiac mortality at one year	12 months
Target Vessel MI	Target vessel Myocardial infarction at one year	12 month
Target Vessel Revascularization	Ischemia-driven target vessel revascularization at one year	12 month
Recurrent Ischemia	Recurrent ischemia at one-year	12 month
Correlation Between iFR and Angiographic Visual Interpretation	Correlation between iFR <0.90 and coronary stenosis >50% assessed by visual interpretation. This was tested using generalized estimating equations for logistic regression to account for the correlation of observations from the same subject. An absolute value of exactly 1 implies that a linear equation describes the relationship between iFR and visual interpretation of the angiography. Outcome reports how well the iFR value and the visual interpretation are in agreement (for example, when iFR <0.90 and coronary stenosis >50% assessed by visual interpretation the correlation is 1).	at the end of the procedure/intervention
Number of Participants in Which the iFR Would Become Non-significant if a Focal Stenosis Demonstrated by iFR Pullback Were Treated With PCI	Number of participants in which the iFR would become non-significant if a focal stenosis demonstrated by iFR pullback were treated with PCI	Procedural
Differentiation	Differentiation of the cause for impaired iFR	End of procedure /intervention
Delta iFR	Predictors of delta iFR before and after PCI, or predictors of impaired iFR Outcome is presented as the odds ratio (OR) that the post-PCI iFR will be <0.90. An OR > 1 means greater odds that the post-PCI iFR is <0.90, OR = 1 means there is no association, and OR < 1 means there is a lower odds that the post-PCI iFR is <0.90.	at the end of the procedure/intervention

Collaborators and Investigators

• Sponsor: Volcano Corporation
• Collaborators: Duke Clinical Research Institute; Cardiovascular Research Foundation, New York
• Investigators: Study Director: Becky Inderbitzen, MSE, Philips (Volcano)

Publications and helpful links

General Publications

• Jeremias A, Davies JE, Maehara A, Matsumura M, Schneider J, Tang K, Talwar S, Marques K, Shammas NW, Gruberg L, Seto A, Samady H, Sharp A, Ali ZA, Mintz G, Patel M, Stone GW. Blinded Physiological Assessment of Residual Ischemia After Successful Angiographic Percutaneous Coronary Intervention: The DEFINE PCI Study. JACC Cardiovasc Interv. 2019 Oct 28;12(20):1991-2001. doi: 10.1016/j.jcin.2019.05.054.
• Patel MR, Jeremias A, Maehara A, Matsumura M, Zhang Z, Schneider J, Tang K, Talwar S, Marques K, Shammas NW, Gruberg L, Seto A, Samady H, Sharp ASP, Ali ZA, Mintz G, Davies J, Stone GW. 1-Year Outcomes of Blinded Physiological Assessment of Residual Ischemia After Successful PCI: DEFINE PCI Trial. JACC Cardiovasc Interv. 2022 Jan 10;15(1):52-61. doi: 10.1016/j.jcin.2021.09.042.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2017
• Primary Completion (Actual): January 18, 2019
• Study Completion (Actual): February 18, 2020

Study Registration Dates

• First Submitted: March 13, 2017
• First Submitted That Met QC Criteria: March 13, 2017
• First Posted (Actual): March 20, 2017

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: February 21, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Pathological Conditions, Anatomical; Coronary Disease; Chest Pain; Coronary Artery Disease; Constriction, Pathologic; Angina Pectoris; Angina, Stable; Angina, Unstable; Coronary Stenosis
• Other Study ID Numbers: 160101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No