DEFINE PCI: Physiologic Assessment of Coronary Stenosis Following PCI

• Sponsor: Volcano Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03084367
• Collaborator: Duke Clinical Research Institute (Other), Cardiovascular Research Foundation, New York (Other)
• Enrollment: 500
• Locations: 28
• Actual Duration (Months): 32
• Patients Per Site: 17.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease; Coronary Stenosis; Angina, Unstable; Angina, Stable	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 Design

• Study Type: Observational
• Actual Enrollment: 500 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: DEFINE PCI: Physiologic Assessment of Coronary Stenosis Following PCI
• Actual Study Start Date: Jun 20, 2017
• Actual Primary Completion Date: Jan 18, 2019
• Actual Study Completion Date: Feb 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
iFR post angiographically successful PCI	Diagnostic Test: iFR pullback; iFR pullback assessment post angiographically successful PCI

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Residual Ischemia (iFR <0.90) [end of procedure/intervention]

   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.

Secondary Outcome Measures

1. Cardiac Events [12 months]

   Composite endpoint of cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization or recurrent ischemia at one year after PCI

2. Target Vessel Failure [12 months]

   Target vessel failure defined as cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization

3. Quality of Life Change From Baseline to 12 Months Follow-up [12 months]

   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.

4. Cardiac Mortality [12 months]

   All-cause and cardiac mortality at one year

5. Target Vessel MI [12 month]

   Target vessel Myocardial infarction at one year

6. Target Vessel Revascularization [12 month]

   Ischemia-driven target vessel revascularization at one year

7. Recurrent Ischemia [12 month]

   Recurrent ischemia at one-year

8. Correlation Between iFR and Angiographic Visual Interpretation [at the end of the procedure/intervention]

   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).

9. Number of Participants in Which the iFR Would Become Non-significant if a Focal Stenosis Demonstrated by iFR Pullback Were Treated With PCI [Procedural]

   Number of participants in which the iFR would become non-significant if a focal stenosis demonstrated by iFR pullback were treated with PCI

10. Differentiation [End of procedure /intervention]

    Differentiation of the cause for impaired iFR

11. Delta iFR [at the end of the procedure/intervention]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Medical Center	Long Beach	California	United States	90822
2	Colorado Heart and Vascular	Lakewood	Colorado	United States	80204
3	Emory University Hospital	Atlanta	Georgia	United States	30322
4	Atlanta VA Medical Center	Decatur	Georgia	United States	30033
5	Rockford CV Associates	Rockford	Illinois	United States	61107
6	Midwest Cardiovascular Research Foundation	Davenport	Iowa	United States	52803
7	Baystate Medical Center	Springfield	Massachusetts	United States	01199
8	Minneapolis Heart Institute	Minneapolis	Minnesota	United States	55407
9	Dartmouth Hitchcock	Lebanon	New Hampshire	United States	03756
10	South Side Hospital	Bay Shore	New York	United States	11706
11	Northshore Hospital	Manhasset	New York	United States	11030
12	Columbia University Medical Center/NewYork Presbyterian Hospital	New York	New York	United States	10032
13	New York Presbyterian Hospital -Weill Cornell	New York	New York	United States	10065
14	Lenox Hill Hospital	New York	New York	United States	10075
15	St Francis Hospital	Roslyn	New York	United States	11576
16	SUNY- Stony Brook	Stony Brook	New York	United States	11794
17	Duke University Hospital	Durham	North Carolina	United States	27710
18	Vidant Medical Center	Greenville	North Carolina	United States	27835
19	Miriam Hospital	Providence	Rhode Island	United States	02906
20	Wellmont CVA Heart Insitute	Kingsport	Tennessee	United States	37660
21	VA North Texas Health Care	Dallas	Texas	United States	75216
22	Aurora St Lukes Medical Center	Milwaukee	Wisconsin	United States	53215
23	AMC Amsterdam	Amsterdam		Netherlands
24	VU University Medical Center	Amsterdam		Netherlands
25	Basildon Univeristy Hospital	Basildon		United Kingdom	SS165NL
26	Royal Bournemouth hospital	Bournemouth		United Kingdom	BH7 7DW
27	Royal Devon & Exeter NHS Foundation Trust	Exeter		United Kingdom	EX25DW
28	Imperial College of London- Hammersmith Hospital	London		United Kingdom	W12OHS

Sponsors and Collaborators

• Volcano Corporation
• Duke Clinical Research Institute
• Cardiovascular Research Foundation, New York

Investigators

• Study Director: Becky Inderbitzen, MSE, Philips (Volcano)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 26, 2017

More Information

Publications

None provided.

• Responsible Party: Volcano Corporation
• ClinicalTrials.gov Identifier: NCT03084367
• Other Study ID Numbers: 160101
• First Posted: Mar 20, 2017
• Last Update Posted: May 10, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Coronary Artery Disease; Angina Pectoris; Coronary Stenosis; Angina, Unstable; Angina, Stable; Constriction, Pathologic

Study Results

Participant Flow

Arm/Group Title	All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI
Arm/Group Description	all participants in the study with analyzable iFR pullback assessment that was performed after a successful PCI, where a successful PCI is assessed based on angiographic results.
Period Title: Overall Study
STARTED	500
Analyzable iFR Pullback Assessment Post Angiographically Successful PCI	467
COMPLETED	463
NOT COMPLETED	37

Baseline Characteristics

Arm/Group Title	Diagnostic Test: iFR Pullback
Arm/Group Description	iFR (instantaneous wave free ratio) pullback assessment post angiographically successful PCI
Overall Participants	500
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.4 (9.9)
Sex: Female, Male (Count of Participants)
Female	121 24.2%
Male	379 75.8%
Race and Ethnicity Not Collected (Count of Participants)
BMI (Body Mass Index) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.8 (8.8)
Smoker (Count of Participants)
Count of Participants [Participants]	83 16.6%
Diabetes Mellitus (Count of Participants)
Count of Participants [Participants]	169 33.8%
Insulin treated diabetes (Count of Participants)
Count of Participants [Participants]	48 9.6%
Hyperlipidemia (Count of Participants)
Count of Participants [Participants]	351 70.2%
Hypertension (Count of Participants)
Count of Participants [Participants]	383 76.6%
Renal disease (Count of Participants)
Count of Participants [Participants]	39 7.8%
Prior Percutaneous Coronary Intervention (PCI) (Count of Participants)
Count of Participants [Participants]	227 45.4%
Prior Myocardial Infarction (Count of Participants)
Count of Participants [Participants]	134 26.8%
Left ventricular ejection fraction (%) (% of blood ejected with each contraction) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% of blood ejected with each contraction]	56.3 (9)
Stable angina (Count of Participants)
Count of Participants [Participants]	212 42.4%
Unstable Angina (Count of Participants)
Count of Participants [Participants]	155 31%
NSTEMI (Non-ST Elevated Myocardial Infarction) (Count of Participants)
Count of Participants [Participants]	85 17%
Silent Ischemia (Count of Participants)
Count of Participants [Participants]	27 5.4%
Recent STEMI (ST Elevated MI) (>7days) (Count of Participants)
Count of Participants [Participants]	21 4.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Residual Ischemia (iFR <0.90)
Description	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.
Time Frame	end of procedure/intervention

Outcome Measure Data

Analysis Population Description

Total vessels/units (535) in participant population (467)

Arm/Group Title	All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI
Arm/Group Description	all participants in the study with analyzable iFR pullback assessment that was performed after a successful PCI, where a successful PCI is assessed based on angiographic results.
Measure Participants	467
Measure Number of vessels in 467 participants	535
Number [participants]	112 22.4%

2. Secondary Outcome

Title	Cardiac Events
Description	Composite endpoint of cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization or recurrent ischemia at one year after PCI
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The total number of participants was divided in two groups based on their post-PCI iFR result. (see primary endpoint) The total number of participants still in study at one year is 467.

Arm/Group Title	iFR >= 0.90	iFR < 0.90
Arm/Group Description	Participants with iFR >= 0.90 post-procedure	Participants with iFR < 0.90 post-procedure
Measure Participants	355	112
Count of Participants [Participants]	9 1.8%	3 NaN

3. Secondary Outcome

Title	Target Vessel Failure
Description	Target vessel failure defined as cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The total number of participants was divided in two groups based on their post-PCI iFR result. (see primary endpoint) The total number of participants still in study at one year is 467.

Arm/Group Title	iFR >= 0.90	iFR < 0.90
Arm/Group Description	Participants with iFR >= 0.90 post-procedure	Participants with iFR < 0.90 post-procedure
Measure Participants	355	112
Count of Participants [Participants]	4 0.8%	2 NaN

4. Secondary Outcome

Title	Quality of Life Change From Baseline to 12 Months Follow-up
Description	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.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	iFR <= 0.94	iFR > 0.94
Arm/Group Description	post-procedural iFR <= 0.94	post-procedural iFR > 0.94
Measure Participants	246	150
Mean (Standard Deviation) [units on a scale]	21.42 (24.99)	20.73 (21.83)

5. Secondary Outcome

Title	Cardiac Mortality
Description	All-cause and cardiac mortality at one year
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	iFR >= 0.90	iFR < 0.90
Arm/Group Description	Participants with iFR >= 0.90 post-procedure	Participants with iFR < 0.90 post-procedure
Measure Participants	355	112
Count of Participants [Participants]	0 0%	0 NaN

6. Secondary Outcome

Title	Target Vessel MI
Description	Target vessel Myocardial infarction at one year
Time Frame	12 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	iFR >= 0.90	iFR < 0.90
Arm/Group Description	Participants with iFR >= 0.90 post-procedure	Participants with iFR < 0.90 post-procedure
Measure Participants	355	112
Count of Participants [Participants]	4 0.8%	2 NaN

7. Secondary Outcome

Title	Target Vessel Revascularization
Description	Ischemia-driven target vessel revascularization at one year
Time Frame	12 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	iFR >= 0.90	iFR < 0.90
Arm/Group Description	Participants with iFR >= 0.90 post-procedure	Participants with iFR < 0.90 post-procedure
Measure Participants	355	112
Count of Participants [Participants]	10 2%	3 NaN

8. Secondary Outcome

Title	Recurrent Ischemia
Description	Recurrent ischemia at one-year
Time Frame	12 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	iFR >= 0.90	iFR < 0.90
Arm/Group Description	Participants with iFR >= 0.90 post-procedure	Participants with iFR < 0.90 post-procedure
Measure Participants	355	112
Count of Participants [Participants]	6 1.2%	1 NaN

9. Secondary Outcome

Title	Correlation Between iFR and Angiographic Visual Interpretation
Description	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).
Time Frame	at the end of the procedure/intervention

Outcome Measure Data

Analysis Population Description

The correlation calculation was performed on the total number of analyzable participants with a post-PCI iFR pullback assessment.

Arm/Group Title	All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI
Arm/Group Description	all participants in the study with analyzable iFR pullback assessment that was performed after a successful PCI, where a successful PCI is assessed based on angiographic results.
Measure Participants	467
Number [coefficient of determination (R2)]	0.03

10. Secondary Outcome

Title	Number of Participants in Which the iFR Would Become Non-significant if a Focal Stenosis Demonstrated by iFR Pullback Were Treated With PCI
Description	Number of participants in which the iFR would become non-significant if a focal stenosis demonstrated by iFR pullback were treated with PCI
Time Frame	Procedural

Outcome Measure Data

Analysis Population Description

This analysis assumes that all focal lesions with post-PCI iFR <0.90 were successfully treated with additional PCI. Using the cutoff of iFR <0.90, the outcome is the number of participants that would remain, or not have been treated, because the iFR measurements are under 0.90.

Arm/Group Title	All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI
Arm/Group Description	all participants in the study with analyzable iFR pullback assessment that was performed after a successful PCI, where a successful PCI is assessed based on angiographic results.
Measure Participants	467
Count of Participants [Participants]	23 4.6%

11. Secondary Outcome

Title	Differentiation
Description	Differentiation of the cause for impaired iFR
Time Frame	End of procedure /intervention

Outcome Measure Data

Analysis Population Description

Number of vessels in which residual ischemia (post-PCI iFR <0.90) after angiographically successful PCI

Arm/Group Title	Residual Ischemia (Post-PCI iFR <0.90) After Angiographically Successful PCI
Arm/Group Description	Residual ischemia (post-PCI iFR <0.90)
Measure Participants	112
Measure vessels	114
single or multiple residual focal lesions	93
diffuse disease	21

12. Secondary Outcome

Title	Delta iFR
Description	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.
Time Frame	at the end of the procedure/intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI
Arm/Group Description	all participants in the study with analyzable iFR pullback assessment that was performed after a successful PCI, where a successful PCI is assessed based on angiographic results.
Measure Participants	467
pre-PCI reference vessel diameter	0.32
lesion location in left anterior descending coronary artery	5.65

Adverse Events

Time Frame	Adverse Device Effects, Serious Adverse Device Effects, and Unanticipated Adverse Device Effects were collected and if any occurred, they would likely occur during the procedure when the device is being used. Subjects were followed for 12 months and all complaints promptly reported.
Adverse Event Reporting Description	As noted above, the only reportable events were Adverse Device Effects, Serious Adverse Device Effects, and Unanticipated Adverse Device Effects. Subjects were followed for 12 months, with follow-up visits at 1, 6, and 12 months.
Arm/Group Title	All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI
Arm/Group Description	all participants in the study with analyzable iFR pullback assessment that was performed after a successful PCI, where a successful PCI is assessed based on angiographic results.
All Cause Mortality
	All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI
	Affected / at Risk (%)	# Events
Total	0/467 (0%)
Serious Adverse Events
	All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI
	Affected / at Risk (%)	# Events
Total	12/467 (2.6%)
Cardiac disorders
Target Vessel Myocardial Infarction	6/467 (1.3%)	6
Ischemia-driven Target Vessel Revascularization	0/467 (0%)	0
Recurrent Ischemia	7/467 (1.5%)	7
Cardiac Death	0/467 (0%)	0
Other (Not Including Serious) Adverse Events
	All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI
	Affected / at Risk (%)	# Events
Total	0/467 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.