LRP: The Lipid-Rich Plaque Study

• Sponsor: Infraredx (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02033694
• Collaborator: Medstar Health Research Institute (Other)
• Enrollment: 1,563
• Locations: 41
• Actual Duration (Months): 55
• Patients Per Site: 38.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to enhance medical knowledge of the causes of future coronary problems. Many studies in patients who have already experienced a coronary problem point to the danger associated with plaques that are rich in cholesterol. This study determines if the near-infrared method of detection of these fatty plaques can predict future events. If dangerous plaques can be identified, there are many treatments already available that could be tested for their ability to prevent coronary events.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease; Atherosclerosis	Device: NIRS-IVUS Imaging (TVC Imaging System)

Study Design

• Study Type: Observational
• Actual Enrollment: 1563 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: The Lipid-Rich Plaque (LRP) Study
• Actual Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Participants With 2 Years Follow up Participants with NIRS-IVUS imaging at baseline and assigned to follow up for Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) for 2 years	Device: NIRS-IVUS Imaging (TVC Imaging System); Diagnostic Imaging Catheter

Outcome Measures

Primary Outcome Measures

1. Number of Participants Stratified as Non-Index Culprit Lesion Related Major Adverse Cardiac Events (NC-MACE) or No NC-MACE and Association With maxLCBI4mm as a Continuous Variable [2 years]

   Association of maximum 4 mm Lipid Core Burden Index (maxLCBI4mm) as a continuous value in 100 unit increments in all imaged arteries and NC-MACE at both (1) Patient Level and (2) Plaque Level Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) is defined as a composite of: cardiac death cardiac arrest non-fatal myocardial infarction (MI) acute coronary syndrome revascularization by coronary artery bypass graft (CABG) or percutaneous intervention (PCI) rehospitalization for progressive angina, related to a non-index culprit lesion

Secondary Outcome Measures

1. Number of Participants Stratified as NC-MACE or No NC-MACE and Association With maxLCBI4mm More Than a Threshold of 400 [2 years]

   Association of maxLCBI4mm more than and less than a threshold of 400 in all imaged arteries and NC-MACE at both (1) Patient Level and (2) Plaque Level Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) is defined as a composite of: cardiac death cardiac arrest non-fatal myocardial infarction (MI) acute coronary syndrome revascularization by coronary artery bypass graft (CABG) or percutaneous intervention (PCI) rehospitalization for progressive angina, related to a non-index culprit lesion

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

General Inclusion Criteria:

• Subjects presenting for coronary angiography in whom IVUS imaging is likely to be performed for clinical purposes.

• Greater than 18 years of age.

• Clinical presenting symptoms meeting one of the three criteria below:

1. Subjects presenting with an acute coronary syndrome (ACS) including at least one of the following:

2. Elevated cardiac biomarkers with CK-MB or troponin greater than upper limits of normal;

3. ST depression or ST elevation >1mm in 2 or more contiguous leads in the absence of LVH, paced rhythm, BBB or early repolarization;

4. A stabilized patient 24 to 72 hours post STEMI;

5. Unstable angina pectoris;

6. Stable angina pectoris and/or a positive functional study with evidence of ischemia.

Angiographic Inclusion Criteria

• At least one Suspected Index Culprit Lesion requiring imaging with IVUS and/or NIRS for clinical indications.

• At least two native epicardial coronary arteries (which may include the Suspected Index Culprit Artery) eligible for imaging with NIRS-IVUS.

IVUS/NIRS Imaging Inclusion Criterion

• A minimum of a total 50 mm of coronary artery not involved in a prior or Index Procedure PCI (including the 5mm borders on either edge of the site receiving PCI) must be scanned. This 50mm total length may include contributions from the Suspected Index Culprit Arteries and from Index Non-Culprit Arteries. This total length must include contributions from two or more native imaged arteries.

Exclusion Criteria:

• Unstable patients (STEMI within the prior 24 hours; cardiogenic shock, hypotension needing inotropes, hypoxia needing intubation, and IABP) and patients that had a procedural complication (coronary dissection, perforation or a complication that would necessitate immediate-unplanned revascularization) during index PCI procedure.

• History of CABG or planned CABG within 6 months following NIRS-IVUS imaging.

• Patient has additional lesion(s) that needs a staged PCI.

• Subject life expectancy is less than 2 years at time of index catheterization.

• Subject with ejection fraction (EF) <30%.

• Subject pacemaker dependent/paced rhythm.

• Subject pregnant and lactating.

• Any other factor that the investigator feels would put the patient at increased risk or otherwise make the patient unsuitable for participation in the protocol

• Patients undergoing performance of PCI in all three major vessels during the index PCI.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Los Angeles Medical Center	Los Angeles	California	United States
2	Washington Hospital Center	Washington	District of Columbia	United States
3	JFK Medical Center	Atlantis	Florida	United States
4	Delray Medical Center	Delray Beach	Florida	United States
5	Palmetto General Hospital	Hialeah	Florida	United States
6	Florida Hospital Orlando	Orlando	Florida	United States
7	Palm Beach Gardens Medical Center	Palm Beach Gardens	Florida	United States
8	Memorial Hospital West	Pembroke Pines	Florida	United States
9	Emory Midtwon	Atlanta	Georgia	United States
10	Emory University	Atlanta	Georgia	United States
11	Alexian Brothers Heart and Vascular Institute	Elk Grove Village	Illinois	United States
12	St. John's Springfield	Springfield	Illinois	United States
13	Community Heart & Vascular	Indianapolis	Indiana	United States
14	Methodist	Merrillville	Indiana	United States
15	Central Baptist Hospital	Lexington	Kentucky	United States
16	McLaren Bay Region	Bay City	Michigan	United States
17	St. John's	Detroit	Michigan	United States
18	McLaren-Macomb	Mount Clemens	Michigan	United States
19	Crittenton Hospital	Rochester	Michigan	United States
20	University of Minnesota Medical Center	Minneapolis	Minnesota	United States
21	Columbia University	New York	New York	United States
22	LIJ Health System	New York	New York	United States
23	New York Presbyterian Hospital Cornell	New York	New York	United States
24	Metrohealth	Cleveland	Ohio	United States
25	Hillcrest Oklahoma Heart Institute	Tulsa	Oklahoma	United States
26	Medical University of South Carolina	Charleston	South Carolina	United States
27	University of Texas Medical Branch	Galveston	Texas	United States
28	St. Luke's Episcopal Hospital	Houston	Texas	United States
29	Heart Hospital Plano	Plano	Texas	United States
30	Davis Hospital and Medical Center	Layton	Utah	United States
31	Charleston Area Medical Center	Charleston	West Virginia	United States
32	San Biovanni Hospital	Rome		Italy
33	Latvian Centre of Cardiology	Riga		Latvia
34	Academic Medical Center	Amsterdam		Netherlands
35	Radboud University Medical Centre	Nijmegen		Netherlands
36	Erasmus Medical Centre	Rotterdam		Netherlands
37	Maasstad Ziekenhuis	Rotterdam		Netherlands
38	SUSCCH, a.s.	Banska Bystrica		Slovakia
39	Golden Jubilee National Hospital	Clydebank		United Kingdom
40	University of Edinburgh	Edinburgh		United Kingdom
41	Royal Brompton Hospital	London		United Kingdom

Sponsors and Collaborators

• Infraredx
• Medstar Health Research Institute

Investigators

• Principal Investigator: Ron Waksman, MD, MedStar Heart Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 26, 2013

More Information

Additional Information:

• The Lipid-Rich Plaque Study of vulnerable plaques and vulnerable patients: Study design and rationale. Am Heart J. 2017
• Identification of patients and plaques vulnerable to future coronary events with near-infrared spectroscopy intravascular ultrasound imaging: a prospective, cohort study. Lancet. 2019

Publications

• Waksman R, Di Mario C, Torguson R, Ali ZA, Singh V, Skinner WH, Artis AK, Cate TT, Powers E, Kim C, Regar E, Wong SC, Lewis S, Wykrzykowska J, Dube S, Kazziha S, van der Ent M, Shah P, Craig PE, Zou Q, Kolm P, Brewer HB, Garcia-Garcia HM; LRP Investigators. Identification of patients and plaques vulnerable to future coronary events with near-infrared spectroscopy intravascular ultrasound imaging: a prospective, cohort study. Lancet. 2019 Nov 2;394(10209):1629-1637. doi: 10.1016/S0140-6736(19)31794-5. Epub 2019 Sep 27. Erratum in: Lancet. 2019 Nov 2;394(10209):1618.
• Waksman R, Torguson R, Spad MA, Garcia-Garcia H, Ware J, Wang R, Madden S, Shah P, Muller J. The Lipid-Rich Plaque Study of vulnerable plaques and vulnerable patients: Study design and rationale. Am Heart J. 2017 Oct;192:98-104. doi: 10.1016/j.ahj.2017.02.010. Epub 2017 Feb 16. Review.

• Responsible Party: Infraredx
• ClinicalTrials.gov Identifier: NCT02033694
• Other Study ID Numbers: The LRP Study
• First Posted: Jan 13, 2014
• Last Update Posted: May 19, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Infraredx: Lipid; Vulnerable Plaque; Plaque; Cholesterol; Near Infrared Spectroscopy; NIRS-IVUS; Intravascular Ultrasound; Angiography; Coronary Imaging
• Additional relevant MeSH terms: Coronary Artery Disease; Atherosclerosis

Study Results

Participant Flow

Recruitment Details	Enrolled patients with a large LRP (Maximum Lipid Core Burden Index>250 in 4 mm or maxLCBI4mm>=250) were assigned to 2 year follow up to determine if a new coronary event had occurred. A randomly selected half of the patients with a small or no LRP (MaxLCBI4mm<250) had 2 year follow up.
Pre-assignment Detail	A randomly selected half of the patients with a small or no LRP (MaxLCBI4mm<250) did not have 2 year follow up and were not included in the primary analyses. This reduced the total number of patients followed for two years to 1271 patients.

Arm/Group Title	Participants With 2 Year Follow up
Arm/Group Description	Participants with NIRS-IVUS imaging at baseline and assigned to follow up for Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) for 2 years
Period Title: Overall Study
STARTED	1271
COMPLETED	1271
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Participants With 2 Year Follow up
Arm/Group Description	Participants with NIRS-IVUS imaging at baseline and assigned to follow up for Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) for 2 years
Overall Participants	1271
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (10.3)
Sex: Female, Male (Count of Participants)
Female	388 30.5%
Male	883 69.5%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	942 74.1%
African American	158 12.4%
Asian Pacific	44 3.5%
Native American	0 0%
Other	128 10.1%
Hispanic	101 7.9%
Region of Enrollment (Count of Participants)
Netherlands	187 14.7%
Latvia	10 0.8%
United States	1001 78.8%
United Kingdom	46 3.6%
Italy	10 0.8%
Slovakia	17 1.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Stratified as Non-Index Culprit Lesion Related Major Adverse Cardiac Events (NC-MACE) or No NC-MACE and Association With maxLCBI4mm as a Continuous Variable
Description	Association of maximum 4 mm Lipid Core Burden Index (maxLCBI4mm) as a continuous value in 100 unit increments in all imaged arteries and NC-MACE at both (1) Patient Level and (2) Plaque Level Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) is defined as a composite of: cardiac death cardiac arrest non-fatal myocardial infarction (MI) acute coronary syndrome revascularization by coronary artery bypass graft (CABG) or percutaneous intervention (PCI) rehospitalization for progressive angina, related to a non-index culprit lesion
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Patients assigned to 2 year follow up were analyzed, at the patient and plaque level, to test the association between maximum 4 mm Lipid Core Burden Index (maxLCBI4mm) and Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE).

Arm/Group Title	Participants With 2 Year Follow up
Arm/Group Description	Participants with NIRS-IVUS imaging at baseline and assigned to follow up for Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) for 2 years
Measure Participants	1271
Participants with NC-MACE	104 8.2%
Participants with No NC-MACE	1167 91.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With 2 Year Follow up
	Comments	Hypothesis 1 (Vulnerable Patient Hypothesis) first fit a univariate proportional hazards regression model in which maxLCBI4mm is the only independent variable and NC-MACE during 2 years is the outcome. The null hypothesis tested by the Wald test that the regression coefficient in a proportional hazards regression model is significantly different from 0. This analysis determined whether maxLCBI4mmI is a risk factor for NC-MACE.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 1.09 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants With 2 Year Follow up
	Comments	Hypothesis 2 (Vulnerable Plaque Hypothesis) first fit a univariate proportional hazards regression model in which maxLCBI4mm in the coronary artery segment is the measure of exposure and NC-MACE during 2 years caused by a new culprit lesion in that segment is the outcome. This analysis was performed with adjustment for the potential clustering effect within patient utilizing the Wei, Lin and Weissfeld (WLW) methodology. This analysis determined whether maxLCBI4mm is a risk factor NC-MACE.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 1.30 to 1.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants Stratified as NC-MACE or No NC-MACE and Association With maxLCBI4mm More Than a Threshold of 400
Description	Association of maxLCBI4mm more than and less than a threshold of 400 in all imaged arteries and NC-MACE at both (1) Patient Level and (2) Plaque Level Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) is defined as a composite of: cardiac death cardiac arrest non-fatal myocardial infarction (MI) acute coronary syndrome revascularization by coronary artery bypass graft (CABG) or percutaneous intervention (PCI) rehospitalization for progressive angina, related to a non-index culprit lesion
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Patients assigned to 2 year follow up were analyzed, at the patient and plaque level to test the association between maximum 4mm Lipid Core Burden index (maxLCBI4mm) >400 and Non-Index Culprit Lesion related Major Cardiac Events (NC-MACE)

Arm/Group Title	Participants With 2 Year Follow up
Arm/Group Description	Participants with NIRS-IVUS imaging at baseline and follow up for 2 years
Measure Participants	1271
Participants with NC-MACE	104 8.2%
Participants with No NC-MACE	1167 91.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With 2 Year Follow up
	Comments	Secondary Hypothesis 1 (Vulnerable Patient)- Cox proportional hazards regression model to assess a threshold of maxLCBI4mm > 400 as the independent variable and NC-MACE during 2 years as the outcome.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	2.18
	Confidence Interval	(2-Sided) 95%; 1.48 to 3.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants With 2 Year Follow up
	Comments	Secondary Hypothesis 2 (Vulnerable Plaque)- Cox proportional hazards regression model to assess a threshold of maxLCBI4mm > 400 in the coronary artery segment as the independent variable and NC-MACE during 2 years caused by a new culprit lesion in that segment is the outcome.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	4.22
	Confidence Interval	(2-Sided) 95%; 2.39 to 7.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	The device has been approved as safe for imaging of coronary arteries by the FDA. Experience in greater than 5,000 patients has shown that the device safety profile does not differ from that of a conventional IVUS catheter. Serious adverse events associated with the device in the additional, non-culprit vessels were collected because this was the additional requirement for the study outside of routine medical care.
Arm/Group Title	All Patients With Baseline NIRS-IVUS Imaging
Arm/Group Description	Participants with NIRS-IVUS imaging at baseline
All Cause Mortality
	All Patients With Baseline NIRS-IVUS Imaging
	Affected / at Risk (%)	# Events
Total	0/1563 (0%)
Serious Adverse Events
	All Patients With Baseline NIRS-IVUS Imaging
	Affected / at Risk (%)	# Events
Total	6/1563 (0.4%)
Cardiac disorders
Dissection	4/1563 (0.3%)	4
Bradycardia	1/1563 (0.1%)	1
Thrombus with Chest Pain	1/1563 (0.1%)	1
Other (Not Including Serious) Adverse Events
	All Patients With Baseline NIRS-IVUS Imaging
	Affected / at Risk (%)	# Events
Total	0/1563 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.