Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01655043
• Collaborator: Astellas Pharma Global Development, Inc. (Industry)
• Enrollment: 20
• Location: 1
• Arm: 1
• Duration (Months): 17
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Coronary artery disease (CAD, coronary heart disease) is the leading cause of death in the U.S., causing 1 in 5 deaths in 2005. The current method for diagnosing coronary artery disease that is considered most accurate is coronary angiography however it involves risk and radiation. Alternatively nuclear imaging test and MRI stress test only permits the semi qualitative analysis of the myocardial perfusion images.

In this proposal the investigators will develop a means to calculate Coronary Flow Reserve (CFR) using the MRI. the investigators approach has the potential to reduce mortality from myocardial infarction by effecting a change in the patient management paradigm. Absolute quantification of myocardial perfusion will detect coronary stenosis and CAD in patients with more accuracy than the semi-quantitative or qualitative analysis of perfusion images. Measurement of Coronary Flow Reserve is important for the following reasons: decrease of coronary flow reserve has been identified as a first effect of CAD; it provides an objective measure of treatment efficacy.

The purpose of this study is to compare images from nuclear stress test and/or coronary angiography with Magnetic Resonance Imaging (MRI) that will evaluate subjects with coronary artery disease calculating myocardial blood flow using a novel MRI technique combined to an extracellular Gadolinium-based contrast agent and stressor agent

Condition or Disease	Intervention/Treatment	Phase
Myocardial Ischemia	Drug: Regadenoson; Drug: gadofoveset trisodium	Phase 2

Detailed Description

The main hypothesis the investigators will test is that changes in myocardial blood volume, under physiologic stress, correlate with myocardial flow reserve as measured in low spatial resolution nuclear SPECT scans. Secondary hypothesis is that stress perfusion as quantified with bolus height corrected gadofosveset trisodium images, better correlate with SPECT perfusion than uncorrected, relative perfusion values.

The investigators propose implementing the scan protocol using a 1.5T or 3.0T MRI scanner. The investigators will scan a series of 20 patients recruited from the nuclear stress lab at Northwestern Memorial Hospital. These subjects will be approached and enrolled into a HIPPA Compliant, IRB approved research study to assess the effectiveness of myocardial perfusion and blood volume images to measure myocardial blood volume. Subjects will be scanned with a modified version of the clinical stress-perfusion protocol. Correlation analysis will be used to test the hypothesis that quantitative blood volume is an indicator of myocardial flow reserve.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: Single
• Primary Purpose: Diagnostic
• Official Title: Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: coronary artery disease patients Patients with suspected coronary artery disease prospectively recruited for myocardial perfusion MRI. All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar, Lantheus) at both stress and rest. Stress to be induced using 5 ml intravenous (IV) regadenoson (Lexiscan, Astellas US LLC), and the effects of regadenoson were reversed with 50 mg IV aminophylline following the completion of stress imaging.

Drug: Regadenoson; Regadenoson will be infused intravenously 0.4 mg/5 mL (0.08 mg/mL) as a single bolus.; Other Names: Lexiscan ; Drug: gadofoveset trisodium; All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar) at both stress and rest.; Other Names: Ablavar

Outcome Measures

Primary Outcome Measures

1. Quantification of Myocardial Blood Volume [outcome measured following single MRI scan]

   The investigators anticipated that a novel MRI imaging protocol using a high relaxivity blood-pool contrast agent (gadofosveset trisodium) would be capable of quantifying coronary flow reserve based on quantification of myocardial blood volume and would be correlated with myocardial flow reserve as measured in low spatial resolution nuclear SPECT scans. Pre- and post- gadofosveset trisodium images were to be used to calculate the myocardial blood volume. Myocardial blood volume is derived from an equation of the relaxation times of hydrogen atoms in the blood and myocardium. If the agent administered did not behave as a true intravascular agent in the myocardium, quantification of myocardial intravascular blood volume (and hence a calculated coronary flow reserve) could not be calculated using the specified approach. In this case, relaxation times would be reported. Relaxation (R) times are measured in inverse seconds.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Under an Institutional Committee on Human Research board approved protocol, 20 patients with a suspected myocardial ischemic disease with positive stress nuclear medicine test laboratory will be recruited in this prospective study. All subjects will be screened for GFR within 24 hours before the exam. All patients must have a GFR > 30 mL/min/1.73m2 to be included in the study.

All subjects will be selected following the Nephrogenic Systemic Fibrosis (NSF) guidelines. All dialysis patients or end-stage renal disease patients with a creatinine clearance of < 30mL/min will not be selected for the study to avoid NSF.

Exclusion Criteria:

1. Age 18 to 89 years;

2. Known contraindication to MR imaging (such as pacemaker placement, magnetic implants, etc);

3. Claustrophobia;

4. Inability to perform an adequate breath-hold for imaging,

5. Inability to provide informed consent;

6. all subjects will be will be screened for GFR within 24 hours before the exam and subjects presenting with GFR < 60 ml/min will be excluded;

7. Pregnant and lactating women;

8. Patients with hypersensitivity to gadolinium contrast agents, metoprolol, adenosine, or nitroglycerin;

1. Contra indication for Regadenoson

1. 2nd- or 3rd-degree AV block (except in patients with a functioning artificial pacemaker)

2. Sinus node disease (except in patients with a functioning artificial pacemaker)

3. Unstable angina

4. Acute myocardial infarction

5. Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma)

6. Hypersensitivity to adenosine

7. Caffeine within 12-24 hours

8. Theophylline and Dipyridamole products within 24 hours

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University
• Astellas Pharma Global Development, Inc.

Investigators

• Principal Investigator: James C Carr, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: James Carr, director of cardiovascular imaging, Northwestern University
• ClinicalTrials.gov Identifier: NCT01655043
• Other Study ID Numbers: STU00050900; 000598
• First Posted: Aug 1, 2012
• Last Update Posted: Aug 28, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by James Carr, director of cardiovascular imaging, Northwestern University: Magnetic Resonance Imaging; regadenoson
• Additional relevant MeSH terms: Myocardial Ischemia; Ischemia; Regadenoson

Study Results

Participant Flow

Arm/Group Title	Coronary Artery Disease Patients
Arm/Group Description	Patients with suspected coronary artery disease prospectively recruited for myocardial perfusion MRI. All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar, Lantheus) at both stress and rest. Stress to be induced using 5 ml intravenous (IV) regadenoson (Lexiscan, Astellas US LLC), and the effects of regadenoson were reversed with 50 mg IV aminophylline following the completion of stress imaging.
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Coronary Artery Disease Patients
Arm/Group Description	Patients with suspected coronary artery disease prospectively recruited for myocardial perfusion MRI. All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar, Lantheus) at both stress and rest. Stress to be induced using 5 ml intravenous (IV) regadenoson (Lexiscan, Astellas US LLC), and the effects of regadenoson were reversed with 50 mg IV aminophylline following the completion of stress imaging.
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.8 (12.2)
Sex: Female, Male (Count of Participants)
Female	7 35%
Male	13 65%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5%
Not Hispanic or Latino	18 90%
Unknown or Not Reported	1 5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 10%
White	15 75%
More than one race	0 0%
Unknown or Not Reported	2 10%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Quantification of Myocardial Blood Volume
Description	The investigators anticipated that a novel MRI imaging protocol using a high relaxivity blood-pool contrast agent (gadofosveset trisodium) would be capable of quantifying coronary flow reserve based on quantification of myocardial blood volume and would be correlated with myocardial flow reserve as measured in low spatial resolution nuclear SPECT scans. Pre- and post- gadofosveset trisodium images were to be used to calculate the myocardial blood volume. Myocardial blood volume is derived from an equation of the relaxation times of hydrogen atoms in the blood and myocardium. If the agent administered did not behave as a true intravascular agent in the myocardium, quantification of myocardial intravascular blood volume (and hence a calculated coronary flow reserve) could not be calculated using the specified approach. In this case, relaxation times would be reported. Relaxation (R) times are measured in inverse seconds.
Time Frame	outcome measured following single MRI scan

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Coronary Artery Disease Patients
Arm/Group Description	Patients with suspected coronary artery disease prospectively recruited for myocardial perfusion MRI. All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar, Lantheus) at both stress and rest. Stress to be induced using 5 ml intravenous (IV) regadenoson (Lexiscan, Astellas US LLC), and the effects of regadenoson were reversed with 50 mg IV aminophylline following the completion of stress imaging.
Measure Participants	20
Delta R1(blood)	3.63 (.54)
Delta R1(myo)	1.23 (.24)

Adverse Events

Arm/Group Title	Coronary Artery Disease Patients
Arm/Group Description	Patients with suspected coronary artery disease prospectively recruited for myocardial perfusion MRI. All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar, Lantheus) at both stress and rest. Stress to be induced using 5 ml intravenous (IV) regadenoson (Lexiscan, Astellas US LLC), and the effects of regadenoson were reversed with 50 mg IV aminophylline following the completion of stress imaging.
All Cause Mortality
	Coronary Artery Disease Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Coronary Artery Disease Patients
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Other (Not Including Serious) Adverse Events
	Coronary Artery Disease Patients
	Affected / at Risk (%)	# Events
Total	0/20 (0%)

Limitations/Caveats

The small number of subjects results in reduced statistical power; The cohort was selected from patients at a single medical center, potentially reducing generalizability

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.