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Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI

Primary Purpose

Myocardial Ischemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Regadenoson
gadofoveset trisodium
Sponsored by
Northwestern University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Myocardial Ischemia focused on measuring Magnetic Resonance Imaging, regadenoson

Eligibility Criteria

19 Years - 89 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

10) 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

Sites / Locations

  • Northwestern University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

coronary artery disease patients

Arm 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.

Outcomes

Primary Outcome Measures

Quantification of Myocardial Blood Volume
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.

Secondary Outcome Measures

Full Information

First Posted
July 30, 2012
Last Updated
August 16, 2019
Sponsor
Northwestern University
Collaborators
Astellas Pharma Global Development, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01655043
Brief Title
Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI
Official Title
Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwestern University
Collaborators
Astellas Pharma Global Development, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Ischemia
Keywords
Magnetic Resonance Imaging, regadenoson

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
Single
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
coronary artery disease patients
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Regadenoson
Other Intervention Name(s)
Lexiscan
Intervention Description
Regadenoson will be infused intravenously 0.4 mg/5 mL (0.08 mg/mL) as a single bolus.
Intervention Type
Drug
Intervention Name(s)
gadofoveset trisodium
Other Intervention Name(s)
Ablavar
Intervention Description
All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar) at both stress and rest.
Primary Outcome Measure Information:
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Age 18 to 89 years; Known contraindication to MR imaging (such as pacemaker placement, magnetic implants, etc); Claustrophobia; Inability to perform an adequate breath-hold for imaging, Inability to provide informed consent; 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; Pregnant and lactating women; Patients with hypersensitivity to gadolinium contrast agents, metoprolol, adenosine, or nitroglycerin; 10) Contra indication for Regadenoson 2nd- or 3rd-degree AV block (except in patients with a functioning artificial pacemaker) Sinus node disease (except in patients with a functioning artificial pacemaker) Unstable angina Acute myocardial infarction Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma) Hypersensitivity to adenosine Caffeine within 12-24 hours Theophylline and Dipyridamole products within 24 hours
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James C Carr, MD
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17194875
Citation
Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69-171. doi: 10.1161/CIRCULATIONAHA.106.179918. Epub 2006 Dec 28. No abstract available. Erratum In: Circulation. 2007 Feb 6;115(5):e172. Circulation. 2010 Jul 6;122(1):e9. Kissela, Bret [corrected to Kissela, Brett].
Results Reference
result
PubMed Identifier
16353442
Citation
Elkington AG, Gatehouse PD, Ablitt NA, Yang GZ, Firmin DN, Pennell DJ. Interstudy reproducibility of quantitative perfusion cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2005;7(5):815-22. doi: 10.1080/10976640500287877.
Results Reference
result
PubMed Identifier
9498540
Citation
Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA, Schulman SP, Blumenthal RS, Lima JA. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation. 1998 Mar 3;97(8):765-72. doi: 10.1161/01.cir.97.8.765.
Results Reference
result

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Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI

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