Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI

NCT01655043 | Completed Phase 2 Results DMC

• 2 other identifiers: STU00050900000598
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Myocardial Ischemia

Keywords

Magnetic Resonance Imaging; regadenoson

Outcome Measures

Primary Outcomes (1)

• 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.

  outcome measured following single MRI scan

Study Arms (1)

coronary artery disease patients

EXPERIMENTAL

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; Drug: gadofoveset trisodium

Interventions

Regadenoson DRUG

Regadenoson will be infused intravenously 0.4 mg/5 mL (0.08 mg/mL) as a single bolus.

Also known as: Lexiscan

coronary artery disease patients

gadofoveset trisodium DRUG

All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar) at both stress and rest.

Also known as: Ablavar

coronary artery disease patients

Eligibility Criteria

• Age: 19 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• \) Contra indication for Regadenoson
• nd- 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

Sponsors & Collaborators

• Northwestern University: lead
• Astellas Pharma Global Development, Inc.: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (3)

• 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.

  PMID: 17194875 RESULT

• 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.

  PMID: 16353442 RESULT

• 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.

  PMID: 9498540 RESULT

MeSH Terms

Conditions

Myocardial Ischemia

Interventions

regadenoson

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Limitations and 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

Results Point of Contact

• Title: Dr. James Carr
• Organization: Northwestern University

jcarr@northwestern.edu

(312)926-2270

Study Officials

• James C Carr, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: SINGLE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: director of cardiovascular imaging

Study Record Dates

• First Submitted: July 30, 2012
• First Posted: August 1, 2012
• Study Start: September 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: August 28, 2019
• Results First Posted: March 27, 2015

Record last verified: 2019-08

Locations

US (1)