Efficacy of Dotarem® (Gd-DOTA) Versus Gadovist® (Gd-DO3A-butrol) for Late Gadolinium Enhancement Cardiac Magnetic Resonance

Efficacy of Dotarem® (Gd-DOTA) Versus Gadovist® (Gd-DO3A-butrol) for Late Gadolinium Enhancement Cardiac Magnetic Resonance and Relationship to Outcomes: A Pilot Study

This project is designed to demonstrate equivalence of Dotarem enhanced LGE-CMR (late gadolinium enhancement cardiac MRI) with Gadoviost enhanced LGE-CMR from the standpoint of visual image quality, quantitative image quality, and association with clinical outcomes.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Cardiomyopathy
• Intervention / Treatment: Drug: Cardiac MRI taken using contrast agent, Dotarem® (Gd-DOTA); Drug: Cardiac MRI with contrast agent, Gadovist

Detailed Description

Gadolinium-containing contrast agents (GdCAs) are intravenous agents used for contrast enhancement with magnetic resonance imaging (MRI) and with magnetic resonance angiography (MRA). The GdCAs (gadodiamide, gadopentetic acid, gadobenic acid, gadoxetic acid, gadoteridol, gadobutrol and gadoteric acid) have been in use for few decades for different types of MR scan varying from product to product, including liver, brain, and whole body scan.

Recently, there has been a great interest in employing contrast-related techniques to assess for fibrosis in the myocardium of the heart. As opposed to nuclear methods, viability assessment by MRI is a nonstress examination that provides high-resolution detail, including functional assessment of the left ventricle in approximately 30 minutes. Assessment of myocardial viability is performed using 5- to 20-minute delayed, gadolinium-enhanced MRI. On delayed MRI, there is a relatively decreased washout of the gadolinium contrast agent in areas of myocardium that have been replaced by fibrosis or scar. In normal viable myocardium, the gadolinium contrast agent washes out more rapidly than it does from the fibrosis or scar. Since the difference between normal and abnormal myocardium is based on washout kinetics, images that are delayed by 5 to 20 minutes after contrast injection will optimally depict the fibrosis or scar.

The differences in gadolinium enhancement on MRI of viable myocardium and fibrosis or scar have been known for many years. Recently, however, MRI pulse sequences have been developed that greatly improve the conspicuity of the enhanced areas of myocardium that have been replaced by fibrosis or scar. The pulse sequence used is an inversion-recovery prepared gradient-echo sequence. In this method, an inversion pulse is used to null the signal from normal myocardium. Myocardium that is replaced by fibrosis or scar retains gadolinium and shows very high signal intensity compared with the suppressed, darker myocardium.

Gadovist has been the standard gadolinium contrasts used in the U.S. in CMR imaging for the past few years. On the other hand, Dotarem, a widely used contrast agent in Europe, has been introduced to be used in the U.S. market.The sensitivity of Dotarem to that of Magnevist in determining the location and extent of scar in patients scanned with CMR will be Gadovist in this study.

The CMR laboratory at the Houston Methodist DeBakey Heart & Vascular Center is one of the largest dedicated CMR laboratories in the U.S. performing 3,000 clinical CMR procedures per year. The laboratory has been in existence since 2008 and is currently equipped with 2 dedicated MRI scanners: 1.5T Siemens Avanto and 3.0T Siemens Verio. Through a research agreement with Siemens Medical Solutions, the laboratory has access to numerous works-in progress sequences as they are developed. The laboratory is equipped with an MRI compatible patient monitoring system, infusion pump, and power injector and is staffed by a team of 5 dedicated CMR technologists, 2 clinical nurses, 1 CMR fellow, an MRI scientist, and 2 attending cardiologists.

One hundred twenty patients with known or suspected cardiovascular disease will be recruited for this study. Patients will be randomized (in a 1:1 fashion) to receive either Dotarem or Gadovist for LGE-CMR such that there will be 60 patients in the Dotarem cohort and 60 patients in the Gadovist cohort.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients undergoing clinically referred CMR.

Exclusion Criteria:

1. Patients who are unable to give informed consent.
2. Individuals with severe claustrophobia.
3. Individuals unable to lie flat for 90 minutes (the anticipated amount of time to complete the MRI procedure).
4. Individuals who are pregnant.
5. Patients with implants or pacemakers.
6. Patients that have hypersensitivity to components of gadolinium.
7. Patients with renal failure.
8. Patients who had any trauma or surgery which may have left ferromagnetic material in the body.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3.0 Tesla Cardiac MRI using Dotarem contrast agent; 60 randomly selected participants with suspected or known cardiovascular disease will have a 3.0 Tesla Cardiac MRI with contrast agent, Dotarem	Drug: Cardiac MRI taken using contrast agent, Dotarem® (Gd-DOTA); Gadolinium based contrast agent used in cardiac MRI scanning using 3.0 Tesla MRI; Other Names: Cardiac MRI with contrast; CMR with tracer or contrast agent; Dotarem (Gd-DOTA) contrast agent; Drug: Cardiac MRI with contrast agent, Gadovist; Brand of Gd-DO3A-butrol; contrast agent used in cardiac MRI scanning using 3.0 Tesla MRI; Other Names: Cardiac MRI with contrast; CMR with tracer or contrast agent; Gadovist® (Gd-DO3A-butrol) contast agent
Experimental: 3.0 Tesla Cardiac MRI using a Gadovist contrast agent; 60 randomly selected participants with suspected or known cardiovascular disease will have a 3.0 Tesla Cardiac MRI with contrast agent, Gadovist	Drug: Cardiac MRI taken using contrast agent, Dotarem® (Gd-DOTA); Gadolinium based contrast agent used in cardiac MRI scanning using 3.0 Tesla MRI; Other Names: Cardiac MRI with contrast; CMR with tracer or contrast agent; Dotarem (Gd-DOTA) contrast agent; Drug: Cardiac MRI with contrast agent, Gadovist; Brand of Gd-DO3A-butrol; contrast agent used in cardiac MRI scanning using 3.0 Tesla MRI; Other Names: Cardiac MRI with contrast; CMR with tracer or contrast agent; Gadovist® (Gd-DO3A-butrol) contast agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare visual image quality of LGE-CMR when performed with Dotarem or Gadovist in a randomized fashion.	All LGE-CMR scans scoring for visual image quality using a 5-point scale: 1 = LV myocardium not visible, 2 = severe artifact interfering with ability to visualize LV myocardial borders limiting assessment for presence of LGE (poor), 3 = LV myocardial borders are well delineated but there is moderate artifact affecting ability to identify LGE (fair), 4 = LV myocardium is well delineated with minor artifacts affecting ability to identify LGE (good), 5 = LV myocardium well delineated with no artifacts affecting ability to identify LGE (excellent).	Two years
Compare quantitative signal enhancement of LGE when performed with Dotarem or Gadovist in a randomized fashion.	Assessment of the intensity of hyperenhancement with Dotarem and Gadovist using a semi-automated computer software.	Two Years
Compare association of LGE and clinical cardiovascular outcomes when performed with Dotarem or Gadovistin a randomized fashion.	Patient screened for outcomes (e.g. acute myocardial infraction, sudden cardiac death, heart failure, stroke, cardiovascular hemorrhage, other death from cardiovascular causes)	Eight years

Collaborators and Investigators

• Sponsor: Dipan Shah
• Collaborators: Guerbet
• Investigators: Principal Investigator: Dipan Shah, MD, The Methodist Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: January 18, 2017
• First Submitted That Met QC Criteria: February 15, 2017
• First Posted (Actual): February 20, 2017

Study Record Updates

• Last Update Posted (Actual): January 22, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: CAD
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Cardiomyopathies; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
• Other Study ID Numbers: Pro00012234

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No