Clinical trial NCT01721447
Conditions: Atrial Fibrillation
Keywords: Atrial fibrillation stroke TEE Left atrial thrombus
Sponsor: University of Utah
Start date: 2013-06-01; Completion date: 2018-05-01
Enrollment: 100 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The investigators intend to determine if using Optison echocardiography contrast increases sensitivity and specificity of detecting left atrial appendage thrombus in transesophageal echocardiography studies as opposed to standard 2D and 3D TEE imaging without the use of echo contrast.

Detailed description:
Accurate determination of the presence or absence of left atrial appendage (LAA) thrombus has a large impact on the clinical course of patients with atrial fibrillation or ischemic stroke and has large financial implications as well. Misdiagnosing the presence of LAA thrombus can lead to unnecessarily cancelled procedures (cardioversion and atrial fibrillation ablation) and potentially hazardous, unnecessary changes in clinical care (such as prolonged Coumadin anticoagulation). Missing LAA thrombus can result in continuation of cardioversion or atrial fibrillation ablation procedures at a time when there is higher risk of subsequent embolic stroke.

Several of the patients with atrial fibrillation require transesophageal echocardiography (TEE) performed prior to cardioversion or atrial fibrillation ablation procedures. There is opportunity to enroll most of these patients in our proposed study. There has been essentially no work published about the use of echo contrast materials in TEE (other than agitated saline), particularly the use of Optison. Thus, the investigators will be exploring a new field in echocardiography and echo contrast.

Arms: arm 1: Subjects with atrial fibrillation who are undergoing a TEE procedure will be assessed using Optison echocardiography contrast agent
Interventions: intervention 1: Optison echocardiography contrast agent
Intervention descriptions: intervention 1: Subjects undergoing transesophageal echocardiography who will receive the Optison contrast agent during the procedure to test if the image quality improves to provide accurate assessment of the presence of left atrial thrombus.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
The Use of Optison Echocardiography Contrast in the  
Detection of Left Atrial Appendage Thrombus with 
Transesophageal Echocardiography 
 
 
NCT01721447 
 
Document Date: 03/20/2018 


Protocol Summary (ERICA) 
 
IRB_00058561 
Page 1 of 6 
 
IRB Approval 4/22/2015 
 
 
The use of Optison echocardiography contrast in the 
detection of left atrial appendage thrombus with 
transesophageal echocardiography.   
 
Protocol Summary 
 
 
 
IRB Approval Date of Current Version: 3/20/2018 
University of Utah IRB #: IRB_00058561 
Sponsor: GE HEALTHCARE 
  
Principal Investigator: Brent Wilson 
Internal Staff and  Sub-Investigators: 
Erik Bieging 
LeeAnn Bywaters 
anna catino 
Lowell Chang 
Miriel Collins 
Majd (Mark) Ibrahim 
Ashlee Rooks 
Rashmee Shah 
Promporn Suksaranjit 
Brandon Sullivan 
Robert Watkins 
Paige Wilson 
External Sub-Investigators: 
 
 
This document was created using the ERICA Online System at the University of Utah. The document is created 
from study information approved by the IRB on the date listed above.  Any alteration to the original content of this 
document may not be considered to represent the study as approved by the IRB.  
 
 


Protocol Summary (ERICA) 
 
IRB_00058561 
Page 2 of 6 
 
IRB Approval 4/22/2015 
 
Background and Introduction 
 
Accurate determination of the presence or absence of left atrial appendage (LAA) 
thrombus has a large impact on the clinical course of patients with atrial fibrillation or 
ischemic stroke and has large financial implications as well.  Misdiagnosing the presence 
of LAA thrombus can lead to unnecessarily cancelled procedures (cardioversion and atrial 
fibrillation ablation) and potentially hazardous, unnecessary changes in clinical care (such 
as prolonged Coumadin anticoagulation).  Missing LAA thrombus can result in continuation 
of cardioversion or atrial fibrillation ablation procedures at a time when there is higher 
risk of subsequent embolic stroke. 
The University of Utah is home to the CARMA Center (Comprehensive Arrhythmia 
Research and Management) and is a high volume center for the treatment of atrial 
fibrillation.  Many of these patients require transesophageal echocardiography (TEE) 
performed by our echocardiography laboratory prior to cardioversion or atrial fibrillation 
ablation procedures, and most of them undergo cardiac MRI studies as well.  There is 
opportunity to enroll most of these patients in our proposed study.  There has been 
essentially no work published about the use of echo contrast materials in TEE (other than 
agitated saline), particularly the use of Optison.  Thus, we will be exploring a new field in 
echocardiography and echo contrast.  
 
 
 
Purpose and Objectives 
 
Our objective is to determine if using Optison echocardiography contrast increases 
sensitivity and specificity of detecting left atrial appendage thrombus in transesophageal 
echocardiography studies as opposed to standard 2D and 3D TEE imaging without the use 
of echo contrast.   
 
 
 
Study Population 
 
Age of Participants: 18+ 
 
Sample Size: 
At Utah: 
500  
All Centers: 
500 
 
Inclusion Criteria: 
 
Patients referred to the University of Utah Echocardiography Lab for for a 
transesophageal echocardiography (TEE) will be included in the study. 
Subjects must be 


Protocol Summary (ERICA) 
 
IRB_00058561 
Page 3 of 6 
 
IRB Approval 4/22/2015 
 
(1) > 18 years old 
(2) Able to provide consent 
(3) Indicated for TEE as a standard clinical procedure to evaluate cardiac health status 
  
 
Exclusion Criteria: 
 
Patients will be excluded for meeting the contraindications for Optison administration. 
1. Known right-to-left, or bi-directional cardiac shunts.  
2. Hypersensitivity to perflutren, blood, blood products or albumin.  
3. Women who pregnant (since Optison may have effects on the fetus that are currently 
unknown).  
4. Removal of Left Atrial Appendage.  
5. Not able to provide Informed Consent. 
 
 
Design  
 
Prospective Clinical Research 
 
 
 
 
 
Study Procedures 
 
Recruitment/Participant Identification Process: 
Potential participants for the study will be recruited from the Cardiology/Electrophysiology 
(EP) clinic during normally scheduled clinic visits. No other recruitment procedures (phone 
call / recruitment letters) will be used in this study.  In-person contact by the PI /sub-I or 
other cardiologists (made aware of study by word of mouth) who refer their patients into 
the study will be the primary mode of recruitment. Prior to approaching the subject, the 
PI/research staff will conduct a chart review to confirm that the potential subject fits the 
eligibility criteria for the study. 
Potential participants will be screened by the PI/Co-PI and other cardiologists who are 
aware of the study and refer the subject to the study. When the patient is being seen in 
the clinic for a routine follow-up visit, if the patient fits with all the eligibility criteria 
during chart review (prior to clinician seeing the patient), then the PI/sub-I/ clinician will 
approach the potential participant and discuss the study with them. 
  


Protocol Summary (ERICA) 
 
IRB_00058561 
Page 4 of 6 
 
IRB Approval 4/22/2015 
 
If the potential subject is interested in participation, the  PI/Co-PI will consent the subject 
or call the Study Coordinator (SC) /Clinical Research Manager (CRM) to conduct the 
informed consent process with the participant. The PI/sub-I may be present during the 
process. However, if they are not able to be physically present, the SC /CRM will report to 
the PI/Sub-I immediately after consent to confirm the appropriate conduct of the process. 
 
 
Informed Consent: 
Description of location(s) where consent will be obtained:  
University of Utah Hospital and Clinics, specifically the ECHO clinic. 
 
Description of the consent process(es), including the timing of consent:  
Patients will be approached at the University of Utah Hospital and Clinics on the day that 
they are already scheduled to undergo their standard of care TEE for their specific clinical 
problem. If patients are found to fit with the eligibility criteria outlined for the study, they 
will be approached and the study discussed with them. The clinician may consent the 
patient themselves, or call the study coordinator / clinical research manager to conduct 
the consent process. The person who is conducting the consent process will provide a 
detailed description of the study, the study-related procedures, time that the participant 
will have to spend for the study, the benefits and risks of participation, the costs and 
compensations involved in the study, the contacts for the PI, IRB and the research 
participant advocate. The University of Utah's stand on research-related injuries will be 
explained and the participant's questions will be answered. The participant will be 
provided with a copy of the consent form and given as much time as they require to go 
over the consent and to make an informed decision. Participants who require extra time 
will be given the option to call the study team back. All this information and the consent 
process will be documented in the staff notes section of each participant's folder. If the 
study coordinator / clinical research manager conduct the informed consent process, then 
the PI / sub-I who identified the eligible participant will sign the informed consent form 
right below the signature of the person who conducted the informed consent process after 
confirmation that the informed consent process was completed in an appropriate and 
satisfactory manner. 
 
Procedures: 
1. Patients will be identified and pre-screened using electronic medical records. Final 
screening and consent will be conducted in clinic, generally on the day that they were 
already scheduled to undergo a standard of care TEE for their specific clinical condition.  
2. If the patient is found to be eligible based on inclusion/exclusion criteria, the 
investigator and/or study coordinator will approach them and explain the study. 
  
3. If the patient agrees to participate and provides informed consent, then we fill out an 
enrollment sheet, create their study file and gather the necessary information from the 
patient. 
  


Protocol Summary (ERICA) 
 
IRB_00058561 
Page 5 of 6 
 
IRB Approval 4/22/2015 
 
4. Patient will then undergo their scheduled TEE without optison contrast. The clinician 
will determine whether it is possible to clearly identify the presence or absence of left 
atrial appendage thrombus from the standard TEE images.  
  
5. If the presence or absence of thrombus cannot be clearly determined with standard 
TEE, the clinician will administer optison contrast and then continue the examination to 
try to obtain a conclusive result. 
  
6. Data will then be collected, including ECHO reports, cardiac MRI reports, medical 
history, adverse events etc. as compiled during the procedure visit. Data will only be 
collected if the patient receives Optison during the TEE procedure. 
  
7.  Three months following the TEE, the medical record of the patients that received 
Optison will be reviewed for any additional adverse events or thrombii detection via other 
method.  The end point of the study will be the collection of pertinent data, three months 
following TEE. 
  
Statistical analysis will be conducted utilizing the statistical resources available to us 
through the CCTS. 
 
Optison will be used for its approved indications (as an ultrasound contrast agent) and in 
compliance with the U.S. Food and Drug Administration (FDA) safety guidelines. Optison 
is a contrast agent used in ECHO studies, and does not involve any radiation/radioactive 
substances. The ECHO procedure does not expose patients to ionizing radiation, and 
Optison or ultra sound contrast agents do not contain dye or increase a patient's risk of 
nephrotoxicity. Ultrasound contrast agents are safe and completely radiation-free 
diagnostic imaging tools. 
 
 
Procedures performed for research purposes only:  
Administration of Optison echocardiography contrast and re-imaging using standard 2
and 3D techniques will be the research-related procedure.  The participant will be 
undergoing the Echocardiography for clinical indications and additional echo with optis
contrast will be provided along with participant's clinical echo. 
 
 
Statistical Methods, Data Analysis and Interpretation 
 
Descriptive presentation of continuous variables and chi-squared / Fisher-exact tests for 
frequency variables.  Since this study is a descriptive, pilot study to see utility of Optison 
in echocardiography, the contrast agent will be used in 100 patients to see at what 


Protocol Summary (ERICA) 
 
IRB_00058561 
Page 6 of 6 
 
IRB Approval 4/22/2015 
 
frequency the contrast agent is able to identify LAA thrombi. The contrast agent is already 
being used in echo, we are using it as it is approved by the FDA. A future larger RCT 
study will be construed using this pilot data. 
While we intend to gather optison TEE data from 100 subjects, our enrollment cap has to 
be higher than that. Only those subjects whose standard TEE's are inconclusive will be 
administered optison, and subjects will need to be consented prior to the start of the 
standard TEE. Because only a minority of enrolled patients will receive optison, we plan to 
enroll 500 patients.