Comparison of the Sensitivity and Specificity of Acoustic Angiography to the Sensitivity and Specificity of Conventional Ultrasound

• Sponsor: UNC Lineberger Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02175628
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 49
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Purpose: This study will evaluate a new ultrasound imaging technology called acoustic angiography. Acoustic angiography uses an ultrasound contrast agent, already FDA approved for use in cardiology, to enhance imaging of blood vessels. Since acoustic angiography uses ultrasound, and not x-rays, the patient is not exposed to ionizing radiation, unlike traditional angiography and mammography. Specific goals will be to evaluate the quality of the images provided by acoustic angiography in the human breast, and furthermore to evaluate whether or not acoustic angiography provides additional diagnostic information over traditional ultrasound which could provide an improvement in assessing breast lesions. Specifically, this additional diagnostic information will hopefully enable us to reduce false positive tests and discriminate lethal cancers from non-lethal disease.

Participants: The investigators are recruiting 60 patients from the UNC Breast Clinic who are undergoing core needle biopsy or surgical biopsy (BIRADS 4 and 5 breast lesions).

Procedures (methods): Acoustic Angiography imaging will be performed in conjunction with standard diagnostic imaging, including b-mode ultrasound . Then, a reader study will be conducted to compare these modalities. Finally, the images will be analyzed with image processing techniques to determine quantitative metrics exhibited by the blood vessel morphology in the images. These metrics will be utilized to develop a "malignancy score" equation to predict malignancy of a lesion.

Condition or Disease	Intervention/Treatment	Phase
Signs and Symptoms	Device: Acoustic Angiography	N/A

Detailed Description

Increasing the sensitivity and specificity of diagnostic imaging in patients at high risk for breast cancer could provide substantial clinical benefit by improving diagnosis, preventing over-treatment, and reducing healthcare costs. Acoustic angiography is a new type of contrast enhanced ultrasound imaging which is specifically sensitive to microvascular structure and density. It evaluates tumor micro-vasculature and may provide a powerful prognostic tool for the diagnosis of breast cancer, and eventually for treatment evaluation.

Sixty patients who are to have a clinical surgical breast biopsy based on results from pre-study standard of care (SOC) imaging will be recruited from the UNC Breast Clinic for participation in the study. The primary objective of this single arm study is to compare the sensitivity and specificity of acoustic angiography with traditional b-mode ultrasound in the distinction of malignant versus benign breast lesions. Secondary objectives include a comparison of area under the curve (AUC) for acoustic angiography versus b-mode ultrasound, comparison of radiologist preference for the two imaging techniques for each of 3 lesion characteristics, and quantification of vessel tortuosity based on acoustic angiography imaging results. These metrics will be used to develop a predictive model of malignancy which will subsequently be compared to results from radiology review.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Comparison of the Sensitivity and Specificity of Acoustic Angiography (Micro-tumor Detection by Quantifying Tumor-induced Vascular Abnormalities) to the Sensitivity and Specificity of Conventional Ultrasound
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Jun 30, 2018
• Actual Study Completion Date: Jun 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acoustic Angiography All breast patients will be included in the experimental group.	Device: Acoustic Angiography; Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.
Experimental: Healthy Volunteers A volunteer group was added to the study to perfect the image acquisition techniques.	Device: Acoustic Angiography; Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.

Outcome Measures

Primary Outcome Measures

1. Sensitivity and Specificity (Percentage) [1.5 years]

   To compare (using a reader study) the sensitivity and specificity of acoustic angiography to the sensitivity and specificity of conventional b-mode ultrasound in evaluation of breast lesions

Secondary Outcome Measures

1. Area Under the Curve (AUC) of Acoustic Angiography [1.5 years]

   The AUC of acoustic angiography compared to the AUC of b-mode ultrasound

2. Radiologist Preference [1.5 years]

   To compare radiologist preference of acoustic angiography to conventional b-mode ultrasound for each lesion characteristic (shape, margins and vascularity)

3. Vessel Tortuosity (No Units) [1.5 years]

   To quantify vessel tortuosity metrics for the acoustic angiograph images, and to use these metrics to develop a model for predicting malignancy (a model-based malignancy score)

4. Model-based Malignancy Score (Arbitrary Units) [1.5 years]

   To compare the model-based malignancy score to the acoustic angiography reader study

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women ≥18 years old

• Scheduled for breast core needle or surgical biopsy of at least one breast lesion based on suspicious breast lesion (BIRADS score of 4 or 5) from pre-study SOC imaging studies

• Center of suspicious lesion is not deeper than 1.5 cm, and the diameter of the lesion is not greater than 2 cm

• Able to provide informed consent

• Negative urine pregnancy test in women of child-bearing potential

Exclusion Criteria:

• Male (it is uncommon for men to present for imaging and the overwhelming majority of findings are non-cancerous and do not lead to biopsy; male breast cancer represents <1% of newly diagnosed breast cancer)

• Institutionalized subject (prisoner or nursing home patient)

• Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD)

• Known hypersensitivity to sulfur hexafluoride or to any component of perflutren lipid (Definity®)

• Right to left shunt, severe pulmonary hypertension (pulmonary artery pressure

90mmHg), or adult respiratory distress syndrome

• Active cardiac disease including any of the following:

• Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association)

• Unstable angina.

• Severe arrhythmia (i.e. ventricular tachycardia, flutter fibrillation; ventricular premature complexes occurring close to the preceding T-wave, multifocal complexes).

• Myocardial infarction within 14 days prior to the date of proposed Definity® administration.

• Uncontrolled systemic hypertension (systolic blood pressure (BP) >150 mm Hg and/or diastolic BP >90 mm Hg despite optimal medical management

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UNC Hospital	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• UNC Lineberger Comprehensive Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Yueh Lee, MD, PhD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 17, 2017
• Informed Consent Form - May 1, 2018

More Information

Publications

None provided.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT02175628
• Other Study ID Numbers: LCCC1405; R01CA170665
• First Posted: Jun 26, 2014
• Last Update Posted: Aug 5, 2019
• Last Verified: Oct 1, 2018

• Keywords provided by UNC Lineberger Comprehensive Cancer Center: Ultrasound; Breast; Angiography
• Additional relevant MeSH terms: Hypersensitivity

Study Results

Participant Flow

Arm/Group Title	Acoustic Angiography	Healthy Volunteers
Arm/Group Description	All breast patients will be included in the experimental group. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.	A volunteer group was added to the study to perfect the image acquisition techniques. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.
Period Title: Overall Study
STARTED	6	17
COMPLETED	6	17
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Acoustic Angiography	Healthy Volunteers	Total
Arm/Group Description	All breast patients will be included in the experimental group. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.	A volunteer group was added to the study to perfect the image acquisition techniques. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.	Total of all reporting groups
Overall Participants	6	17	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 83.3%	15 88.2%	20 87%
>=65 years	1 16.7%	2 11.8%	3 13%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48 (14)	43 (17)	45 (17)
Sex: Female, Male (Count of Participants)
Female	6 100%	14 82.4%	20 87%
Male	0 0%	3 17.6%	3 13%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 5.9%	1 4.3%
Not Hispanic or Latino	6 100%	8 47.1%	14 60.9%
Unknown or Not Reported	0 0%	8 47.1%	8 34.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 33.3%	2 11.8%	4 17.4%
White	4 66.7%	5 29.4%	9 39.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	10 58.8%	10 43.5%
Region of Enrollment (participants) [Number]
United States	6 100%	17 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	Sensitivity and Specificity (Percentage)
Description	To compare (using a reader study) the sensitivity and specificity of acoustic angiography to the sensitivity and specificity of conventional b-mode ultrasound in evaluation of breast lesions
Time Frame	1.5 years

Outcome Measure Data

Analysis Population Description

The data were unable to be analyzed because we could not visualize the vessels to calculate this value. The system was unable to achieve the imaging resolution to visualize the vasculature.

Arm/Group Title	Acoustic Angiography	Healthy Volunteers
Arm/Group Description	All breast patients will be included in the experimental group. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.	A volunteer group was added to the study to perfect the image acquisition techniques. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.
Measure Participants	0	0

2. Secondary Outcome

Title	Area Under the Curve (AUC) of Acoustic Angiography
Description	The AUC of acoustic angiography compared to the AUC of b-mode ultrasound
Time Frame	1.5 years

Outcome Measure Data

Analysis Population Description

The data were unable to be analyzed because we could not visualize the vessels to calculate this value. The system was unable to achieve the imaging resolution to visualize the vasculature.

Arm/Group Title	Acoustic Angiography	Healthy Volunteers
Arm/Group Description	All breast patients will be included in the experimental group. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.	A volunteer group was added to the study to perfect the image acquisition techniques. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.
Measure Participants	0	0

3. Secondary Outcome

Title	Radiologist Preference
Description	To compare radiologist preference of acoustic angiography to conventional b-mode ultrasound for each lesion characteristic (shape, margins and vascularity)
Time Frame	1.5 years

Outcome Measure Data

Analysis Population Description

Preference Study not conducted because the imaging resolution was insufficient. The data were unable to be analyzed because we could not visualize the vessels to calculate this value. The system was unable to achieve the imaging resolution to visualize the vasculature.

Arm/Group Title	Acoustic Angiography	Healthy Volunteers
Arm/Group Description	All breast patients will be included in the experimental group. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.	A volunteer group was added to the study to perfect the image acquisition techniques. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.
Measure Participants	0	0

4. Secondary Outcome

Title	Vessel Tortuosity (No Units)
Description	To quantify vessel tortuosity metrics for the acoustic angiograph images, and to use these metrics to develop a model for predicting malignancy (a model-based malignancy score)
Time Frame	1.5 years

Outcome Measure Data

Analysis Population Description

The data were unable to be analyzed because we could not visualize the vessels to calculate this value. The system was unable to achieve the imaging resolution to visualize the vasculature.

Arm/Group Title	Acoustic Angiography	Healthy Volunteers
Arm/Group Description	All breast patients will be included in the experimental group. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.	A volunteer group was added to the study to perfect the image acquisition techniques. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.
Measure Participants	0	0

5. Secondary Outcome

Title	Model-based Malignancy Score (Arbitrary Units)
Description	To compare the model-based malignancy score to the acoustic angiography reader study
Time Frame	1.5 years

Outcome Measure Data

Analysis Population Description

The data were unable to be analyzed because we could not visualize the vessels to calculate this value. The system was unable to achieve the imaging resolution to visualize the vasculature.

Arm/Group Title	Acoustic Angiography	Healthy Volunteers
Arm/Group Description	All breast patients will be included in the experimental group. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.	A volunteer group was added to the study to perfect the image acquisition techniques. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.
Measure Participants	0	0

Adverse Events

Time Frame	30 minutes post imaging
Arm/Group Title	Acoustic Angiography		Healthy Volunteers
Arm/Group Description	All breast patients will be included in the experimental group. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.		A volunteer group was added to the study to perfect the image acquisition techniques. Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner (VisualSonics Vevo 770) and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. All image data will be de-identified and transferred for off-line analysis based on a study ID. The research images will NOT be interpreted or analyzed for clinical decisions related to the patient.
All Cause Mortality
	Acoustic Angiography		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/17 (0%)
Serious Adverse Events
	Acoustic Angiography		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Acoustic Angiography		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.