Clinical trial NCT03882359: An Ascending Dose Comparison of MVT-100 to Definity in Healthy Volunteers
Official title: MVT-100: Advancing the Clinical Use of Perflutren Ultrasound Contrast Agents for Suboptimal Echocardiograms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Heart Diseases
Keywords: echo
echocardiogram
Healthy Volunteers
Definity
Lead sponsor: Microvascular Therapeutics, LLC
Sponsor class: INDUSTRY
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: University of Nebraska
First posted: 2019-03-20
Enrollment: 16
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Ascending dose comparison in healthy volunteers
Primary purpose: DIAGNOSTIC

Brief summary: Definity (perflutren lipid microspheres, Lantheus Medical Imaging) is an ultrasound contrast indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. MVT-100 (the investigational pharmaceutical) is similar to Definity, with the exception of the removal of one lipid in the lipid blend and substitution of another lipid. This study is intended to evaluate the safety and efficacy of MVT-100 using a single ascending dose design in healthy volunteers. Patients are randomized to receive either MVT-100 or Definity and undergo echocardiograms after receiving either MVT-100 or Definity via bolus or IV infusion administration. The primary endpoints evaluated are safety and endocardial border delineation.

Detailed description: Ultrasound is one of the most common imaging examinations and has advantages of absence of ionizing radiation, portability and relatively low cost. Ultrasound contrast agents are used to improve the accuracy of ultrasound and Definity (perflutren) is the world's leading ultrasound contrast agent but perflutren has to be refrigerated and has a side effect of back pain. The investigators have developed a new, improved perflutren, MVT-100, with potential for room temperature storage.

Ultrasound contrast agents are used to increase the backscatter (signal intensity of blood vessels and tissues to improve diagnostic accuracy) of ultrasound imaging. In the US ultrasound contrast agents are FDA approved for echocardiography to improve endomyocardial border definition.

MVT-100 reflects the ultrasound to provide strong back-scattering. MVT-100 microbubbles resonate with ultrasound to provide strong harmonic signals. MVT-100 microbubbles will cavitate with higher levels of ultrasound and cavitation may be stable or inertial depending upon acoustic parameters and other factors.

The study is a multi centre ascending dose comparison of Definity and MVT-100 for use in echocardiography and will be performed in a sample of healthy volunteers who are randomized to receive either Definity or MVT-100.

This trial will assess safety and evaluate the following imaging metrics:

* Determine the optimal dose of MVT-100 by comparing MVT-100 vs Definity in the change from baseline of quantitative left ventricular opacification
* Evaluation of qualitative left ventricular opacification (LVO)
* Evaluation of endocardial border delineation
* Evaluation of endocardial border length
* Evaluation of duration of useful contrast

Eligibility criteria: Inclusion Criteria:

* Adult subjects 19 years of age or older, male or female
* Female subjects must no longer have child-bearing potential (\>1-year post menopause or surgically sterilized), or must

  * have a negative urine pregnancy test, and
  * be using and continue to use for 30 days after the study a medically effective method of contraception
* Adequate hematologic, renal and hepatic function, as defined by:
* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
* Platelet count ≥ 100 x 109/L
* Hemoglobin ≥ 90 g/L
* Plasma creatinine\< 1.5 x ULN
* Total bilirubin within normal limits (\< 2.5 x ULN if Gilbert's syndrome)
* Aspartate transaminase (AST) and Alanine transaminase (ALT) \< 2.5 x ULN
* Subject must be willing and able to understand the study and provide written Informed Consent to participate in the study

Exclusion Criteria:

* Myocardial infarction within six months prior to enrollment
* Unstable angina, NYHA Class II or greater congestive heart failure
* EKG evidence of uncontrolled arrhythmia or history of clinically significant arrhythmia within the past six months
* Clinically significant Chronic Obstructive Pulmonary Disease (COPD) or other pulmonary condition that is not controlled by medication or requires oxygen frequently or continuously
* A history of pulmonary emboli
* Known hypersensitivity to perflutren, DEFINITY® or other echo contrast agent
* Inability to remain supine for 60 minutes
* Oxygen saturation \< 95% on room air
* History of allergic reaction attributed to compounds of similar chemical composition to MVT-100 or DEFINITY® or soy or egg allergies (see Investigator's Brochure)
* Subject has received any investigational drug within thirty (30) days prior to enrollment into the study
* Inability to comply with study procedures
* Subjects with any medical condition deemed by the investigator to make the subject inappropriate for participation

Primary outcomes:
measure: QT Interval
timeFrame: Day of study
measure: Blood Pressure
timeFrame: Day of study
measure: Heart Rate
timeFrame: Day of study
measure: Oxygen Saturation
timeFrame: Day of study
measure: Other Symptoms
timeFrame: Day of study
Secondary outcomes:
measure: Left Ventricular Opacification (LVO)
timeFrame: Day of Study
measure: Cardiac Segment Visualization
timeFrame: Day of Study
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
References:
citation: Smith-Bindman R, Miglioretti DL, Johnson E, Lee C, Feigelson HS, Flynn M, Greenlee RT, Kruger RL, Hornbrook MC, Roblin D, Solberg LI, Vanneman N, Weinmann S, Williams AE. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012 Jun 13;307(22):2400-9. doi: 10.1001/jama.2012.5960.
citation: Platts DG, Luis SA, Roper D, Burstow D, Call T, Forshaw A, Pascoe R. The safety profile of perflutren microsphere contrast echocardiography during rest and stress imaging: results from an Australian multicentre cohort. Heart Lung Circ. 2013 Dec;22(12):996-1002. doi: 10.1016/j.hlc.2013.05.637. Epub 2013 Jun 10.
citation: Weissman, Neil J., Warren J. Manning, and Brian C. Downey. Contrast echocardiography: clinical applications. Waltham, MA : UpToDate, 2013.
citation: Lantheus Medical Imaging. Definity Package Insert. Definity Imaging. [Online] http://www.definityimaging.com/pdf/DEFINITY_US_PI_515987-0117.pdf.
citation: Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG; American Society of Echocardiography. American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc Echocardiogr. 2007 Sep;20(9):1021-41. doi: 10.1016/j.echo.2007.07.003. No abstract available.
citation: Porter TR, Abdelmoneim S, Belcik JT, McCulloch ML, Mulvagh SL, Olson JJ, Porcelli C, Tsutsui JM, Wei K. Guidelines for the cardiac sonographer in the performance of contrast echocardiography: a focused update from the American Society of Echocardiography. J Am Soc Echocardiogr. 2014 Aug;27(8):797-810. doi: 10.1016/j.echo.2014.05.011. No abstract available.