Cardiac Diseases
Conditions
Keywords
Echo, Echocardiogram, Cardiac ultrasound, Suboptimal, Contrast agent, Enhancing agent, LVO, LVEBD
Brief summary
This is a phase III, prospective, multicenter, open-label, crossover study of the safety and efficacy of NH002-enhanced echocardiography in adult subjects with suboptimal images on non-contrast 2D transthoracic echocardiography with harmonic imaging within 30 days ahead of NH002 administration. The efficacy for two different modes of administration (i.e., IV bolus injection and infusion) will be evaluated independently.
Interventions
NH002 is formulated as a microbubble injectable suspension for intravenous administration. NH002 requires an activation process prior to use.
Sponsors
Trust Bio-sonics, Inc.
Syneos Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or older 2. Ability to understand and the willingness to provide written informed consent 3. Having or suspected of having cardiac disease 4. Undergone a transthoracic echo within 30 days prior to NH002 dose administration, resulting in suboptimal LVEBD, as defined by 2 or more segments of 6 segments of the ventricular border that cannot be visualized reliably in any of the standard apical 4-, 2-, and 3-chamber views during the resting non-contrast ultrasound examination
Exclusion criteria
1. Any evidence of other severe or unstable cardiopulmonary and/or systemic hemodynamic conditions deemed unsuitable for the study by the investigator(s) prior to NH002 dose administration, including, but not limited to: 1. ongoing or recent acute coronary syndrome within 6 months 2. uncontrolled serious ventricular arrhythmias 3. decompensated or inadequately controlled congestive heart failure (New York Heart Association Class IV) 4. atrial fibrillation or current uncontrolled cardiac arrhythmias causing symptoms or hemodynamic compromise 5. uncontrolled hypertension (i.e., resting systolic blood pressure \>200 mmHg, diastolic blood pressure \>110 mmHg, or arterial hypotension \[defined as systolic blood pressure ≤ 90 mmHg\]) 6. acute aortic dissection 2. Known or suspected hypersensitivity to one or more of the ingredients of NH002, perflutren, Definity, or other echocardiographic contrast agents 3. Known or suspected hypersensitivity to PEG, prior reactions to common PEG-containing products such as colonoscopy bowel preparations, and certain laxatives (e.g., Miralax) 4. Received an investigational compound within 30 days before enrolling in the study 5. Received any contrast agent either intravascularly or orally within 48 hours prior to NH002 dose administration 6. Pregnant or lactating female. Exclude the possibility of pregnancy: 1. testing on-site at the institution (serum or urine β-human chorionic gonadotropin) within 7 days prior to the start of NH002 dose administration, and 2. history of using an adequate and medically approved method of contraception to avoid pregnancy for at least 1 month prior to NH002 dose administration and willing to continue using the same method for the duration of the study, or 3. surgical history (e.g., tubal ligation or hysterectomy), or 4. postmenopausal with a minimum of 1 year without menses. 7. Serious medical or psychiatric illness/condition likely, in the judgment of the investigator, to interfere with compliance with protocol treatment/research
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Endocardial Border Delineation (LVEBD) | Image data obtained pre-injection and within 15 minutes post-injection | The first primary efficacy endpoint will be the change from baseline (prior to each dose of NH002 administration) in total LVEBD scores (UEUS vs CEUS) defined using a 16-segment model derived from the standard 17-segment model, as assessed through blinded central reading. The LV endocardium of the standard apical 4-, 2-, and 3-chamber views is divided into 6 segments, with 2 basal, mid-, and apical segments in each view, of which 2 segments are shared in the standard apical 4- and 3-chamber views (i.e., a total of 16 segments in the 3 views). The 17th segment at the apex will not be scored since it does not connect to any part of the LV endocardial border. For each segment, LVEBD is graded as follows: 0 = inadequate border (border not visible); 1 = sufficient (border barely visible); 2 = good (border clearly visible). A total delineation score (0 to 32) is obtained by adding the scores from a total of the 16 segments in the 3 views. |
| Left Ventricular Opacification (LVO) | Image data obtained pre-injection and within 15 minutes post-injection | The co-primary endpoint will be the proportion of subjects with adequate LVO defined by an LVO grade of +2 (moderate) or +3 (complete), as assessed through blinded central reading. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The number and percentage of subjects with suboptimal echocardiography converted into optimal echocardiography | Image data obtained pre-injection and within 15 minutes post-injection | Objective evaluation of the number and percentage of subjects with suboptimal echocardiography (based on the definition of inadequate LVEBD, i.e., at least two segments \[in any chamber view\] with an LVEBD score of 0) converted into optimal echocardiography following administration of study drug will be summarized for each reader. |
| Standard 12-lead ECGs | From pre-injection (before the first dose) to 24 hours (after the end of second dose) | Standard 12-lead ECGs assessed prior to injection and at 10 and 30 minutes after the initiation of IV bolus injection and infusion; and at 24 hours after the end of the second dose of NH002 |
| Blood Pressure (BP) | From pre-injection (before the first dose) to 24 hours (after the end of second dose) | Change in BP assessed prior to injection and at 5, 10 and 30 minutes after the initiation of IV bolus injection and infusion; and at 24 hours after the end of the second dose of NH002 |
| Heart Rate (HR) | From pre-injection (before the first dose) to 24 hours (after the end of second dose) | Change in HR assessed prior to injection and at 5, 10 and 30 minutes after the initiation of IV bolus injection and infusion; and at 24 hours after the end of the second dose of NH002 |
| SpO2 | From pre-injection (before the first dose) to 24 hours (after the end of second dose) | SpO2 assessed by pulse oximetry prior to injection and at 5, 10 and 30 minutes after the initiation of IV bolus injection and infusion; and at 24 hours after the end of the second dose of NH002 |
| Physical Examination (PE) | From pre-injection (before the first dose) to 24 hours (after the end of second dose) | PE assessed prior to injection and at 30 minutes after the initiation of IV bolus injection and infusion; and at 24 hours after the end of the second dose of NH002 |
| Adverse Events (AEs) | From pre-injection (before the first dose) to 24 hours (after the end of second dose) | AEs assessed prior to injection and at 5, 10, 15 and 30 minutes after the initiation of IV bolus injection and infusion; and at 24 hours after the end of the second dose of NH002 |
Outcome results
None listed