A Dose Ascending Study to Evaluate the Safety of NH002 as a Contrast Agent in Cardiac Echocardiography

Phase 1

Completed

Conditions: Cardiac Disease

Interventions: Drug: NH002 (Perflutren Lipid Microspheres) Injectable Suspension
Diagnostic Test: Echocardiogram

Registration Number: NCT04185246

Lead Sponsor: Trust Bio-sonics, Inc.

Brief Summary: NH002 (Perflutren Lipid Microspheres) Injectable Suspension is an ultrasound contrast agent for use in patients with suboptimal echocardiograms to opacify the left ventricular (LV) chamber and to improve the delineation of the LV endocardial border. The primary objective of this study is to evaluate the safety and tolerability of 3 ascending doses of NH002.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

Inclusion Criteria

Male or female subjects 20 years of age or older
Ability to understand and the willingness to provide written informed consent
Suspected of having cardiac disease or undergoing evaluation of cardiac anatomy for congenital heart disease
Negative pregnancy test within 24 hours of the procedure if subject is a woman of childbearing potential

Exclusion Criteria

Known right-to-left, bidirectional, or transient right-to-left cardiac shunt(s)
Chronic obstructive pulmonary disease
Ejection fraction at screening or baseline <40%
Uncontrolled serious ventricular arrhythmias or at high risk for arrhythmias due to prolongation of the QT interval (QT corrected by Fridericia's formula >450 msec in males and >470 msec in females)
Clinically significant abnormality in renal and liver function tests (alanine aminotransferase/aspartate aminotransferase >2 × upper limit of normal [ULN]; serum creatinine > 1.5 × ULN)
Known or suspected hypersensitivity to one or more of the ingredients of NH002, perflutren, or other echocardiographic contrast agent
Received an investigational compound within 30 days before enrolling in the study
Received any contrast agent either intravascularly or orally within 48 hours before NH002 administration
Pregnant or lactating female (conception during the study should be avoided)
Serious medical or psychiatric illness/condition likely, in the judgment of the investigator, to interfere with compliance to protocol treatment/research
Clinically unstable cardiopulmonary conditions considered not suitable for participation in the trial, in the judgment of the investigator
Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 200 mmHg or diastolic blood pressure ≥ 110 mmHg) or arterial hypotension (defined as systolic blood pressure ≤ 90 mmHg)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single arm	NH002 (Perflutren Lipid Microspheres) Injectable Suspension	Subjects will be enrolled with sequential allocation to 1 of 3 cohorts with the following intravenous (IV) doses of NH002: 2.5 µl/kg, 5.0 µl/kg, or 10.0 µl/kg. Each patient will undergo an unenhanced ultrasound examination and a NH002 contrast-enhanced examination on the same day
Single arm	Echocardiogram	Subjects will be enrolled with sequential allocation to 1 of 3 cohorts with the following intravenous (IV) doses of NH002: 2.5 µl/kg, 5.0 µl/kg, or 10.0 µl/kg. Each patient will undergo an unenhanced ultrasound examination and a NH002 contrast-enhanced examination on the same day

Primary Outcome Measures

Name	Time	Method
Body Temperature	From pre-injection to 120 minutes post injection	Monitor for any changes in body temperature (in Celsius degree)
Rate of Any Potential Adverse Allergic Reaction	From pre-injection to 240 minutes post-injection	Monitor for any potential adverse allergic reaction
12-lead ECGs	From pre-injection to 60 minutes post injection	Standard 12-lead ECGs will be assessed from pre-injection to 60 minutes post-injection for changes in QT/ corrected QT(QTc) interval (in ms) and ECG morphology; each standard 12-lead ECG assessment will be scored as either normal or abnormal
Respiratory Rate	From pre-injection to 120 minutes post injection	Monitor for any changes in respiratory rate (in breaths/min)
Blood Pressure	From pre-injection to 120 minutes post injection	Monitor for any changes in blood pressure (in mmHg)
Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT)	From pre-injection to 240 minutes post-injection	Monitor for any changes in TT and aPTT
Cardiac Troponin I	pre-injection and 240 minutes post-injection	Monitor for any changes in Cardiac troponin I
Heart Rate	From pre-injection to 120 minutes post injection	Monitor for any changes in heart rate (in beats/min)
Oxygen Saturation by Pulse Oximetry (SpO2)	From pre-injection to 120 minutes post-injection	Monitor for any changes in SpO2
Cardiac Troponin T	pre-injection and 240 minutes post-injection	Monitor for any changes in Cardiac troponin T

Secondary Outcome Measures

Name	Time	Method
Left Ventricular Opacification (LVO)	Image data obtained pre-injection and within 10 minutes post-injection	The percentage of subjects with moderate or complete left ventricular opacification (LVO), defined by an LVO grade of 2 (moderate) or 3 (complete), as assessed by the blinded central reader(s). The percentage of subjects with complete LVO, defined by an LVO grade of 3 (complete), as assessed by the blinded central reader(s)
Left Ventricular Endocardial Border Delineation (LVEBD)	Image data obtained pre-injection and within 10 minutes post-injection	The change from baseline on the left ventricular endocardial border delineation (LVEBD) score, defined using a standard 12-segment model, as assessed by the blinded central reader(s). The left ventricular (LV) endocardium of the 4- or 2- chamber apical views are divided into 6 segments, with 2 basal, mid- and apical segments in each view. 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 (0-24) is obtained by adding the scores from the 6 individual segments in each of the 2 views. The changes from baseline on LVEBD score of subjects with suboptimal LVEBD at baseline, as defined by 2 or more contiguous segments of 6 segments that cannot be visualized reliably in either the apical 4 and/or the 2-chamber view, as assessed by the blinded central reader(s)
Duration of Clinically Useful Contrast	Image data obtained pre-injection and within 10 minutes post-injection	A duration of clinically useful contrast calculated by measuring the time between the disappearance of shadowing effect (useful effect starts) and the time when moderate or full LV enhancement and contrast enhancement are no longer adequate (useful effect ends), as assessed by the blinded central reader(s)