Back to resultsA Dose Ascending Study to Evaluate the Safety of NH002 as a Contrast Agent in Cardiac Echocardiography
Primary Purpose
Cardiac Disease
Status
Completed
Phase
Phase 1
Locations
Taiwan
Study Type
Interventional
Intervention
NH002 (Perflutren Lipid Microspheres) Injectable Suspension
Echocardiogram
Sponsored by
About this trial
This is an interventional diagnostic trial for Cardiac Disease focused on measuring Echo, Echocardiogram, Cardiac ultrasound, suboptimal, contrast agent, enhancing agent, LVO, LVEBD
Eligibility Criteria
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)
Sites / Locations
- Taipei Mackay Memorial Hospital
- Taipei Veterans General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm
Arm Description
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
Outcomes
Primary Outcome Measures
12-lead ECGs
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
Body temperature
Monitor for any changes in body temperature (in Celsius degree)
Heart rate
Monitor for any changes in heart rate (in beats/min)
Respiratory rate
Monitor for any changes in respiratory rate (in breaths/min)
Blood pressure
Monitor for any changes in blood pressure (in mmHg)
Thrombin time (TT) and Activated partial thromboplastin time (aPTT)
Monitor for any changes in TT and aPTT
Cardiac troponin I
Monitor for any changes in Cardiac troponin I
Oxygen saturation by pulse oximetry (SpO2)
Monitor for any changes in SpO2
Rate of any potential adverse allergic reaction
Monitor for any potential adverse allergic reaction
Secondary Outcome Measures
Left Ventricular Opacification (LVO)
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)
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
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)
Full Information
NCT ID
NCT04185246
First Posted
November 6, 2019
Last Updated
June 30, 2021
Sponsor
Trust Bio-sonics, Inc.
Collaborators
StatPlus,Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04185246
Brief Title
A Dose Ascending Study to Evaluate the Safety of NH002 as a Contrast Agent in Cardiac Echocardiography
Official Title
A Multicenter, Open-Label, Dose Ascending Study to Evaluate the Safety of NH002 as a Contrast Agent in Cardiac Echocardiography
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
November 4, 2019 (Actual)
Primary Completion Date
July 1, 2020 (Actual)
Study Completion Date
July 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Trust Bio-sonics, Inc.
Collaborators
StatPlus,Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Disease
Keywords
Echo, Echocardiogram, Cardiac ultrasound, suboptimal, contrast agent, enhancing agent, LVO, LVEBD
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Masking Description
The reviewer of echocardiograms in this trial is blinded to the treatment assignments and subject identifiers.
Allocation
N/A
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single arm
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
NH002 (Perflutren Lipid Microspheres) Injectable Suspension
Intervention Description
NH002 is formulated as a microbubble injectable suspension for intravenous administration. NH002 requires an activation process prior to use.
Intervention Type
Diagnostic Test
Intervention Name(s)
Echocardiogram
Intervention Description
Each patient will undergo an unenhanced ultrasound examination and a NH002 contrast-enhanced examination on the same day.
Primary Outcome Measure Information:
Title
12-lead ECGs
Description
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
Time Frame
From pre-injection to 60 minutes post injection
Title
Body temperature
Description
Monitor for any changes in body temperature (in Celsius degree)
Time Frame
From pre-injection to 120 minutes post injection
Title
Heart rate
Description
Monitor for any changes in heart rate (in beats/min)
Time Frame
From pre-injection to 120 minutes post injection
Title
Respiratory rate
Description
Monitor for any changes in respiratory rate (in breaths/min)
Time Frame
From pre-injection to 120 minutes post injection
Title
Blood pressure
Description
Monitor for any changes in blood pressure (in mmHg)
Time Frame
From pre-injection to 120 minutes post injection
Title
Thrombin time (TT) and Activated partial thromboplastin time (aPTT)
Description
Monitor for any changes in TT and aPTT
Time Frame
From pre-injection to 240 minutes post-injection
Title
Cardiac troponin I
Description
Monitor for any changes in Cardiac troponin I
Time Frame
pre-injection and 240 minutes post-injection
Title
Oxygen saturation by pulse oximetry (SpO2)
Description
Monitor for any changes in SpO2
Time Frame
From pre-injection to 120 minutes post-injection
Title
Rate of any potential adverse allergic reaction
Description
Monitor for any potential adverse allergic reaction
Time Frame
From pre-injection to 240 minutes post-injection
Secondary Outcome Measure Information:
Title
Left Ventricular Opacification (LVO)
Description
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)
Time Frame
Image data obtained pre-injection and within 10 minutes post-injection
Title
Left Ventricular Endocardial Border Delineation (LVEBD)
Description
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)
Time Frame
Image data obtained pre-injection and within 10 minutes post-injection
Title
Duration of clinically useful contrast
Description
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)
Time Frame
Image data obtained pre-injection and within 10 minutes post-injection
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wen-Chung Yu
Organizational Affiliation
Taipei Veterans General Hospital, Taiwan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Taipei Mackay Memorial Hospital
City
Taipei
ZIP/Postal Code
10449
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Dose Ascending Study to Evaluate the Safety of NH002 as a Contrast Agent in Cardiac Echocardiography
We'll reach out to this number within 24 hrs