Right-To-Left Shunt
Conditions
Keywords
Saline Contrast, Saline Contrast Transthoracic Echocardiogram, Transthoracic Echocardiogram, Agitated Saline Standard of Care, Echocardiogram, Transpulmonary Shunt
Brief summary
This is a phase 3, multicenter, open-label, blinded, crossover trial in which each participant will undergo a randomized sequence of ASI-02 and agitated saline standard of care (SoC) via a saline contrast transthoracic echocardiogram (TTE) study.
Detailed description
The primary objective is to determine the safety of ASI-02 and its agreement with agitated saline SoC for detection of right-to-left shunt in saline contrast studies utilizing TTE in the intended setting of use (opacifying the right heart). The investigation will be conducted in up to 8 investigational sites in the U.S. and Canada. Participants will receive n=2 ASI-02, n=4 agitated saline SoC injections as part of a single-day imaging session, with the overall duration for study participation of 24 to 48 hours.
Interventions
DRUGAgitated Saline SoC
The recommended initial dose of agitated saline SoC is approximately 10 mL of saline containing approximately 1 mL of air, per institutional policy, rapidly mixed (approximately 10-20 presses) to manufacture microbubbles. No additives are allowed to the saline, including blood, dextrose, or bacteriostatic saline.
DRUGASI-02
Each injection shall utilize one (1) ASI-02 product connected to one (1) pre-filled 10 mL 0.9% sodium chloride (saline) syringe. The ASI-02 investigational product will be connected to a standard luer lock connector and administered in its entirety. The intravenous bolus injected dose of ASI-02 is 9 mL of saline and 1 mL of air.
Sponsors
Agitated Solutions, Inc.
Bright Research Partners
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Masking description
This is an open-label study; therefore, blinding procedures are not necessary for site personnel or participants. Blinded assessment of the primary efficacy endpoint will be completed by the core lab.
Intervention model description
For each participant, the first two (2) injections will be agitated saline SoC (one \[1\] injection at rest, one \[1\] injection during a maneuver). Next, participants will be randomized to either receive two (2) ASI-02 injections followed by two (2) agitated saline SoC injections, or vice versa (with each pair involving an injection at rest and an injection during a maneuver).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient is clinically indicated for a saline contrast TTE study with a suspected right-to-left shunt 2. Patient must be at least 18 years of age inclusive, at the time of signing the informed consent 3. Able to communicate effectively with trial personnel
Exclusion criteria
1. Female patients who are pregnant or lactating. All women of child-bearing potential (WOCBP) must have a negative urine pregnancy test at screening regardless of contraceptive use history 2. WOCBP are excluded unless they have been using an adequate and medically approved method of contraception to avoid pregnancy for at least 1 month prior to ASI-02 dose administration 3. Allergy to polysorbate 80 (PS-80) 4. American Society of Anesthesiologists (ASA) physical status classification IV, V, or VI, except that participants with ASA physical status IV due solely to recent suspected transient ischemic attack or cerebrovascular accident are eligible for inclusion 5. Current illness or pathology that in the opinion of the investigator would prevent undergoing investigational product administration due to a significant safety risk to the patient 6. 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) 7. Unstable cardiovascular status defined as: 1. myocardial infarction or unstable angina pectoris within 6 months prior to procedure day 2. symptomatic valvular heart disease or moderate to severe stenotic valvular heart disease 3. clinically significant congenital heart defects (excluding an atrial septal defect \[ASD\], patent foramen ovale \[PFO\], or pulmonary arteriovenous malformation \[PAVM\]) 4. current uncontrolled cardiac arrhythmias causing clinical symptoms requiring medical intervention or hemodynamic compromise 5. acute pulmonary embolus or pulmonary infarction 6. acute myocarditis or pericarditis 7. acute aortic dissection 8. untreated atrial fibrillation 8. Any major surgery within 30 days prior to screening 9. Participation in any investigational drug, device, or placebo study within 30 days prior to screening 10. Vulnerable adult participant populations (e.g., incarcerated or cognitively challenged adults)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Positive percentage agreement (PPA) of ASI-02 for detecting right-to-left shunt versus agitated saline SoC | Procedure through 24- to 48-hour participant follow-up visit |
| Negative percentage agreement (NPA) of ASI-02 for detecting right-to-left shunt versus agitated saline SoC | Procedure through 24- to 48-hour participant follow-up visit |
Secondary
| Measure | Time frame |
|---|---|
| The incidence of ASI-02-related adverse events | 24- to 48-hour participant follow-up visit |
| Peak opacification intensity | Procedure through 24- to 48-hour participant follow-up visit |
| Contrast opacification duration | Procedure through 24- to 48-hour participant follow-up visit |
| Positive percentage agreement (PPA) of ASI-02 for shunt detection at rest | Procedure through 24- to 48-hour participant follow-up visit |
| Negative percentage agreement (NPA) of ASI-02 for shunt detection at rest | Procedure through 24- to 48-hour participant follow-up visit |
| Positive percentage agreement (PPA) of ASI-02 for shunt detection specific to shunt sizes | Procedure through 24- to 48-hour participant follow-up visit |
| Negative percentage agreement (NPA) of ASI-02 for shunt detection specific to shunt sizes | Procedure through 24- to 48-hour participant follow-up visit |
| Test-retest reliability of agitated saline SoC | Procedure through 24- to 48-hour participant follow-up visit |
| Positive percentage agreement (PPA) of ASI-02 for detecting right-to-left shunt versus agitated saline SoC, using the first (nonrandomized) SoC study. | Procedure through 24- to 48-hour participant follow-up visit |
| Negative percentage agreement (NPA) of ASI-02 for detecting right-to-left shunt versus agitated saline SoC, using the first (nonrandomized) SoC study. | Procedure through 24- to 48-hour participant follow-up visit |
Countries
Canada, United States
Contacts
CONTACTPamela Wolfe
CONTACTRebecca Zickert
PRINCIPAL_INVESTIGATORAkhil Narang, MD
Northwestern Medicine
Outcome results
None listed