Comparing the Safety and Efficacy of ASI-02 to Agitated Saline for Suspected Right-to-left Shunt

Official title

A Phase 3, Open-label, Multicenter, Randomized Crossover Trial Comparing the Safety and Efficacy of ASI-02 to Agitated Saline for Suspected Right-to-left Shunt

Overview

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

• Drug Agitated 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.
• Drug ASI-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.

Primary outcome measures

• Positive percentage agreement (PPA) of ASI-02 for detecting right-to-left shunt versus agitated saline SoC [Time frame: 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 [Time frame: Procedure through 24- to 48-hour participant follow-up visit]

Secondary outcome measures (10)

• The incidence of ASI-02-related adverse events [Time frame: 24- to 48-hour participant follow-up visit]
• Peak opacification intensity [Time frame: Procedure through 24- to 48-hour participant follow-up visit]
• Contrast opacification duration [Time frame: Procedure through 24- to 48-hour participant follow-up visit]
• Positive percentage agreement (PPA) of ASI-02 for shunt detection at rest [Time frame: Procedure through 24- to 48-hour participant follow-up visit]
• Negative percentage agreement (NPA) of ASI-02 for shunt detection at rest [Time frame: Procedure through 24- to 48-hour participant follow-up visit]
• Positive percentage agreement (PPA) of ASI-02 for shunt detection specific to shunt sizes [Time frame: Procedure through 24- to 48-hour participant follow-up visit]
• Negative percentage agreement (NPA) of ASI-02 for shunt detection specific to shunt sizes [Time frame: Procedure through 24- to 48-hour participant follow-up visit]
• Test-retest reliability of agitated saline SoC [Time frame: 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. [Time frame: 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. [Time frame: Procedure through 24- to 48-hour participant follow-up visit]

Eligibility criteria

Inclusion criteria

• Patient is clinically indicated for a saline contrast TTE study with a suspected right-to-left shunt
• Patient must be at least 18 years of age inclusive, at the time of signing the informed consent
• Able to communicate effectively with trial personnel

Exclusion criteria

• 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
• 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
• Allergy to polysorbate 80 (PS-80)
• 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
• 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
• 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)
• Unstable cardiovascular status defined as:

• myocardial infarction or unstable angina pectoris within 6 months prior to procedure day
• symptomatic valvular heart disease or moderate to severe stenotic valvular heart disease
• clinically significant congenital heart defects (excluding an atrial septal defect \[ASD\], patent foramen ovale \[PFO\], or pulmonary arteriovenous malformation \[PAVM\])
• current uncontrolled cardiac arrhythmias causing clinical symptoms requiring medical intervention or hemodynamic compromise
• acute pulmonary embolus or pulmonary infarction
• acute myocarditis or pericarditis
• acute aortic dissection
• untreated atrial fibrillation
• Any major surgery within 30 days prior to screening
• Participation in any investigational drug, device, or placebo study within 30 days prior to screening
• Vulnerable adult participant populations (e.g., incarcerated or cognitively challenged adults)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Diagnostic

Study locations

United States · 7 centers

• Northwestern University — Chicago
• AH Illinois Masonic Center — Chicago
• Mayo Clinic — Rochester
• CentraCare — Saint Cloud
• Jackson Heart Clinic — Jackson
• NYU Langone Health — New York
• Aurora St. Lukes Medical Center — Milwaukee

Canada · 1 center

• Toronto General — Toronto

Identifiers

NCT: NCT06938347 · ASI-CL-0301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗