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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Right-To-Left Shunt
• Intervention / Treatment: Drug: Agitated Saline SoC; Drug: ASI-02

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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Pamela Wolfe; Phone Number: 763-258-7027; Email: pamela@agitatedsolutions.com
• Study Contact Backup: Name: Rebecca Zickert; Phone Number: 612-345-4544; Email: rebecca.zickert@brightresearch.com

Study Locations

• Canada
  • Toronto, Canada, M5G 2C4
    • Recruiting
    • Toronto General
    • Principal Investigator: Wendy Tsang, MD
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Principal Investigator: Akhil Narang, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Sunil Mankad, MD
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Recruiting
      • Jackson Heart Clinic
      • Principal Investigator: William Crowder, MD
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Principal Investigator: Daniel Bamira, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard of Care to ASI-02 TTE Study; Participants will be allocated to a saline contrast echocardiography study with agitated saline SoC, followed by a saline contrast echocardiography study with ASI-02.	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.
Experimental: ASI-02 to Standard of Care TTE Study; Participants will be allocated to a saline contrast echocardiography study with ASI-02, followed by a saline contrast echocardiography study with agitated saline SoC.	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.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Agitated Solutions, Inc.
• Collaborators: Bright Research Partners
• Investigators: Principal Investigator: Akhil Narang, MD, Northwestern Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: April 15, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Echocardiogram; Saline Contrast; Saline Contrast Transthoracic Echocardiogram; Transthoracic Echocardiogram; Agitated Saline Standard of Care; Transpulmonary Shunt
• Additional Relevant MeSH Terms: Aberrant Motor Behavior in Dementia; Neurologic Manifestations; Nervous System Diseases; Behavioral Symptoms; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Psychomotor Agitation
• Other Study ID Numbers: ASI-CL-0301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to the potential risks to participant privacy, the possibility of re-identification, concerns about data misuse for commercial purposes, and the potential harm to participants due to sensitive health information, IPD will not be available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No