Ultrasound-Assisted Thrombolysis for Heart Attack

(SONOSTEMILYSIS Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alberta

Must be taking: Fibrinolytics

Must not be taking: Anticoagulants, Aspirin

Disqualifiers: Coronary bypass, Cardiogenic shock, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment method for individuals experiencing a severe type of heart attack called STEMI. The researchers aim to determine if ultrasound waves combined with a special contrast agent, Definity® (Perflutren Lipid Microsphere), can safely dissolve clots during emergency heart attack treatment. One group will receive this ultrasound-assisted treatment, while the other will receive the usual care. The trial seeks participants who have had a STEMI heart attack within the last 6 hours and are expected to receive clot-busting drugs. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking heart attack treatments.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking medications that are contraindicated with the study's treatments, such as certain anticoagulants or aspirin, you may need to adjust your medication regimen.

What prior data suggests that ultrasound-assisted thrombolysis is safe for heart attack patients?

Research has shown that sonothrombolysis, a technique using ultrasound to break up blood clots, has been generally safe in past studies. These studies found that patients experienced better blood flow to the heart after a heart attack, reduced heart damage, and improved heart function. While these benefits were observed, the available information did not detail specific side effects.

The trial is in Phase 2, focusing on testing the treatment's safety and effectiveness. This phase indicates some initial safety data from earlier studies, but more information is needed to fully confirm its safety.

Additionally, Definity®, the ultrasound contrast agent used in this study, has already received FDA approval for other uses. This approval suggests that Definity® is generally considered safe when used as directed, although all treatments can have potential risks. Researchers will closely monitor participants to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about ultrasound-assisted thrombolysis for heart attacks because it combines traditional ultrasound imaging with a therapeutic approach known as sonothrombolysis. Unlike typical treatments like clot-busting drugs or stents, this method uses ultrasound waves to enhance the breakdown of clots in the heart. The addition of the ultrasound contrast agent Definity® makes it easier to visualize and target the clot precisely. This approach could potentially speed up recovery and improve outcomes by directly enhancing the effectiveness of clot dissolution.

What evidence suggests that ultrasound-assisted thrombolysis is effective for heart attack?

Research has shown that sonothrombolysis, tested in this trial, can help treat STEMI, a type of heart attack. Studies have found that it reopens blocked blood vessels and reduces heart damage, leading to improved heart function after a heart attack. Some research also found that sonothrombolysis improved blood flow and helped keep blood vessels open. Overall, these findings suggest that sonothrombolysis could be a promising addition to current heart attack treatments. Participants in this trial will receive either sonothrombolysis or standard care with diagnostic myocardial contrast echocardiography using the ultrasound contrast agent Definity®. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for heart attack patients over 30 years old who are receiving clot-dissolving therapy within 6 hours of symptom onset. It's specifically for those with high-risk ECG patterns indicating severe heart attacks. People can't join if they're allergic to ultrasound contrast agents, have a bleeding disorder, major heart shunts, took experimental treatments recently, had prior bypass surgery or are in cardiogenic shock.

Inclusion Criteria

You need to have clear images of your heart from certain angles on an echocardiogram.

My ECG shows significant changes indicating a severe heart attack.

I am older than 30 years.

Exclusion Criteria

You have taken another experimental medication or treatment within the last 30 days before having a heart attack.

I have had coronary bypass surgery in the past.

You have had a bad reaction to the special liquid used for the ultrasound test in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive sonothrombolysis or standard therapy for STEMI within 6 hours of symptom onset

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including serial echocardiography assessments

90 days

Multiple visits (in-person) at Day 1, Day 3, and Day 90

Long-term follow-up

Patient outcomes are followed for 1 year after reperfusion

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Definity®

Trial Overview The SONOSTEMI-LYSIS Trial is testing the combination of Definity® (an ultrasound contrast agent) with High Mechanical Index Ultrasound to see if it's safe and works well when used alongside standard clot-dissolving drugs in treating severe heart attacks.

How Is the Trial Designed?

Group I: Sonothrombolysis Experimental Treatment 1 Intervention

Diagnostic myocardial contrast echocardiography with ultrasound contrast agent 5% Definity® plus Sonothrombolysis

Group II: Standard of Care Active Control 1 Intervention

Diagnostic myocardial contrast echocardiography with ultrasound contrast agent 5% Definity®

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Canadian VIGOUR Centre

Collaborator

Trials

9

Recruited

11,000+

Published Research Related to This Trial

In the first year of using the second-generation contrast agent Definity in echocardiography, 161 patients showed a significant improvement in endocardial definition scores (p=0.0001), enhancing the clarity of heart imaging.

The use of contrast echocardiography led to the detection of clinically significant conditions that were missed in standard 2D imaging, with a very low adverse event rate of only 0.6%, indicating its safety and efficacy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast echocardiography in Australian clinical practice. Hamilton-Craig, C., Boga, T., West, C., et al.[2022]

Using a clinical ultrasound contrast agent (Definity) combined with 220 kHz pulsed ultrasound significantly enhances the effectiveness of rt-PA in dissolving blood clots, as shown in both laboratory and preclinical studies.

In a porcine model of cerebral thromboembolism, this combination treatment accelerated reperfusion by up to 45 minutes compared to rt-PA or saline alone, indicating a promising approach for improving thrombolysis outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model. Kleven, RT., Karani, KB., Hilvert, N., et al.[2023]

In two patients with cardiac tamponade, echocardiographic-guided pericardiocentesis successfully drained bloody fluid, demonstrating the procedure's efficacy in managing this condition.

The use of Definity perflutren lipid microspheres as echocardiographic contrast during the procedure is a novel approach that enhanced the accuracy of needle placement, marking the first reported application of this technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perflutren microspheres for contrast echocardiography in a bloody pericardiocentesis. Escabí-Mendoza, JE., Martínez-Díaz, JD., Avilés-Rivera, ED.[2018]

Echocardiography, while commonly used to assess heart function, can be suboptimal in 15-20% of cases, but using ultrasound microbubble contrast like DEFINITY® significantly improves diagnostic accuracy and helps salvage nondiagnostic studies.

DEFINITY® is an FDA-approved microbubble contrast agent that enhances left ventricular imaging, providing clearer assessments of cardiac function and wall motion abnormalities, with a well-defined safety profile and clinical indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of ultrasound contrast agents in current clinical practice with special focus on DEFINITY® in cardiac imaging. Salih, M., Ali, SM., Jena, N., et al.[2022]

In a study involving 1,060 patients, Definity (perflutren lipid microsphere) was found to be well tolerated, with no deaths or serious adverse events reported during or within 30 minutes after administration.

The overall adverse event rate was 10.8%, with a low drug-related adverse event rate of 3.5%, indicating that most adverse events were mild or moderate, making Definity a safe option for patients with suboptimal echocardiograms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CaRES (Contrast Echocardiography Registry for Safety Surveillance): a prospective multicenter study to evaluate the safety of the ultrasound contrast agent definity in clinical practice. Weiss, RJ., Ahmad, M., Villanueva, F., et al.[2022]

A 73-year-old patient experienced sudden death shortly after receiving a perflutren contrast agent during an echocardiogram, highlighting potential risks associated with its use in patients with severe heart conditions.

Despite the timing of the death, autopsy results did not establish a direct link between the perflutren agent and the fatal event, suggesting that this case may represent a pseudocomplication rather than a direct adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sudden death after intravenous administration of a perflutren contrast agent: a case of pseudocomplication? Mahjoub, H., Roméo, P., Leung, TK., et al.[2014]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30894317/

Sonothrombolysis in ST-Segment Elevation Myocardial ... Sonothrombolysis added to PCI improves recanalization rates and reduces infarct size, resulting in sustained improvements in systolic function after STEMI.

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCIMAGING.119.009536

Sonothrombolysis Improves Myocardial Dynamics and ... The results of this pioneering trial demonstrated that sonothrombolysis improved angiographic recanalization rates, reduced infarct size, and ...

3. jacc.org jacc.org/doi/10.1016/j.jacc.2019.03.006

Sonothrombolysis in ST-Segment Elevation Myocardial ... Sonothrombolysis added to PCI improves recanalization rates and reduces infarct size, resulting in sustained improvements in systolic function after STEMI.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0894731724003493

Sonothrombolysis Before and After Percutaneous ... Sonothrombolysis, delivered before and after primary percutaneous coronary intervention (pPCI), increases infarct vessel patency, improves microvascular flow, ...

5. jscai.org jscai.org/article/S2772-9303(25)00235-2/fulltext

A-43 | Efficacy of Sonothrombolysis as an Adjuvant to PCI ... Sonothrombolysis demonstrated significant efficacy in achieving complete ST-segment resolution (RR 2.69, 95% CI 1.06–6.82) and reducing infarct size in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9511427/

Sono-assisted-thrombolysis by three-dimensional ... Three-dimensional sono-assisted-thrombolysis directly improves infarct-related recanalization rates, enhances microcirculation, reduces r-tPA dosage, and ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/89/NCT03092089/Prot_SAP_000.pdf

Sonothrombolysis in Patients with an ST-segment ... Once completed, this will provide prospective data on the efficacy and safety of sonothrombolysis which we believe will lead to a randomized clinical trial of ...