Catheter-directed Thrombolysis for Pulmonary Embolism

(HI-PEITHO Trial)

Not currently recruiting at 78 trial locations

Overseen By Megan White

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Boston Scientific Corporation

Must be taking: Blood thinners

Must not be taking: Antiplatelets, Anticoagulants, Thrombolytics

Disqualifiers: Hemodynamic instability, Active bleeding, Stroke, 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

Compensation: Varies

Number of Visits: 4

Duration: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best treatment for pulmonary embolism (PE), a condition where blood clots block blood flow in the lungs. It compares two treatments: using only blood thinners (anticoagulation with heparin) and combining blood thinners with a device that helps break down clots (EkoSonicTM Endovascular System). The goal is to determine which method better reduces the risk of death and other serious complications. Individuals recently diagnosed with a PE and at risk of serious complications may be suitable for this trial. Researchers will closely monitor participants for a year to gather important health information. As a Phase 4 trial, this research involves an FDA-approved treatment, aiming to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain blood thinners and antiplatelet medications before participating. If you are on medications like apixaban, rivaroxaban, dabigatran, edoxaban, or certain antiplatelet agents, you may need to stop them before joining the study.

What is the safety track record for these treatments?

Previous studies have shown that the EkoSonic Endovascular System is safe for treating pulmonary embolism (PE), a condition where blood clots block the arteries in the lungs. Research indicates that this system, which uses sound waves to break up blood clots, is well-tolerated. It carries a lower risk of bleeding and helps improve heart function over time. Users of this device also report a better quality of life afterward.

The anticoagulation treatment, involving blood thinners like heparin, is already widely used and FDA-approved for treating blood clots, suggesting it is generally safe and well-tolerated for most people.

Overall, both treatment options in this trial have a history of safety in human use. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the catheter-directed thrombolysis treatment for pulmonary embolism because it combines anticoagulation with a unique delivery method using the EkoSonicTM Endovascular System. Unlike standard treatments like heparin alone, this system uses ultrasound to facilitate the targeted delivery of thrombolytics directly to the clot. This approach not only aims to enhance the effectiveness of clot breakdown but also potentially reduces the risk of bleeding compared to systemic thrombolysis. By delivering medication directly to the problem area, researchers hope this method will offer faster and more efficient relief from pulmonary embolism symptoms.

What evidence suggests that this trial's treatments could be effective for pulmonary embolism?

Research has shown that both treatments in this trial effectively treat pulmonary embolism (PE). Participants in one arm of the trial will receive anticoagulation with heparin, commonly used to prevent clots from enlarging or new ones from forming. Another arm will receive the EkoSonic Endovascular System combined with blood thinners. The EkoSonic system uses sound waves to break down clots more quickly. Studies have found that this combination can improve heart health over time and reduce the risk of serious complications. The EkoSonic treatment is also associated with low mortality rates and improved quality of life. Both treatments are safe and have been successfully used in many patients with PE. ^{1 2 3 6 7}

Who Is on the Research Team?

Stavros Konstantinides, MD

Principal Investigator

University Medical Center Mainz, Mainz, Germany

Kenneth Rosenfield, MD

Principal Investigator

Massachusetts General Hospital, Boston, Massachusetts, USA

Are You a Good Fit for This Trial?

Adults aged 18-80 with a recent diagnosis of acute pulmonary embolism, at elevated risk of early death or hemodynamic collapse, but not in shock or needing intensive care for other reasons. They must have certain clinical signs like increased heart rate and specific blood test results. Excluded are those who've had major bleeding issues, strokes, certain surgeries recently, severe infections like COVID-19 if it's not the main issue, pregnant women, and people on some chronic medications.

Inclusion Criteria

Your right-to-left ventricular diameter ratio is 1.0 or higher on a specific type of imaging test called a CTPA.

I am at high risk of early death or severe health decline due to new health issues.

Your blood test shows high levels of troponin I or T.

Exclusion Criteria

I haven't had major surgery or serious injury in the last 3 weeks.

I have been treated with dabigatran or edoxaban for my PE without first receiving heparin for 5 days.

I have had bleeding in my brain or eyes at some point.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either anticoagulation alone or anticoagulation with the EkoSonicTM Endovascular device for thrombolysis

7 days

In-hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment with assessments at 7 days, 30 days, 6 months, and 12 months

12 months

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Anticoagulation with heparin
• EkoSonicTM Endovascular System

Trial Overview The HI-PEITHO study is testing two treatments for pulmonary embolism: standard anticoagulation therapy alone versus anticoagulation plus the EkoSonicTM Endovascular System to break up clots. Participants will be randomly assigned to one of these treatments and monitored over a year through several follow-ups to see which treatment reduces death and complications more effectively.

How Is the Trial Designed?

Group I: Anticoagulation and EkoSonicTM Endovascular System Active Control 2 Interventions

Low-molecular weight heparin (LMWH) or unfractionated heparin (UFH) and EkoSonicTM Endovascular System \[ultrasound-facilitated catheter-directed delivery of thrombolytic: 2 mg bolus/catheter + 1 mg/hour/catheter for 7 hours (total of 9 or 18 mg\]

Group II: Anticoagulation Active Control 1 Intervention

Low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)

Anticoagulation with heparin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Heparin for:

• Venous thromboembolism
• Pulmonary embolism
• Deep vein thrombosis
• Acute coronary syndrome

Approved in United States as Heparin for:

• Venous thromboembolism
• Pulmonary embolism
• Deep vein thrombosis
• Acute coronary syndrome

Approved in Canada as Heparin for:

• Venous thromboembolism
• Pulmonary embolism
• Deep vein thrombosis
• Acute coronary syndrome

Approved in Japan as Heparin for:

• Venous thromboembolism
• Pulmonary embolism
• Deep vein thrombosis
• Acute coronary syndrome

Approved in China as Heparin for:

• Venous thromboembolism
• Pulmonary embolism
• Deep vein thrombosis
• Acute coronary syndrome

Approved in Switzerland as Heparin for:

• Venous thromboembolism
• Pulmonary embolism
• Deep vein thrombosis
• Acute coronary syndrome

Who Is Running the Clinical Trial?

Boston Scientific Corporation

Lead Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

University Medical Center Mainz

Collaborator

Trials

26

Recruited

44,600+

National PERT Consortium, Inc.

Collaborator

Trials

1

Recruited

540+

Published Research Related to This Trial

Unfractionated heparin is the preferred anticoagulant for preventing pulmonary embolism in low to moderate risk patients, while high-risk patients benefit more from low molecular weight heparins (LMWHs) or oral anticoagulants.

Although unfractionated heparin is effective, it has limitations due to its variable anticoagulant effect caused by aspecific binding to plasma proteins; newer agents like LMWHs and selective thrombin inhibitors show promise in overcoming these issues and are being evaluated in ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticoagulant agents in the management of pulmonary embolism. Agnelli, G., Sonaglia, F.[2019]

In patients with submassive pulmonary embolism, pulmonary revascularization can be achieved within 14 days in 50% of cases treated with intravenous heparin followed by oral anticoagulants, with a low recurrence rate of 5%.

Low-molecular weight heparins, such as calcium nadroparin and sodium dalteparin, show comparable efficacy to unfractionated heparin for treating submassive pulmonary embolism, with no severe hemorrhage reported in patients treated with low-molecular weight heparins, suggesting they may be a safer and more effective option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of low molecular weight heparins for treating non-massive pulmonary embolism]. Charbonnier, B., Pacouret, G.[2016]

Low molecular weight heparin is more effective and safer than unfractionated heparin in the initial treatment of venous thromboembolism, showing lower risks of recurrence, major bleeding, and mortality based on a review of randomized trials.

The presence of cancer patients in the studies influenced the incidence of recurrent venous thromboembolism and mortality, but it did not affect the overall treatment efficacy of low molecular weight heparin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism. Hettiarachchi, RJ., Prins, MH., Lensing, AW., et al.[2019]

Tinzaparin, a low-molecular-weight heparin, is approved in France for treating pulmonary embolism and offers the convenience of daily subcutaneous injections compared to the standard intravenous unfractionated heparin.

A comparative trial involving 612 patients showed that tinzaparin does not provide advantages in overall mortality or bleeding incidence compared to unfractionated heparin, indicating that while it is easier to administer, it may not be more effective in critical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tinzaparin: new indication. Easier treatment of less severe pulmonary embolism. [2007]

In a pilot study involving nine patients with acute pulmonary embolism, the low molecular weight heparin (LMWH) fraction PK 10169 demonstrated effective antithrombotic efficacy, leading to clinical improvement and progressive reperfusion without any recurrence of pulmonary embolism.

The treatment was well-tolerated, showing no significant hemorrhagic side effects, even in patients considered at high risk for bleeding, indicating a favorable safety profile for PK 10169.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of acute pulmonary embolism by a low molecular weight heparin fraction. A preliminary study. Huet, Y., Gouault-Heilmann, M., Contant, G., et al.[2019]

Low-molecular-weight heparins (LMWH) have been shown to be as safe and effective as unfractionated heparin for treating patients with clinically stable pulmonary embolism, based on results from significant clinical trials like Columbus and Thésée.

The convenience of LMWH, which can be administered subcutaneously in fixed doses without the need for laboratory monitoring, allows for the possibility of home treatment for approximately 80% of patients with deep vein thrombosis, indicating a shift towards outpatient management for selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-molecular-weight heparin in the treatment of pulmonary embolism. Ageno, W., Turpie, AG.[2007]

In a study of 2213 patients with acute pulmonary embolism, fondaparinux was found to be at least as effective as unfractionated heparin, with a lower incidence of recurrent thromboembolic events (3.8% vs. 5.0%).

Fondaparinux can be administered subcutaneously once daily without the need for laboratory monitoring, making it a safer and more convenient option for treating hemodynamically stable patients compared to the intravenous administration of unfractionated heparin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. Büller, HR., Davidson, BL., Decousus, H., et al.[2022]

Low molecular weight heparins (LMWHs) like enoxaparin have been shown to result in fewer adverse events compared to unfractionated heparin in patients with acute coronary syndromes, based on findings from two large studies.

LMWHs can be safely combined with platelet glycoprotein IIb/IIIa inhibitors, suggesting their versatility and potential for enhanced treatment strategies in acute coronary syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of low-molecular-weight heparins in non-ST-segment elevation acute coronary syndromes. Nguyen-Ho, P., Levine, GN.[2007]

In a study of 50 patients with acute deep-vein thrombosis, low-molecular-weight (LMW) heparin was found to be as effective as unfractionated heparin in improving venous reperfusion, with 70% and 75% success rates respectively.

Both treatments had similar safety profiles, with only a few bleeding complications reported; however, LMW heparin resulted in higher anti-Xa levels and increased protein C and antithrombin III at the end of the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic application of subcutaneous low-molecular-weight heparin in acute venous thrombosis. Harenberg, J., Huck, K., Bratsch, H., et al.[2018]

Low-molecular-weight heparins, like enoxaparin sodium, provide significant advantages over unfractionated heparin in treating acute coronary syndromes, including higher bioavailability and easier administration, which can improve patient compliance.

Enoxaparin sodium has been specifically shown to reduce the risk of coronary events in patients with non-ST segment elevation acute coronary ischemia, highlighting its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-molecular-weight heparins in the treatment of acute coronary syndromes. Turpie, AG., Antman, EM.[2019]

In a study involving 900 patients with symptomatic lower-extremity deep venous thrombosis, subcutaneous enoxaparin administered once or twice daily was found to be as effective as intravenous unfractionated heparin in preventing recurrent venous thromboembolism.

The safety profile was similar across all treatment groups, with no significant differences in the incidence of major hemorrhage, indicating that enoxaparin is a safe alternative to unfractionated heparin for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Merli, G., Spiro, TE., Olsson, CG., et al.[2022]

Low-molecular-weight heparins (LMWH) have become the preferred treatment for venous thromboembolism (VTE) due to their safety and efficacy, showing lower rates of major bleeding and complications compared to unfractionated heparin, based on numerous clinical trials.

LMWH allows for once-daily subcutaneous injections without the need for frequent laboratory monitoring, making it a more convenient option for patients while effectively reducing the risk of recurrent thromboembolism and death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heparin and low-molecular-weight heparin in the treatment of venous thromboembolism. Pineo, GF., Hull, RD.[2019]

Citations

1. bostonscientific.com bostonscientific.com/us/en/healthcare-professionals/products/thrombectomy-systems/ekos-endovascular-system/fp00000423.html

EKOS™ Endovascular System A first-line pulmonary embolism intervention. Proven to yield safe and effective results, EKOS is low risk and reliable. Because of EKOS' small size, ...

2. jscai.org jscai.org/article/S2772-9303(25)01154-8/fulltext

The EKOS-PE Study The EKOS therapy is associated with significant long-term improvement in RV function, low mortality, and favorable perceived QoL, supporting its use in massive ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12462068/

The EKOS-PE Study - PMC - PubMed Central The EKOS therapy is associated with significant long-term improvement in RV function, low mortality, and favorable perceived QoL, supporting its use in massive ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39712851/?utm_source=FeedFetcher&utm_medium=rss&utm_campaign=None&utm_content=0LWBQLUUYwMXNT9zSsoIXhYCdeXJSPLANoBtSvQlE_x&fc=None&ff=20241225232938&v=2.18.0.post9+e462414

Efficacy and Safety of Systemic Thrombolysis and Catheter ... This narrative review aims to explore the efficacy and safety of systemic thrombolysis and CDT in pulmonary embolism.

5. journal.chestnet.org journal.chestnet.org/article/S0012-3692(22)01989-4/fulltext

EKOSONIC ENDOVASCULAR SYSTEM CATHETER FOR ... EKOS catheters, however, are well studied for the treatment of PE alone, and have demonstrated reduced bleeding risk and improved quality of ...

6. ahajournals.org ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.123.013448

Prospective Multicenter International Registry of ... A multicenter international registry designed to study the treatment of acute PE with USCDT, with focus on safety outcomes.

7. evtoday.com evtoday.com/articles/2023-sept/treating-pulmonary-embolism-with-the-ekos-endovascular-system-a-clinicians-perspective

Treating Pulmonary Embolism With the EKOS ... The EKOS system uses ultrasound energy to accelerate dispersion of clot-busting lytic agents deep into the thromboembolism.