Catheter-directed Thrombolysis for Pulmonary Embolism

(HI-PEITHO Trial)

Recruiting at67 trial locations

Overseen by Stavros Konstantinides, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial compares two treatments for blood clots in the lungs in patients at higher risk of complications. One treatment uses only blood thinners, while the other combines blood thinners with a device that uses sound waves to break up clots. The goal is to see which treatment is better at reducing serious problems and death.

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 data supports the effectiveness of the treatment for pulmonary embolism?

Research shows that low molecular weight heparins (a type of blood thinner) are effective and safe for treating pulmonary embolism, with fewer bleeding complications compared to traditional unfractionated heparin. They are also easier to administer and do not require frequent dose adjustments, making them a promising option for treating this condition. ^{1 2 3 4 5}

Is catheter-directed thrombolysis for pulmonary embolism generally safe in humans?

Low-molecular-weight heparins, which are used in treating conditions like pulmonary embolism, have been shown to be safe and effective in several studies. They are often preferred over unfractionated heparin due to fewer side effects, such as bleeding, and can be administered without the need for regular monitoring. ^{1 3 6 7 8}

How is the treatment with the EkoSonic Endovascular System and heparin different from other treatments for pulmonary embolism?

The EkoSonic Endovascular System combined with heparin is unique because it uses a catheter-directed approach to deliver medication directly to the clot in the lungs, potentially enhancing the effectiveness of the treatment compared to standard anticoagulation therapies that are administered systemically. ^{2 9 10 11 12}

Research Team

Kenneth Rosenfield, MD

Principal Investigator

Massachusetts General Hospital, Boston, Massachusetts, USA

Stavros Konstantinides, MD

Principal Investigator

University Medical Center Mainz, Mainz, Germany

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• Anticoagulation with heparin (Anticoagulant)
• EkoSonicTM Endovascular System (Thrombolytic Agent)

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.

Participant Groups

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 Canada, Japan, China, Switzerland for the following indications:

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Anticoagulant agents in the management of pulmonary embolism. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Low-molecular-weight heparin in the treatment of pulmonary embolism. [2007]

4. France pubmed.ncbi.nlm.nih.gov

[Role of low molecular weight heparins for treating non-massive pulmonary embolism]. [2016]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic application of subcutaneous low-molecular-weight heparin in acute venous thrombosis. [2018]

6. Italy pubmed.ncbi.nlm.nih.gov

The role of low-molecular-weight heparins in non-ST-segment elevation acute coronary syndromes. [2007]

7. United States pubmed.ncbi.nlm.nih.gov

Low-molecular-weight heparins in the treatment of acute coronary syndromes. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. [2022]

9. France pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Heparin and low-molecular-weight heparin in the treatment of venous thromboembolism. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Treatment of acute pulmonary embolism by a low molecular weight heparin fraction. A preliminary study. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. [2022]