Anticoagulation vs Thrombectomy for Pulmonary Embolism

Recruiting at 23 trial locations

Overseen By Erin Archard

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Penumbra Inc.

Must not be taking: Thrombolytics, Glycoprotein IIb/IIIa

Disqualifiers: Hemodynamic instability, ECMO, CTEPH, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 48 hours

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for individuals with an intermediate-high risk of acute pulmonary embolism (PE), a condition where a blood clot blocks arteries in the lungs. The researchers aim to determine if using blood thinners (anticoagulation) alone is as safe and effective as combining them with mechanical aspiration thrombectomy, a procedure that uses a device to remove the clot. Individuals who have experienced PE symptoms for 14 days or less and have been diagnosed with PE through a specific type of scan may qualify for this trial. As an unphased trial, this study allows patients to contribute to important research that could enhance future treatment options for PE.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on thrombolytic agents or certain other medications, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that anticoagulants, treatments to prevent blood clots, are generally safe and well-tolerated by people with pulmonary embolism (PE). These treatments are widely used and considered safe for many patients.

Studies have shown encouraging safety results for mechanical aspiration thrombectomy. For example, research using the FlowTriever system found it to be safe, with patients experiencing improvements in heart and lung function. However, no randomized trials specifically for this procedure in PE exist, so the data remains limited.

Overall, anticoagulants are a well-understood treatment with a strong safety record. Mechanical thrombectomy is newer, but early studies suggest it is safe and shows some positive outcomes. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pulmonary embolism because they explore different approaches beyond the usual anticoagulation therapy. While anticoagulants alone are a common treatment, the addition of mechanical aspiration thrombectomy with the Indigo® Aspiration System offers a novel combination. This system physically removes clots, which could lead to quicker and potentially more effective results, especially in severe cases. By comparing these methods, researchers hope to determine if combining mechanical removal with anticoagulation offers better outcomes than using anticoagulants alone.

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

Research has shown that blood thinners, known as anticoagulants, are commonly used to treat pulmonary embolism (PE) and help prevent additional blood clots. These medications reduce the blood's tendency to clot. In this trial, one group of participants will receive only anticoagulation treatment.

Another group will receive mechanical aspiration thrombectomy, using tools like the Indigo Aspiration System, in addition to anticoagulants. This method physically removes clots from blood vessels, improving blood flow and potentially speeding recovery. However, this procedure carries risks, such as bleeding. Both treatments offer benefits, and the trial aims to directly compare their effectiveness. ^{2 3 4 5 6}

Who Is on the Research Team?

Rachel P. Rosovsky, MD

Principal Investigator

Massachusetts General Hospital

Robert Lookstein, MD

Principal Investigator

MOUNT SINAI HOSPITAL

Are You a Good Fit for This Trial?

Adults aged 18-80 with recent acute pulmonary embolism confirmed by imaging, showing specific heart strain and elevated heart markers. Candidates must have suitable veins for the procedure and give informed consent. Excluded are those with active cancer, severe blood pressure issues, certain allergies or bleeding disorders, recent major surgery, pregnancy, or other investigational trial participation.

Inclusion Criteria

My veins are suitable for a specific lung artery procedure.

I have a confirmed pulmonary embolism shown by a CT scan.

I have had signs of a pulmonary embolism for 14 days or less.

Exclusion Criteria

I have severe heart or blood pressure problems needing intense support.

Imaging evidence or other evidence that suggests, in the opinion of the Investigator, that catheter-based intervention is not appropriate for the patient

Current participation in another investigational drug or device trial that may confound the results of this trial. Studies requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational studies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either anticoagulation alone or anticoagulation plus mechanical aspiration thrombectomy with the Indigo Aspiration System

48 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of functional outcomes and quality of life

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Anticoagulation
• Mechanical Aspiration Thrombectomy

Trial Overview The study compares two treatments for serious lung clots: standard blood thinners alone versus blood thinners plus a device that physically removes clots (Indigo Aspiration System). The goal is to see which method is safer and more effective.

How Is the Trial Designed?

Group I: Anticoagulation (AC) Active Control 1 Intervention

Subjects will have their pulmonary embolism treated with anticoagulants alone. There will be no procedure for this group.

Group II: Indigo Active Control 1 Intervention

Subjects will have their pulmonary embolism treated with anticoagulants and mechanical aspiration thrombectomy with the Indigo® Aspiration System.

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

Approved in European Union as Anticoagulants for:

• Pulmonary Embolism
• Deep Vein Thrombosis
• Atrial Fibrillation
• Venous Thromboembolism

Approved in United States as Anticoagulants for:

• Pulmonary Embolism
• Deep Vein Thrombosis
• Atrial Fibrillation
• Venous Thromboembolism

Approved in Canada as Anticoagulants for:

• Pulmonary Embolism
• Deep Vein Thrombosis
• Atrial Fibrillation
• Venous Thromboembolism

Approved in Japan as Anticoagulants for:

• Pulmonary Embolism
• Deep Vein Thrombosis
• Atrial Fibrillation
• Venous Thromboembolism

Approved in China as Anticoagulants for:

• Pulmonary Embolism
• Deep Vein Thrombosis
• Atrial Fibrillation
• Venous Thromboembolism

Approved in Switzerland as Anticoagulants for:

• Pulmonary Embolism
• Deep Vein Thrombosis
• Atrial Fibrillation
• Venous Thromboembolism

Who Is Running the Clinical Trial?

Penumbra Inc.

Lead Sponsor

Trials

38

Recruited

10,800+

Published Research Related to This Trial

In a study of 836 patients with acute pulmonary thromboembolism, 38.5% were treated with direct oral anticoagulants (DOACs), primarily rivaroxaban, indicating a growing acceptance of these medications as alternatives to warfarin.

The main reason for choosing DOACs over warfarin was the difficulty in maintaining effective INR levels, and only 4% of patients experienced bleeding, suggesting that DOACs may offer a safer profile in real-life settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency of Direct Oral Anticoagulants Usage in Acute Pulmonary Thromboembolism Treatment in Turkey (TUPEDO). Tanrıverdi, E., Tutar, N., Şentürk, A., et al.[2022]

Maintenance treatment for pulmonary embolism (PE) with novel oral anticoagulants like rivaroxaban, dabigatran, and apixaban is less expensive than traditional warfarin therapy, with average costs of €233.3, €231.7, and €229.6 respectively, compared to €286.5 for warfarin.

For patients with low complication risk who do not require hospitalization, the costs of alternative treatments are significantly lower, with warfarin costing €883.1 compared to €254.3 for rivaroxaban and €238 for apixaban.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cost comparison of warfarin vs enoxaparine or new oral anticoagulants used for the treatment of patients with pulmonary embolism. Türk, M., Aldağ, Y., Oğuzülgen, İK., et al.[2023]

Direct-acting oral anticoagulants (DOACs) like dabigatran, rivaroxaban, apixaban, and edoxaban offer predictable dosing and fewer drug interactions compared to traditional anticoagulants, making them easier to use for preventing and treating blood clots.

However, DOACs can accumulate in patients with kidney issues, lack routine monitoring tests for their effects, and currently have no specific antidotes for reversing their effects in cases of overdose or severe bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives. Gómez-Outes, A., Suárez-Gea, ML., Lecumberri, R., et al.[2022]

In a study of 100 patients with acute pulmonary embolism, apixaban was found to significantly increase the activity of coagulation factors II and VII compared to rivaroxaban and dabigatran, suggesting a stronger effect on the coagulation cascade.

The higher thrombin activity observed in patients taking apixaban may enhance their hemostatic response during treatment, but it could also raise concerns about a potential prothrombotic state if therapy is interrupted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences between activities of coagulation factors after one month of therapy with different direct oral anticoagulant in pulmonary embolism patients. Dzudovic, J., Dzudovic, B., Subota, V., et al.[2019]

In a study of 302 patients with intermediate-high risk pulmonary embolism, those who received direct oral anticoagulants (DOACs) within 72 hours of admission had a lower rate of adverse outcomes (4.8%) compared to those who received DOACs later (9.0%).

The early DOAC group did not experience a higher rate of major bleeding compared to the delayed group, suggesting that early treatment is both safe and potentially beneficial for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early prescription of direct oral anticoagulant for the treatment of intermediate-high risk pulmonary embolism: a multi-center, observational cohort study. Chopard, R., Badoz, M., Eveno, C., et al.[2021]

Direct oral anticoagulants (DOACs) like apixaban, rivaroxaban, and dabigatran have been shown to be effective in treating pulmonary embolism (PE) and have a potentially improved safety profile compared to traditional anticoagulants, based on successful phase III trials.

DOACs provide a simplified and effective alternative for anticoagulation therapy in PE management, allowing clinicians more options to optimize patient care and improve clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute pulmonary embolism: risk assessment, risk stratification and treatment options. Piovella, F., Iosub, DI.[2019]

In a meta-analysis of 18 studies with 41,447 participants, direct oral anticoagulants (DOACs) were found to significantly reduce the incidence of all bleeding events, major bleeding, and all-cause death in patients with liver disease compared to warfarin or low molecular weight heparin (LMWH).

Specifically, DOACs reduced the risk of gastrointestinal bleeding and intracranial hemorrhage, particularly in patients with mild to moderate cirrhosis, indicating a safer profile for anticoagulation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of direct oral anticoagulants in patients with liver disease: a systematic review and meta-analysis. Zhao, Y., Zhu, L., Yang, Y., et al.[2023]

A network meta-analysis of three trials found that there were no significant differences in the risk of recurrent venous thromboembolism (VTE), major bleeding, or all-cause mortality among the new oral anticoagulants (NOACs) dabigatran, rivaroxaban, and apixaban.

Apixaban 2.5 mg twice daily was associated with significantly less clinically relevant non-major bleeding compared to rivaroxaban 20 mg daily and dabigatran 150 mg BID, suggesting it may be a safer option for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabigatran, rivaroxaban and apixaban for extended venous thromboembolism treatment: network meta-analysis. Alotaibi, G., Alsaleh, K., Wu, C., et al.[2015]

The four direct oral anticoagulants (DOACs) - apixaban, edoxaban, rivaroxaban, and dabigatran - demonstrated noninferiority to standard therapy in treating deep vein thrombosis and pulmonary embolism, as well as in preventing recurrent venous thromboembolism, based on large phase III studies.

DOACs showed a similar safety profile to standard therapy, with some studies indicating a significantly reduced risk of major bleeding, highlighting their potential advantages in certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct Oral Anticoagulants and Their Use in Treatment and Secondary Prevention of Acute Symptomatic Venous Thromboembolism. Granziera, S., Hasan, A., Cohen, AA.[2016]

Patients with pulmonary embolism treated with rivaroxaban mono-therapy had a significantly shorter hospital stay (9.29 days) compared to those receiving standard therapy with enoxaparin and vitamin K antagonists (11.38 days).

The rivaroxaban group experienced significantly fewer mild hemorrhages (16.7%) compared to the standard therapy group (50%) after one month, indicating a better safety profile for rivaroxaban in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of rivaroxaban mono-therapy and standard-therapy adjusted by CYP2C9 and VKORC1 genotypes in symptomatic pulmonary embolism. Duan, L., Zhang, N., Yan, H., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11887559/

Results From the Prospective APEX-AV Trial - PMC This study evaluated the safety and efficacy of percutaneous mechanical aspiration thrombectomy with the AlphaVac F18 85 System (AngioDynamics) in patients ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772930325011032?via%3Dihub

Novel Aspiration Thrombectomy and Blood Reinfusion ... This study confirms that thrombectomy and autologous blood reinfusion with the AVENTUS Thrombectomy System is a safe and effective primary treatment option in ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36373768/

Mechanical aspiration thrombectomy for the treatment of ... There are no randomized trials studying the outcomes of mechanical aspiration thrombectomy (MAT) for management of pulmonary embolism (PE).

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0146280624000598

A meta-analysis of outcomes of aspiration thrombectomy ... Aspiration thrombectomy has success rates in both high-risk and intermediate-risk PE, however, procedural risks, including bleeding, must be anticipated.

5. eurointervention.pcronline.com eurointervention.pcronline.com/article/acute-outcomes-for-the-full-us-cohort-of-the-flash-mechanical-thrombectomy-registry-in-pulmonary-embolism

Acute outcomes for the full US cohort of the FLASH ... Conclusions: Mechanical thrombectomy with the FlowTriever System demonstrates a favourable safety profile, improvements in haemodynamics and functional outcomes ...

6. americanjir.com americanjir.com/safety-and-outcomes-with-use-of-flowtriever-for-mechanical-thrombectomy-i-n-acute-pulmonary-embolism/

Safety and outcomes with use of FlowTriever for ... We present a descriptive analysis of outcomes including improved mortality, and functional assessment of patients undergoing CDMT.