Anticoagulation vs Thrombectomy for Pulmonary Embolism

Recruiting at 19 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

Trial Summary

What is the purpose of this trial?

The primary objective of this trial is to evaluate the safety and efficacy of treatment with anticoagulation alone versus anticoagulation and mechanical aspiration thrombectomy with the Indigo Aspiration System for the treatment of intermediate-high risk acute pulmonary embolism (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.

What data supports the effectiveness of anticoagulants for treating pulmonary embolism?

Research shows that direct oral anticoagulants (DOACs) like apixaban, rivaroxaban, and dabigatran are effective for treating pulmonary embolism and preventing its recurrence. They are as effective as traditional treatments like warfarin, with some studies indicating a lower risk of major bleeding. ^{1 2 3 4 5}

Is anticoagulation generally safe for humans?

Direct oral anticoagulants (DOACs) like apixaban, rivaroxaban, and dabigatran are generally considered safe for treating blood clots, but they can accumulate in people with kidney problems and lack specific antidotes for overdose. They have fewer drug interactions and don't require injections, but monitoring their effects can be challenging. ^{1 3 6 7 8}

How do anticoagulant drugs differ from other treatments for pulmonary embolism?

Anticoagulant drugs, especially direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, and dabigatran, offer a more convenient alternative to traditional treatments by eliminating the need for regular blood monitoring and dietary restrictions associated with warfarin. They work by directly inhibiting specific factors in the blood clotting process, which can reduce the risk of bleeding compared to older therapies. ^{1 2 5 9 10}

Research Team

Rachel P. Rosovsky, MD

Principal Investigator

Massachusetts General Hospital

Robert Lookstein, MD

Principal Investigator

MOUNT SINAI HOSPITAL

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Acute pulmonary embolism: risk assessment, risk stratification and treatment options. [2019]

3. United States 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. [2021]

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

Direct Oral Anticoagulants and Their Use in Treatment and Secondary Prevention of Acute Symptomatic Venous Thromboembolism. [2016]

5. Turkey pubmed.ncbi.nlm.nih.gov

Frequency of Direct Oral Anticoagulants Usage in Acute Pulmonary Thromboembolism Treatment in Turkey (TUPEDO). [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety of direct oral anticoagulants in patients with liver disease: a systematic review and meta-analysis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Dabigatran, rivaroxaban and apixaban for extended venous thromboembolism treatment: network meta-analysis. [2015]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of rivaroxaban mono-therapy and standard-therapy adjusted by CYP2C9 and VKORC1 genotypes in symptomatic pulmonary embolism. [2017]

10. Turkey 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. [2023]