Catheter-Directed Therapy for Pulmonary Embolism

(PE-TRACT Trial)

Recruiting at 48 trial locations

Overseen By Stephanie Boumakis

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NYU Langone Health

Must not be taking: Heparin

Disqualifiers: Pregnancy, Low blood pressure, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 7 days

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for submassive pulmonary embolism (PE), where a blood clot blocks lung blood flow and strains the heart. One group will receive catheter-directed therapy (using a thin tube to remove or break down the clot) along with standard blood thinners, while another group will receive only blood thinners (anticoagulant therapy). The goal is to determine if the catheter method improves recovery compared to blood thinners alone. Eligible participants have a recent PE confirmed by a CT scan with right heart strain (right ventricular dilation). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have an allergy to heparin or a history of Heparin-Induced Thrombocytopenia (HIT), 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 catheter-directed therapy (CDT) for treating pulmonary embolism (PE) is generally safe and effective. CDT uses special tools to break up blood clots in the lungs, often improving heart function and reducing lung pressure. Importantly, these benefits come with low rates of serious side effects, such as bleeding or in-hospital deaths.

When comparing treatments, other research has found that CDT is especially safe and effective compared to just taking blood thinners, like anticoagulation. Most patients tolerate CDT well and see improvements quickly.

Overall, evidence suggests that CDT is a well-tolerated option with a strong safety record for those dealing with certain types of PE. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores catheter-directed therapy (CDT) for pulmonary embolism, which could offer a quicker and more targeted approach. Unlike standard anticoagulant therapy that works systemically, CDT directly addresses the clot using mechanical thrombectomy or catheter-directed thrombolysis, potentially leading to faster clot resolution. This method allows for the use of FDA-cleared devices to physically or chemically break down the clot right at its location, which could reduce the risk of complications and improve recovery times. Such direct intervention might offer more immediate relief for patients compared to traditional methods that rely solely on medication.

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

Research has shown that catheter-directed therapy (CDT) can effectively treat pulmonary embolism (PE). In this trial, one group of participants will receive CDT combined with anticoagulant therapy. Studies have found that CDT, especially when used with ultrasound, can significantly lower lung pressure and reduce heart strain. Patients receiving CDT often experience less stress on the right side of the heart, a common issue in PE. However, CDT carries a higher risk of bleeding and death compared to using only blood thinners, which is the treatment for participants in the no-CDT arm of this trial. Despite these risks, CDT often proves very successful, particularly in severe cases of PE. ^{1 2 6 7 8}

Who Is on the Research Team?

Sunil Rao, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for adults with a type of lung blockage called submassive pulmonary embolism, who have certain heart measurements on a CT scan. They must be able to walk independently before the current episode and not have severe kidney issues, allergies to specific clot-dissolving drugs or contrast agents, very low blood counts, or be pregnant.

Inclusion Criteria

I have a blood clot in my lung confirmed by a CT scan.

Your right ventricle is too big compared to your left ventricle, as seen on a CT scan.

Exclusion Criteria

You are pregnant, or could be pregnant, based on a recent test.

I am not allergic to rt-PA or iodinated contrast, or I can take steroids for mild-moderate contrast allergies.

Your blood clotting test shows a high level that cannot be reversed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either catheter-directed therapy (CDT) plus anticoagulation or anticoagulation alone for pulmonary embolism

Up to 7 days

In-hospital treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of peak oxygen consumption and NYHA functional classification

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Anticoagulant Therapy
• Catheter-Directed Therapy

Trial Overview The PE-TRACT study is testing if using catheter-directed therapy (CDT) along with standard blood thinners helps more than just blood thinners alone in patients with a serious lung blockage condition. Participants are randomly chosen to receive either both treatments or only the blood thinner.

How Is the Trial Designed?

Group I: Catheter-Directed Therapy (CDT) plus Anticoagulation Experimental Treatment 2 Interventions

Participants will receive CDT consisting of mechanical thrombectomy (MT) or intrathrombus catheter-directed thrombolysis (CDL) using FDA-cleared devices for pulmonary embolism (PE). The exact technique and devices used will be at the discretion of the endovascular physician, within parameters defined by the PE-TRACT Manual of Operations (MOP) and accepted standard care. Before and after CDT, patients will receive standard PE therapy as in the no-CDT Arm.

Group II: No Catheter-Directed Therapy (No-CDT) Active Control 1 Intervention

Standard anticoagulant therapy (FDA-approved regimen) for the treatment of PE.

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

Approved in European Union as Various Anticoagulants for:

• Venous thromboembolism (VTE)
• Non-valvular atrial fibrillation (NVAF)
• Pulmonary embolism
• Deep vein thrombosis

Approved in United States as Various Anticoagulants for:

• Venous thromboembolism (VTE)
• Non-valvular atrial fibrillation (NVAF)
• Pulmonary embolism
• Deep vein thrombosis

Approved in Canada as Various Anticoagulants for:

• Venous thromboembolism (VTE)
• Non-valvular atrial fibrillation (NVAF)
• Pulmonary embolism
• Deep vein thrombosis

Approved in Japan as Various Anticoagulants for:

• Venous thromboembolism (VTE)
• Non-valvular atrial fibrillation (NVAF)
• Pulmonary embolism
• Deep vein thrombosis

Approved in China as Various Anticoagulants for:

• Venous thromboembolism (VTE)
• Non-valvular atrial fibrillation (NVAF)
• Pulmonary embolism
• Deep vein thrombosis

Approved in Switzerland as Various Anticoagulants for:

• Venous thromboembolism (VTE)
• Non-valvular atrial fibrillation (NVAF)
• Pulmonary embolism
• Deep vein thrombosis

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In critically ill patients with pulmonary embolism, assessing heart chamber size and biomarkers can help identify higher-risk individuals and guide treatment decisions, emphasizing the importance of careful management of right ventricular function.

While anticoagulant therapy is crucial, it should be administered intravenously, and bleeding complications should be monitored closely; various antidotes are available to manage bleeding without necessarily stopping anticoagulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary embolism in the critically ill. Carlbom, DJ., Davidson, BL.[2007]

Heparin and warfarin are effective anticoagulants for treating venous thromboembolic disease, with heparin providing immediate effects and warfarin offering delayed effects, but both carry a risk of hemorrhagic complications.

Thrombolytic therapy is beneficial for patients with massive pulmonary embolism and certain deep venous thrombosis cases, as it helps preserve lung function and reduce postthrombotic syndrome, especially when clinical guidelines are followed to minimize bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of venous thromboembolic disease. A pragmatic approach to anticoagulation and thrombolysis. Linn, BJ., Mazza, JJ., Friedenberg, WR.[2019]

In a study of 326 hospitalized patients with pulmonary embolism, 15% experienced hemorrhagic complications, with the majority being minor events that lasted around 3 days.

Nadroparin, a type of low molecular weight heparin, was associated with 83.3% of major hemorrhagic events, although no fatalities occurred among the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Hemorrhagic Complications in Hospitalized Patients with Pulmonary Embolism. Pagkratis, N., Matsagas, M., Malli, F., et al.[2022]

Catheter-directed therapy (CDT) significantly reduced in-hospital mortality compared to systemic thrombolysis (ST), anticoagulation (AC), and surgical embolectomy (SE) in patients with intermediate to high-risk pulmonary embolism, based on a network meta-analysis of 11 RCTs and 42 observational studies involving 157,454 patients.

CDT also showed a lower rate of recurrent pulmonary embolism compared to ST and AC, while presenting a lower risk of major bleeding compared to ST and AC, indicating it may be a safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of interventions for intermediate to high-risk pulmonary embolism: A network meta-analysis. Ishisaka, Y., Watanabe, A., Fujisaki, T., et al.[2023]

Right ventricular dysfunction is a critical factor in determining the prognosis of patients with pulmonary embolism (PE), influencing treatment strategies based on the severity of the condition.

Non-vitamin K-dependent oral anticoagulants, such as rivaroxaban and apixaban, offer a safer and more straightforward approach to anticoagulation in PE, reducing the risk of major bleeding compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk-adapted management of pulmonary embolism. Barco, S., Konstantinides, SV.[2022]

Anticoagulant therapy, particularly intravenous heparin, has been proven to significantly reduce mortality from pulmonary embolism, dropping rates from 25% to 6%, and remains the standard treatment protocol.

Current treatments, including heparin and oral vitamin K antagonists, show a low recurrence rate of about 5% and a very low incidence of severe bleeding complications (3-5%), indicating both efficacy and safety in managing thromboembolic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anticoagulant therapy in pulmonary embolism]. Charbonnier, B., Pacouret, G., Augusseau-Richard, MP., et al.[2017]

Catheter-directed therapy (CDT) is an effective treatment option for patients with life-threatening submassive pulmonary embolism (PE) who do not respond adequately to anticoagulation or systemic thrombolysis.

In this case, a patient with severe PE and significant right ventricular dysfunction showed marked improvement after receiving CDT, highlighting its potential as a critical intervention in severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catheter-directed therapy for submassive pulmonary embolism after unsuccessful systemic thrombolysis. Dong, C., Jiang, S., Ji, D., et al.[2020]

In a study of 145 patients with acute pulmonary embolism treated with catheter directed therapies (CDT) from 2017 to 2022, those using dedicated CDT devices had a significantly lower in-hospital mortality rate (5%) compared to those treated with pigtail catheters (20%).

The overall mortality rate was higher in patients with high-risk pulmonary embolism (18%) compared to those with intermediate-high risk (5.3%), indicating that risk stratification is crucial in managing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial results of investigator initiated international database on catheter directed therapy of acute pulmonary embolism. Jermakow, MT., Obradovic, S., Salinas, P., et al.[2023]

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 253 patients with acute pulmonary embolism, catheter-directed therapy (CDT) showed a high success rate of 90.9%, particularly effective in patients with intermediate-high risk (IHR) compared to high-risk (HR) patients.

Despite the high success rate of CDT, in-hospital mortality was significantly higher in HR-PE patients at 37.6%, while it was only 2.5% in IHR-PE patients, highlighting the need for improved strategies for managing high-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catheter-directed therapy for acute pulmonary embolism: results of a multicenter national registry. Salinas, P., Vázquez-Álvarez, ME., Salvatella, N., et al.[2023]

In a study of 43,252 cancer-free patients with venous thromboembolism, apixaban was found to have a significantly lower major bleeding risk compared to warfarin and rivaroxaban during the initial treatment phase.

During extended treatment, apixaban and rivaroxaban had similar bleeding risks, both lower than that of warfarin, indicating that apixaban may be a safer long-term option for anticoagulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of type of oral anticoagulation with risk of bleeding in 45,114 patients with venous thromboembolism during initial and extended treatment-A nationwide register-based study. Glise Sandblad, K., Schulman, S., Rosengren, A., et al.[2023]

Acute pulmonary embolism (PE) is a serious condition affecting over 100,000 people annually in the U.S., and while standard treatment involves anticoagulation, some patients require more advanced interventions due to severe symptoms.

Recent advancements in catheter-based therapies, such as catheter-directed thrombolysis and suction thrombectomy, offer targeted treatment options that can improve outcomes for patients with acute PE, emphasizing the importance of a multidisciplinary approach in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contemporary Management of Acute Pulmonary Embolism: Evolution of Catheter-based Therapy. Carlon, TA., Goldman, DT., Marinelli, BS., et al.[2022]

New oral anticoagulants (NOACs) like apixaban, dabigatran, and rivaroxaban offer significant advantages over traditional vitamin-K antagonists for treating pulmonary embolism, including better pharmacokinetics and predictable responses without the need for regular monitoring.

The paper reviews existing literature and ongoing clinical trials to evaluate the efficacy and safety of NOACs, highlighting their potential benefits and drawbacks in managing venous thromboembolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New oral anticoagulants in the treatment of pulmonary embolism: efficacy, bleeding risk, and monitoring. Rudd, KM., Phillips, EL.[2023]

Thrombolytic therapy significantly reduces the risk of recurrent pulmonary embolism or death compared to anticoagulant therapy (5.87% vs 1.94%), based on a meta-analysis of 15 trials involving 1,247 subjects.

While thrombolysis increases the risk of non-major bleeding (12.78% vs 3.65%), it does not significantly increase the risk of major bleeding (3.57% vs 2.67%), indicating a favorable safety profile in terms of severe complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thrombolysis versus anticoagulation for the initial treatment of moderate pulmonary embolism: a meta-analysis of randomized controlled trials. Chen, H., Ren, C., Chen, H.[2014]

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.039096

Revisiting Ultrasound‐Assisted Catheter‐Directed ... Catheter‐directed thrombolysis has historically been a primary treatment for intermediate‐high‐ and high‐risk pulmonary embolism (PE), ...

2. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.035916

Clinical Outcomes in Patients With Acute Pulmonary ... Clinical Outcomes in Patients With Acute Pulmonary Embolism Undergoing Ultrasound‐Assisted Catheter‐Directed Thrombolysis. Dominik F. Draxler, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12151113/

Ultrasound-Assisted Catheter-Directed Thrombolytic Therapy ... The aim of this study was to evaluate the effectiveness and safety of ultrasound-assisted catheter-directed thrombolysis (USAT) compared to anticoagulation ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40281654/

Clinical Outcomes in Patients With Acute Pulmonary ... USAT effectively reduces right ventricular overload and mean pulmonary artery pressure with low rates of in-hospital mortality and bleeding.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2213333X18301410

A meta-analysis of outcomes of catheter-directed ... Catheter thrombolysis has high clinical success rates in both high- and intermediate-risk PE, but higher mortality and bleeding rates should be anticipated in ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666572725000094

Ultrasound assisted, catheter-directed thrombolysis for ... Data regarding CDT are promising in terms of safety and efficacy, showing acute improvement in right ventricular (RV) function and a reduction in pulmonary ...

7. jacc.org jacc.org/doi/10.1016/j.jcin.2023.07.042

Efficacy and Safety of Anticoagulation, Catheter-Directed ... This study sought to compare the efficacy and safety of anticoagulation (AC) alone, catheter-directed thrombolysis (CDT), and systemic thrombolysis (ST) in ...

8. frontiersin.org frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.967786/full

A study level meta-analysis of clinical trials Clinical efficacy and safety of ultrasound-assisted thrombolysis vs. standard catheter-directed thrombolysis in patients with acute pulmonary ...