Catheter-Directed Therapy for Pulmonary Embolism

(PE-TRACT Trial)

Recruiting at 46 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

Trial Summary

What is the purpose of this trial?

PE-TRACT is an open-label, assessor-blinded, randomized trial, aiming to compare catheter-directed therapy (CDT) and anticoagulation (CDT group) with anticoagulation alone (No-CDT) in 500 patients with submassive PE, proximal pulmonary artery thrombus and right ventricular dilation.

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.

What data supports the idea that Catheter-Directed Therapy for Pulmonary Embolism is an effective treatment?

The available research shows that traditional anticoagulant therapy, which includes drugs like heparin and vitamin K antagonists, has been effective in reducing mortality from pulmonary embolism from 25% to 6%. However, the research does not provide specific data on the effectiveness of Catheter-Directed Therapy for Pulmonary Embolism compared to these traditional treatments. Instead, it highlights the effectiveness of anticoagulant drugs in general, with a low recurrence rate of about 5% and very rare lethal recurrences. While Catheter-Directed Therapy might be used in certain cases, the data provided focuses on the success of anticoagulant drugs in treating pulmonary embolism. ^{1 2 3 4 5}

What safety data exists for catheter-directed therapy for pulmonary embolism?

Catheter-directed therapy (CDT) is considered a promising option for treating pulmonary embolism, particularly for minimizing bleeding risk compared to other interventions. While systemic thrombolysis is the mainstay for hemodynamically unstable patients, CDT offers a targeted approach that may reduce bleeding complications. The safety of CDT, including ultrasound-assisted catheter-directed thrombolysis (USAT), is still being evaluated, but it is seen as a potentially safer alternative to systemic thrombolysis, especially for intermediate-risk patients. The data on reduced-dose intravenous thrombolysis is still preliminary, and the use of non-vitamin K-dependent oral anticoagulants has been shown to reduce major bleeding risk in long-term anticoagulation. ^{6 7 8 9 10}

Is the drug Anticoagulant Therapy a promising treatment for Pulmonary Embolism?

Anticoagulant Therapy is a standard treatment for Pulmonary Embolism and is effective for many patients. However, for some patients who do not respond well to it, Catheter-Directed Therapy has shown promising results. ^{1 11 12 13 14}

Research Team

Sunil Rao, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. France pubmed.ncbi.nlm.nih.gov

[Anticoagulant therapy in pulmonary embolism]. [2017]

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

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

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

Pulmonary embolism in the critically ill. [2007]

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

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

6. England 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. [2023]

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

Treatment of venous thromboembolic disease. A pragmatic approach to anticoagulation and thrombolysis. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Prevalence of Hemorrhagic Complications in Hospitalized Patients with Pulmonary Embolism. [2022]

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

Comparison of interventions for intermediate to high-risk pulmonary embolism: A network meta-analysis. [2023]

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

Risk-adapted management of pulmonary embolism. [2022]

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

Catheter-directed therapy for submassive pulmonary embolism after unsuccessful systemic thrombolysis. [2020]

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

Contemporary Management of Acute Pulmonary Embolism: Evolution of Catheter-based Therapy. [2022]

13. Poland pubmed.ncbi.nlm.nih.gov

Initial results of investigator initiated international database on catheter directed therapy of acute pulmonary embolism. [2023]

14. Spain pubmed.ncbi.nlm.nih.gov

Catheter-directed therapy for acute pulmonary embolism: results of a multicenter national registry. [2023]