Peripheral Systemic Thrombolysis Versus Catheter Directed Thrombolysis for Submassive PE

March 19, 2023 updated by: Azhar Supariwala MD, FACC, FASE, Northwell Health

Peripheral Low Dose Systemic Thrombolysis Versus Catheter Directed Acoustic Pulse Thrombolysis for Treatment of Submassive Pulmonary Embolism

To determine whether peripheral low dose systemic thrombolysis (PLST) is non-inferior to catheter directed acoustic pulse thrombolysis (ACDT) in improving RV function and reducing pulmonary artery pressures in submassive pulmonary embolism (PE)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Acute pulmonary embolism (PE) is a life-threatening event associated with high morbidity and mortality. With more than 100,000 deaths per year, PE constitutes the third most common cardiovascular cause of death following myocardial infarction and stroke. In non massive PE, anticoagulation is the treatment of choice. Advanced treatment options such as systemic thrombolysis in submassive and massive PE help reduce mortality but unfortunately are associated with bleeding complications such as a 2 to 5% risk of hemorrhagic stroke.This has led to development of pharmaco-mechanical therapies such as catheter directed thrombolysis (CDT).

Current guidelines advocate against the use of full dose systemic thrombolysis for acute submassive PE in all patients unless the bleeding risk is very low. CDT has shown efficiency in reducing right ventricular strain and pulmonary hypertension without increasing bleeding complications in trial populations. Ultrasound assisted CDT (ACDT) is an established treatment modality for acute PE which utilizes high frequency low power ultrasonic waves. It is FDA approved for sub-massive and massive pulmonary embolism. However, ultrasound does not breakdown the thrombus itself but increases the permeability for thrombolytic drugs. The ULTIMA trial showed ACDT was superior to anticoagulation treatment in reducing pulmonary hypertension (PH) and right ventricular dilatation in submassive and massive PE. The trial also reported no intracranial hemorrhage. The exact benefit and mechanism of ACDT in dissolving clots is still not clear. Recently, the PERFECT registry described 100 patients who underwent CDT (64%) and ACDT (46%) for PE, the study showed no difference in reduction of pulmonary artery pressures.

ACDT requires the placement of catheters in the pulmonary arteries in a catheterization laboratory by an interventional cardiologist/radiologist through the internal jugular vein/femoral vein and catheters are kept for 12-24 hrs to infuse recombinant tissue plasminogen activator (r-tpa). While many healthcare systems have developed a pulmonary embolism response team (PERT) to make a prompt therapeutic decision in submassive and massive pulmonary embolism management. However, it is not uncommon for CDT to be delayed (sometimes > 12 hours) after the initial diagnosis due to the availability of the interventional cardiologist. Furthermore, placement of pulmonary catheters in CDT can have the risk, albeit low, of pulmonary vasculature injury.

The investigators hypothesize that low dose thrombolytic therapy can be administered through a peripheral vein. PLST is rapidly administrable and does not require placement in a catheterization laboratory by an interventional cardiologist. In addition, the use of low dose r-tpa reduces risk of major bleeding complications. The investigators aim to see if equivalent low dose r-tpa given peripherally i.e PLST is non-inferior to ACDT for the treatment of submassive PE. Both treatments will be compared in safety, efficacy and overall cardiopulmonary function.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Bay Shore, New York, United States, 11706
        • Southside Northwell Hospital
      • Queens, New York, United States, 11040
        • Long Island Jewish Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18 years or older, able to consent
  2. Submassive PE evidenced by CT showing saddle pulmonary embolism, central right and/or left main pulmonary artery emboli.
  3. Submassive PE confirmed by right ventricular dimension to left ventricular dimension ratio ≥ 1 in apical 4-chamber view echo/CT scan.
  4. Signs of RV dysfunction by echocardiogram, or elevated troponin I >0.04, or pro-BNP > 400 on serial measurements.
  5. PE symptom duration less than or equal to 14 days -

Exclusion Criteria:

  1. Age <18 to age >90 years;
  2. PE symptom duration >14 days;
  3. Administration of thrombolytic drugs in the last 4 days

  4. Contraindications to thrombolytic therapy:

    1. Active bleeding disorder or coagulation disorder;
    2. Platelet count <100 000/mm3
    3. Hematocrit < 30%
    4. INR> 3
    5. Previous history of vitamin K antagonists with international normalized ratio >2.5 on admission
    6. History of intracranial or intraspinal surgery or trauma or intracranial/intraspinal bleeding
    7. Intracranial neoplasm
    8. Arteriovenous malformation, or aneurysm
    9. Gastrointestinal bleeding <3 months
    10. Internal eye surgery or hemorrhagic retinopathy less than three-month duration
    11. Major surgery, cataract surgery, obstetric delivery, cardiopulmonary resuscitation, or invasive procedure less than10 days duration
    12. Allergy, hypersensitivity, or thrombocytopenia caused heparin or tPA
  5. Severe contrast allergy to iodinated contrast
  6. Large (>10 mm) right atrial or right ventricular thrombus
  7. Systolic blood pressure <90 mm Hg
  8. Severe hypertension on repeat measurement (systolic >180 mm Hg or diastolic >105 mm Hg)
  9. Pregnancy
  10. In any other investigational drug or device study

  11. Inability to follow instructions or comply with treatment

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Peripheral low dose thrombolysis
Peripheral low dose thrombolysis will use a peripheral vein into an arm as in routine intravenous therapy. This is the experimental arm. Alteplate (R-tpa) belong to thrombolytic or fibrnolytic drug class. Routine hospital policies for peripheral venous therapy will be used. A fixed dose of 24 mg of Activase (Atleplase) over 12 hours or 2.0 mg/hr will be administered peripherally. Simultaneously, intravenous unfractionated heparin will be given with a target partial thromboplastin time of 40 to 60 secs.
Drug: Alteplase
As stated before, low dose r-tpa will be administered through a peripheral vein for PLST.
Other Names:
  • Peripheral low dose systemic thrombolysis (PLST)
Active Comparator: Catheter directed acoustic thrombolysis
For ACDT, routine hospital protocols and EKOS(generic) will be used. EKOS is made up of 3 parts which include the drug delivery pulmonary artery catheter, a removable microsonic device, and a reusable Eko-Sonic control unit. Venous access will be obtained by ultrasound guidance in the internal jugular vein or femoral vein. After catheter placement, the right heart pressures will be measured. R-tpa will be directly given into the pulmonary catheter. A fixed dose of 24 mg of tpa over 12 hours or 2.0mg/hr will be given. For unilateral PE, a single catheter will be used with infusion rate of 2 mg//hr and two catheters will be used for bilateral PEs each with 1 mg /hr infusion rate. Intravenous unfractionated heparin will be given with a target partial thromboplastin time of 40 to 60 secs.
Device: EKOS
As stated before, the EKos device will be used for ultrasound assisted catheter directed thrombolysis or ACDT, same dose t-tpa will administered through the pulmonary catheter. It will be given at a fixed dose over 24 hours.
Other Names:
  • Ultrasound assisted catheter directed thrombolysis (ACDT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Right ventricle (RV) to Left ventricle (LV) ratio
Time Frame: 48 hours
Investigators will measure and compare the change between baseline and 48 hours right ventricular diameter to left ventricular diameter (RV:LV ratio) on echocardiogram after PLST or ACDT
48 hours
Pulmonary pressures
Time Frame: 48 hours
Investigators will measure and compare the change between baseline and 48 hours pulmonary pressures (mm Hg) with echocardiogram following therapy with PLST or ACDT therapy.
48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 30 days
Composite of all-cause mortality and fatal bleeding in-hospital and at 30-day
30 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Right ventricle (RV) to Left ventricle (LV) ratio
Time Frame: 30 days
Investigators will measure and compare the change between baseline and 30 days right ventricular diameter to left ventricular diameter (RV:LV ratio) on echocardiogram after PLST or ACDT
30 days
Pulmonary pressures
Time Frame: 30 days
Investigators will measure and compare the change between baseline and 30 days pulmonary pressures (mm Hg) with echocardiogram following therapy with PLST or ACDT therapy.
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwell Health

Investigators

  • Principal Investigator: Azhar Supariwala, MD, Southside Northwell Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 28, 2019

Primary Completion (Actual)

March 19, 2023

Study Completion (Actual)

March 19, 2023

Study Registration Dates

First Submitted

May 7, 2018

First Submitted That Met QC Criteria

June 26, 2018

First Posted (Actual)

July 10, 2018

Study Record Updates

Last Update Posted (Actual)

March 21, 2023

Last Update Submitted That Met QC Criteria

March 19, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-0805

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Investigators are not planning to share information or participant data with other researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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