Peripheral Systemic Thrombolysis Versus Catheter Directed Thrombolysis for Submassive PE

NCT03581877 | Active Not Recruiting Phase 4 DMC FDA Drug FDA Device

• 1 other identifier: 18-0805
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

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)

Conditions

Pulmonary Embolism; Pulmonary Hypertension; Thromboembolism; Right Ventricular Dysfunction

Keywords

Alteplase; submassive pulmonary embolism; Thrombolysis; pulmonary catheter

Outcome Measures

Primary Outcomes (2)

• Right ventricle (RV) to Left ventricle (LV) ratio

  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

  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 Outcomes (1)

• Mortality

  30 days

Other Outcomes (2)

• Right ventricle (RV) to Left ventricle (LV) ratio

  30 days

• Pulmonary pressures

  30 days

Study Arms (2)

Peripheral low dose thrombolysis

EXPERIMENTAL

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

Catheter directed acoustic thrombolysis

ACTIVE COMPARATOR

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

Interventions

Alteplase DRUG

As stated before, low dose r-tpa will be administered through a peripheral vein for PLST.

Also known as: Peripheral low dose systemic thrombolysis (PLST)

Peripheral low dose thrombolysis

EKOS DEVICE

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.

Also known as: Ultrasound assisted catheter directed thrombolysis (ACDT)

Catheter directed acoustic thrombolysis

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Age \<18 to age \>90 years;
• PE symptom duration \>14 days;
• Administration of thrombolytic drugs in the last 4 days
• Contraindications to thrombolytic therapy:
• Active bleeding disorder or coagulation disorder;
• Platelet count \<100 000/mm3
• Hematocrit \< 30%
• INR\> 3
• Previous history of vitamin K antagonists with international normalized ratio \>2.5 on admission
• History of intracranial or intraspinal surgery or trauma or intracranial/intraspinal bleeding
• Intracranial neoplasm
• Arteriovenous malformation, or aneurysm
• Gastrointestinal bleeding \<3 months
• Internal eye surgery or hemorrhagic retinopathy less than three-month duration
• Major surgery, cataract surgery, obstetric delivery, cardiopulmonary resuscitation, or invasive procedure less than10 days duration

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (2)

Southside Northwell Hospital

Bay Shore, New York, 11706, United States

Location

Long Island Jewish Medical Center

Queens, New York, 11040, United States

Location

Related Publications (10)

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  PMID: 21422387 BACKGROUND

• Kucher N, Boekstegers P, Muller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Muller R, Blessing E, Greif M, Lange P, Hoffmann RT, Werth S, Barmeyer A, Hartel D, Grunwald H, Empen K, Baumgartner I. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014 Jan 28;129(4):479-86. doi: 10.1161/CIRCULATIONAHA.113.005544. Epub 2013 Nov 13.

  PMID: 24226805 BACKGROUND

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  PMID: 19833379 BACKGROUND

MeSH Terms

Conditions

Pulmonary Embolism; Hypertension, Pulmonary; Thromboembolism; Ventricular Dysfunction, Right

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Hypertension; Ventricular Dysfunction; Heart Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Azhar Supariwala, MD

  Southside Northwell Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Structural Imaging Southside Hospital Northwell Health

Model Details: This study will be a prospective randomized interventional study. Patients referred to Southside hospital will be consented to take part in the study. After obtaining written informed consent, investigators will subsequently enroll 158 consecutive patients (aged\> 18 years) randomized in a serial 1:1 allocation for either low dose PLST or ACDT for submassive pulmonary embolism.

Study Record Dates

• First Submitted: May 7, 2018
• First Posted: July 10, 2018
• Study Start: January 28, 2019
• Primary Completion: March 19, 2023
• Study Completion: March 19, 2025
• Last Updated: October 3, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)