tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden

Study Overview
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Brief Summary
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To demonstrate the efficacy and safety of the Bashir™ Endovascular Catheter for the administration of pharmaco-mechanical catheter directed therapy using low dose r-tPA for the treatment of acute submassive pulmonary embolism.

Detailed Description
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The Bashir™ Endovascular Catheter has been designed to administer therapeutic agents in the peripheral vasculature. Because of the unique design of the catheter, with its six expandable infusion limbs, the Bashir™ Endovascular Catheter has the ability to: 1. Create a much larger central channel for blood flow, thereby utilizing the body's own endogenous fibrinolytic agents to lyse the clot, and 2. Greatly enhance the radial dispersion of a catheter-administered thrombolytic agent throughout the thrombus. Expansion of the multiple arms of the basket in the infusion catheter causes fissuring of the clot. The net result is that a greater surface area of clot is exposed to both endogenous and exogenously administered lytic agents, thereby promoting clot dissolution. This study will utilize the Bashir™ Endovascular Catheter and the Bashir Endovascular Catheter with a short basket (BASHIR™ S-B endovascular catheter) to administer catheter directed thrombolysis in patients with submassive PE who have consented and meet all eligibility criteria. The Bashir™ and BASHIR™ S-B endovascular catheters represent a new methodology for localized catheter-based delivery of thrombolytics. The thrombolytic to be used in this study is r-tPA (Genentech Corporation, South San Francisco, USA). The design of the Bashir Endovascular Catheter with the multiple infusion limbs creating a basket-like formation when expanded, provides an immediate channel for blood flow through the thrombus and a greater surface area in the thrombus for the endogenous and exogenous thrombolytics to take effect, as described above.

Official Title
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Recombinant tPA by Endovascular Administration for the Treatment of Submassive Pulmonary Embolism Using Pharmaco-mechanical Catheter Directed Thrombolysis for the redUction of Thrombus burdEn

Conditions
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Pulmonary Embolism

Intervention / Treatment
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* Device: The Bashir™ Endovascular Catheter
* Drug: r-tPA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide informed consent; Age 18 to ≤ 75 years of age; PE symptom duration ≤ 14 days. Filling defect in at least one main or lobar pulmonary artery as determined by contrast enhanced chest CT (CTA); RV/LV diameter ratio ≥ 0.9 by CTA as determined by the investigative site; Willing and able to comply with all study procedures and follow-up. Exclusion Criteria: CVA or TIA within one (1) year; Head trauma, active intracranial, or intraspinal disease ≤ one (1) year prior to inclusion in the study; Active bleeding from a major organ within one (1) month prior to inclusion in the study; Intracranial condition(s) that may increase the risk of bleeding (e.g., neoplasms, arteriovenous malformations, or aneurysms); Patients with bleeding diatheses; Hematocrit < 30%; Platelets < 100,000/μL; INR > 1.5 if currently on warfarin (Coumadin®); aPTT > 50 seconds in the absence of anticoagulants; Major surgery ≤ 14 days prior to inclusion in the study; Serum creatinine > 2.0mg/dL; Clinician deems high-risk for catastrophic bleeding; History of heparin-induced thrombocytopenia (HIT Syndrome); Pregnancy; SBP < 90 mmHg > 15 minutes within two (2) hours prior to BEC procedure and is not resolved with IV fluids; Any vasopressor support; Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR) during this hospitalization at treating institution and/or referring institution; Evidence of irreversible neurological compromise; Life expectancy < one (1) year; Use of thrombolytics or glycoprotein IIb/IIIa inhibitor within 3 days prior to inclusion in the study; Use of non-vitamin K oral anti-coagulants (NOACs), such as rivaroxaban (Xarelto®), apixaban (Eliquis®), dabigatran (Pradaxa®), edoxaban (Savaysa®) within 48 hours prior to inclusion in the study; Profound bradycardia requiring a temporary pacemaker and/or inotropic support; Previous enrollment in this study; Morbidly obese patient who by the judgement of the investigator is high risk for bleeding; BMI > 45kg/m2; Absolute contraindication to anticoagulation; Uncontrolled hypertension defined as SBP > 175mmHg and / or DBP > 110mmHg with pharmacotherapy within two (2) hours prior to inclusion in the study; Currently participating in another study; Any arterial line placement; Current positive COVID diagnosis, or ≤ 8 weeks negative of COVID, or > 8 weeks from positive COVID test and with current symptoms, or current active viral pneumonia on chest CT scan; In the opinion of the investigator, the subject is not a suitable candidate for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Pulse Spray and Infusion of r-tPA
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEC Treatment<br>The Bashir™ Endovascular Catheter is a device intended for the localized infusion of therapeutic agents into the pulmonary artery. | Device: The Bashir™ Endovascular Catheter<br>* The Bashir™ Endovascular Catheter is a device intended for the localized infusion of therapeutic agents into the pulmonary artery and peripheral vasculature.<br>Drug: r-tPA<br>* Pulse spray and infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: RV/LV Ratio Difference | Observe RV/LV diameter ratio difference between baseline and 48 hours after the completion of r-tPA treatment as measured by contrast enhanced chest CT (CTA). | 48 hours after the completion of r-tPA treatment | 
| Safety: Major Bleeding | Major Bleeding as defined by International Society of Thrombosis and Hemostasis (ISTH), within 72 hours of initiation of r-tPA administration. Bleeding criteria are as follows: Major Bleeding in Non-Surgical Patients Fatal bleeding; and/or Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome; and/or Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more or leading to transfusion of two or more units of whole blood or red cells. | Within 72 hours of initiation of r-tPA administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Embolism, Catheter Directed Therapy