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

Phase 3

Completed

• Conditions: Pulmonary Embolism
• Interventions: Device: The Bashir™ Endovascular Catheter; Drug: r-tPA

• Registration Number: NCT04248868
• Lead Sponsor: Thrombolex, Inc.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-01-28
• Study First Submitted QC: 2020-01-28
• Study First Posted: 2020-01-30
• Study Start: 2020-06-23
• Primary Completion: 2022-06-22
• Study Completion: 2022-06-23
• Status Verified: 2023-03
• Results First Submitted: 2023-03-29
• Results First Submitted QC: 2023-03-29
• Last Update Submitted: 2023-03-29
• Results First Posted: 2023-04-20
• Last Update Posted: 2023-04-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 109

Inclusion Criteria

1. Willing and able to provide informed consent;
2. Age 18 to ≤ 75 years of age;
3. PE symptom duration ≤ 14 days.
4. Filling defect in at least one main or lobar pulmonary artery as determined by contrast enhanced chest CT (CTA);
5. RV/LV diameter ratio ≥ 0.9 by CTA as determined by the investigative site;
6. Willing and able to comply with all study procedures and follow-up.

Exclusion Criteria

1. CVA or TIA within one (1) year;
2. Head trauma, active intracranial, or intraspinal disease ≤ one (1) year prior to inclusion in the study;
3. Active bleeding from a major organ within one (1) month prior to inclusion in the study;
4. Intracranial condition(s) that may increase the risk of bleeding (e.g., neoplasms, arteriovenous malformations, or aneurysms);
5. Patients with bleeding diatheses;
6. Hematocrit < 30%;
7. Platelets < 100,000/μL;
8. INR > 1.5 if currently on warfarin (Coumadin®);
9. aPTT > 50 seconds in the absence of anticoagulants;
10. Major surgery ≤ 14 days prior to inclusion in the study;
11. Serum creatinine > 2.0mg/dL;
12. Clinician deems high-risk for catastrophic bleeding;
13. History of heparin-induced thrombocytopenia (HIT Syndrome);
14. Pregnancy;
15. SBP < 90 mmHg > 15 minutes within two (2) hours prior to BEC procedure and is not resolved with IV fluids;
16. Any vasopressor support;
17. Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR) during this hospitalization at treating institution and/or referring institution;
18. Evidence of irreversible neurological compromise;
19. Life expectancy < one (1) year;
20. Use of thrombolytics or glycoprotein IIb/IIIa inhibitor within 3 days prior to inclusion in the study;
21. 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;
22. Profound bradycardia requiring a temporary pacemaker and/or inotropic support;
23. Previous enrollment in this study;
24. Morbidly obese patient who by the judgement of the investigator is high risk for bleeding;
25. BMI > 45kg/m2;
26. Absolute contraindication to anticoagulation;
27. Uncontrolled hypertension defined as SBP > 175mmHg and / or DBP > 110mmHg with pharmacotherapy within two (2) hours prior to inclusion in the study;
28. Currently participating in another study;
29. Any arterial line placement;
30. 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;
31. In the opinion of the investigator, the subject is not a suitable candidate for the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BEC Treatment	The Bashir™ Endovascular Catheter	The Bashir™ Endovascular Catheter is a device intended for the localized infusion of therapeutic agents into the pulmonary artery.
BEC Treatment	r-tPA	The Bashir™ Endovascular Catheter is a device intended for the localized infusion of therapeutic agents into the pulmonary artery.

Primary Outcome Measures

Name	Time	Method
Efficacy: RV/LV Ratio Difference	48 hours after the completion of r-tPA treatment	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).
Safety: Major Bleeding	Within 72 hours of initiation of r-tPA administration	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; 1. Fatal bleeding; and/or; 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome; and/or; 3. 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.

Trial Locations

Locations (19)

Mt Carmel; 🇺🇸 Columbus, Ohio, United States

UCLA; 🇺🇸 Los Angeles, California, United States

Emory; 🇺🇸 Atlanta, Georgia, United States

Ascension St. Vincent; 🇺🇸 Indianapolis, Indiana, United States

Advent Health Orlando; 🇺🇸 Orlando, Florida, United States

NYU Langone; 🇺🇸 New York, New York, United States

Piedmont Heart Institute; 🇺🇸 Atlanta, Georgia, United States

Loyola University Chicago; 🇺🇸 Maywood, Illinois, United States

Ascension St. John Hospital; 🇺🇸 Detroit, Michigan, United States

St. Joseph's Hospital; 🇺🇸 Liverpool, New York, United States

UPMC Hamot; 🇺🇸 Erie, Pennsylvania, United States

Beaumont Hospital, Royal Oak; 🇺🇸 Royal Oak, Michigan, United States

NC Heart; 🇺🇸 Raleigh, North Carolina, United States

Temple University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

UPMC Heart and Vascular Institute; 🇺🇸 Pittsburgh, Pennsylvania, United States

Miami Cardiac & Vascular Institute; 🇺🇸 Miami, Florida, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Tennova Heart - Turkey Creek; 🇺🇸 Knoxville, Tennessee, United States

CAMC; 🇺🇸 Charleston, West Virginia, United States