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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Embolism
• Intervention / Treatment: Drug: r-tPA; Device: The Bashir™ Endovascular Catheter

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 Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cardiac & Vascular Institute
    • Orlando, Florida, United States, 32803
      • Advent Health Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
    • Atlanta, Georgia, United States, 30308
      • Emory
  • Illinois
    • Maywood, Illinois, United States, 60521
      • Loyola University Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Ascension St. Vincent
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Ascension St. John Hospital
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Hospital, Royal Oak
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • Liverpool, New York, United States, 13088
      • St. Joseph's Hospital
    • New York, New York, United States, 10016
      • NYU Langone
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • NC Heart
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Mt Carmel
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16550
      • UPMC Hamot
    • Philadelphia, Pennsylvania, United States, 19122
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Heart and Vascular Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37934
      • Tennova Heart - Turkey Creek
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • CAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Thrombolex, Inc.
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Brian Firth, MD, PhD, MBA, FACC, Thrombolex, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2020
• Primary Completion (Actual): June 22, 2022
• Study Completion (Actual): June 23, 2022

Study Registration Dates

• First Submitted: January 28, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (Actual): January 30, 2020

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Pulmonary Embolism; Catheter Directed Therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism
• Other Study ID Numbers: THRO-CLIN-2019-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes