Clinical trial NCT04248868: tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden
Official title: Recombinant tPA by Endovascular Administration for the Treatment of Submassive Pulmonary Embolism Using Pharmaco-mechanical Catheter Directed Thrombolysis for the redUction of Thrombus burdEn
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Embolism
Keywords: Pulmonary Embolism
Catheter Directed Therapy
Lead sponsor: Thrombolex, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2020-01-30
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Pulse Spray and Infusion of r-tPA
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy: RV/LV Ratio Difference
timeFrame: 48 hours after the completion of r-tPA treatment
measure: Safety: Major Bleeding
timeFrame: Within 72 hours of initiation of r-tPA administration
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Miami
country: United States
facility: Miami Cardiac & Vascular Institute
state: Florida
city: Orlando
country: United States
facility: Advent Health Orlando
state: Florida
city: Atlanta
country: United States
facility: Emory
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Maywood
country: United States
facility: Loyola University Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent
state: Indiana
city: Detroit
country: United States
facility: Ascension St. John Hospital
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital, Royal Oak
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Liverpool
country: United States
facility: St. Joseph's Hospital
state: New York
city: New York
country: United States
facility: NYU Langone
state: New York
city: Raleigh
country: United States
facility: NC Heart
state: North Carolina
city: Columbus
country: United States
facility: Mt Carmel
state: Ohio
city: Erie
country: United States
facility: UPMC Hamot
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Heart and Vascular Institute
state: Pennsylvania
city: Knoxville
country: United States
facility: Tennova Heart - Turkey Creek
state: Tennessee
city: Charleston
country: United States
facility: CAMC
state: West Virginia
Study officials:
affiliation: Thrombolex, Inc.
name: Brian Firth, MD, PhD, MBA, FACC
role: PRINCIPAL_INVESTIGATOR
References: