Pulmonary Embolism
Conditions
Keywords
Pulmonary Embolism, Catheter Directed Therapy
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.
Interventions
The Bashir™ Endovascular Catheter is a device intended for the localized infusion of therapeutic agents into the pulmonary artery and peripheral vasculature.
DRUGr-tPA
Pulse spray and infusion
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Thrombolex, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Pulse Spray and Infusion of r-tPA
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BEC Treatment The Bashir™ Endovascular Catheter is a device intended for the localized infusion of therapeutic agents into the pulmonary artery.
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.
r-tPA: Pulse spray and infusion | 109 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | BEC Treatment |
|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 13.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 64 Participants |
| Region of Enrollment United States | 109 participants |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 109 |
| other Total, other adverse events | 18 / 109 |
| serious Total, serious adverse events | 7 / 109 |
Outcome results
Primary
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).
Time frame: 48 hours after the completion of r-tPA treatment
Population: Subjects treated with the Bashir™ Endovascular Catheter and had analyzable baseline and 48 hour CTAs.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| BEC Treatment | Efficacy: RV/LV Ratio Difference | RV/LV Ratio at Baseline (R0) | 1.66 RV/LV Ratio |
| BEC Treatment | Efficacy: RV/LV Ratio Difference | RV/LV Ratio within 48 hours of completion of treatment (R48) | 1.10 RV/LV Ratio |
| BEC Treatment | Efficacy: RV/LV Ratio Difference | Difference (R48-R0) | -0.56 RV/LV Ratio |
Primary
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 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.
Time frame: Within 72 hours of initiation of r-tPA administration
Population: Subjects treated with the Bashir™ Endovascular Catheter
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BEC Treatment | Safety: Major Bleeding | 1 Participants |