Clinical trial NCT06120179: The RESCUE II Study. The Bashir™ Endovascular Catheter (BEC),
Official title: Recombinant tPA by Endovascular Pulse 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: NOT_YET_RECRUITING
Phase: NA
Conditions: Acute Submassive Pulmonary Embolism
Lead sponsor: Temple University
Sponsor class: OTHER
First posted: 2023-11-07
Enrollment: 20
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: Prospective, non-randomized, multi-center study. The Bashir™ Endovascular Catheter (BEC
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 pulse spray of r-tPA for the treatment of acute submassive pulmonary embolism

Detailed description: Study Objective To demonstrate the efficacy and safety of the Bashir™ and Bashir™ S-B Endovascular Catheters for the administration of pharmaco- mechanical catheter directed therapy in a pulse spray mode using low dose r-tPA for the treatment of acute submassive pulmonary embolism. Endpoints Primary Efficacy Endpoint Reduction in RV/LV diameter ratio as measured by CTA within 48 hours after the completion of r-tPA treatment.

Primary Safety Endpoint Major bleeding, as defined by International Society of Thrombosis and Hemostasis (ISTH), within 72 hours of initiation of r- tPA infusion. ISTH major bleeding in non-surgical patients is defined as having a symptomatic presentation and:

a. Fatal bleeding; and/or b. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra- articular or pericardial, or intramuscular with compartment syndrome; and/or c. Bleeding causing a fall in hemoglobin level of 2.0g/dL (1.24mmol/L) or more or leading to transfusion of two or more units of whole blood or red cells. Secondary Endpoints

1. Refined Modified Miller Score as measured on CTA within 48 hours after the completion of the r-tPA infusion compared to baseline as measured by core lab. 25
2. All-cause mortality at hospital discharge through 30-day follow-up.
3. SAEs through 30-day follow-up.
4. AEs through 30-day follow-up.
5. UADEs through 30-day follow-up.
6. Recurrent PE through 30-day follow-up.
7. Clinically Relevant Non-Major bleeding: Any sign or symptom of hemorrhage (e.g. more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria:

   1. Requiring medical intervention by a healthcare professional.
   2. Leading to hospitalization or increased level of care.
   3. Prompting a face to face (i.e., not just a telephone or electronic communication) evaluation.
8. Technical procedural complications.
9. Systolic PA pressure measured at completion of pulse sprays and after BEC(s) removal and compared to baseline.
10. Cardiac output (CO by Modified Fick calculation) and cardiac index (CI) following completion of the r-tPA pulse sprays compared to the baseline. Please refer to Terms and Definitions section for the Modified Fick calculation to be done in the IR suite / cath lab at baseline and after BEC removal).

Eligibility criteria: Inclusion 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 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. Profound bradycardia requiring a temporary pacemaker and/or inotropic support;
22. Absolute contraindication to anticoagulation;
23. Uncontrolled hypertension defined as SBP \> 175mmHg and / or DBP \> 110mmHg with pharmacotherapy within two (2) hours prior to inclusion in the study;
24. Currently participating in another study;
25. In the opinion of the investigator, the subject is not a suitable candidate for the study

Primary outcomes:
measure: Reduction in RV/LV diameter ratio as measured by contrast enhanced chest CT from baseline within 48 ± 6 hours of initiation of treatment. chest CT (CTA) within 48 hours after the completion of r-tPA treatment
timeFrame: Through 30 day follow-up
measure: Primary Safety Endpoint, major bleeding, as defined by International Society of Thrombosis and Hemostasis (ISTH), within 72 hours of initiation of rtPA infusion. ISTH major bleeding in non-surgical patients is defined as having a symptomatic presentation
timeFrame: 72 hours
Secondary outcomes:
measure: Refined Modified Miller Score
timeFrame: Within 48 hours of completion of r-TPA
measure: All-cause mortality
timeFrame: 30 DAYS
measure: Serious adverse events
timeFrame: 30 days
measure: Adverse events
timeFrame: 30 days
measure: Unanticipated adverse device events
timeFrame: 30 days
measure: Recurrent pulmonary embolism through 30-day follow-up.
timeFrame: 30 days
measure: Clinically relevant non-major bleeding
timeFrame: 30 days
measure: Technical procedural complications.
timeFrame: 1 day
measure: Systolic PA pressure
timeFrame: Once r-tPA pulse sprays are given continue therapeutic anticoagulation with full does heparin or LMWH with sheaths sutured in place
measure: Cardiac output (CO by Modified Fick calculation) and cardiac index (CI) following completion of the r-tPA pulse
timeFrame: End of procedure
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
Study officials:
affiliation: Temple University
name: Parth Rali, MD
role: PRINCIPAL_INVESTIGATOR
References: