Conditions: Pulmonary Embolism
Keywords: Pulmonary Embolism Catheter Directed Therapy
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 109
Healthy volunteers: no

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.

Arms:
arm 1: The Bashir™ Endovascular Catheter is a device intended for the localized infusion of therapeutic agents into the pulmonary artery.

Interventions: intervention 1: The Bashir™ Endovascular Catheter intervention 2: r-tPA
Intervention descriptions: intervention 1: The Bashir™ Endovascular Catheter is a device intended for the localized infusion of therapeutic agents into the pulmonary artery and peripheral vasculature. intervention 2: Pulse spray and infusion

Protocol document:
Prot_SAP_000.pdf: 
Thrombolex, Inc. Pivotal IDE Study                          Confidential                                           IDE: G200009 
Protocol THRO-CLIN-2019-01 Version  4.0         August 18, 2020          Page 1 of 74 
This protocol is confidential property of Thrombolex, Inc and in no way should be distributed all or in 
part without written permission from Thrombolex, Inc. 
Clinical Protocol 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 - The RESCUE Study 
Protocol Number 
THRO-CLIN-2019-01 
Study Phase 
Phase III – Pivotal Study  
Device Phase 
Pre-market 
Study Sponsor 
Thrombolex, Inc. 
75 Britain Drive  
New Britain, PA 18901 
Current Protocol Version 
4.0 
Version Date 
August 18, 2020 
Previous Version 
N/A 
Steering Committee 
Anthony J. Comerota MD, FACS, FACC 
Kenneth Rosenfield MD, MSCAI, FACC 
Akhilesh K. Sista MD, FSIR, FAHA 
Victor Tapson MD, FCCP, FRCP 
Data Safety Monitoring 
Board Chairperson 
Gregory Piazza, MD, MS 
 
 
SAE Reporting 
Diane Horwitz, PhD 
Eminence Clinical Research, Inc. 
 
 
Sponsor Approval 
Approval Date 
Brian G. Firth, MD, PhD, MBA, FACC 
August 18, 2020 
Chief Scientific Officer 
 
Thrombolex, Inc. 
 
 
 
 
 
 
 
 
 
 
 
NCT04248868


Thrombolex, Inc. Pivotal IDE Study                          Confidential                                           IDE: G200009 
Protocol THRO-CLIN-2019-01 Version  4.0         August 18, 2020          Page 2 of 74 
This protocol is confidential property of Thrombolex, Inc and in no way should be distributed all or in 
part without written permission from Thrombolex, Inc. 
 
TABLE OF CONTENTS 
1.0 
PROTOCOL SYNOPSIS 
5 
2.0 
STUDY CONTACTS 
10 
3.0 
TERMS AND DEFINITIONS 
11 
4.0 
BACKGROUND AND RATIONALE 
15 
4.1 
Clinical Problem 
15 
4.2 
Current Treatment Options 
15 
4.3 
Study Rationale 
16 
4.4 
First-in-Man Study Results 
18 
5.0 
INVESTIGATIONAL DEVICE 
18 
Table 1. Bashir™ Endovascular Catheter Dimensions 
19 
6.0 
STUDY DESIGN 
20 
6.1 
Study Objective 
20 
6.2 
Endpoints  
20 
6.2.1 Primary Endpoint 
20 
6.2.2 Primary Safety Endpoint 
20 
6.2.3 Secondary Endpoints 
20 
6.3 
Eligibility Criteria 
21 
6.3.1 General Inclusion Criteria 
21 
6.3.2 General Exclusion Criteria 
21 
6.4 
Study Duration 
22 
6.4.1 Enrollment 
22 
6.4.2 COVID-19 Impact Assessment Form - Enrollment 
23 
6.4.3 Follow-up  
23 
6.4.4 COVID-19 Impact Assessment Form - Follow-Up Visits 
23 
6.4.5 Complete Study Period 
24 
6.4.6 Subject Participation 
24 
7.0 
METHODOLOGY 
24 
7.1 
Pre-Procedure Testing Within 48 Hours Pre-Procedure 
24 
7.1.1 Laboratory Tests 
24 
7.1.2 Imaging 
 
24 
7.1.3 Assessments 
25 
7.1.4 Anticoagulation 
25 
7.1.5 Data Collection 
26 
8.0 
IR SUITE / CATH LAB STUDY PROCEDURES 
27 
8.1 
Required Accessories and Supplies 
27 
8.1.1 Accessories to be provided by the IR suite / cath lab 
27 
8.1.2 Procedure Supplies Provided by the Sponsor 
28 
8.2 
Baseline Hemodynamic Readings 
28 
8.3 
r-tPA Administration - Prepare Pulse spray(s) and Infusion(s) prior to opening the BEC 
28 
8.3.1 Reconstitution of r-tPA Pulse Spray Mixture 
28 
Table 2. r-tPA Doses and Mixtures for Pulse Sprays and Infusions through the BEC 
29 
8.3.2 Reconstitution of r-tPA IV Infusion Mixture 
29 
9.0 
BASHIR™ ENDOVASCULAR CATHETER INVESTIGATIONAL PROCEDURE 
30 
9.1 
Baseline Readings - Summary of Procedure Steps 
30 
9.2 
Choose one of the two anticoagulation options below according to standard of care: 
30 
9.3 
Summary of Procedure Steps 
30 
9.3.1 Intra-procedure Data Collection Requirements 
31 
9.4 
Bashir Endovascular Catheter Use – Procedure Steps 
31 


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Protocol THRO-CLIN-2019-01 Version  4.0         August 18, 2020          Page 3 of 74 
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part without written permission from Thrombolex, Inc. 
9.5 
Pulse Spray of r-tPA for Unilateral and Bilateral PE 
32 
9.6 
r-tPA Infusion – Prior to Departing the IR Suite / Cath Lab 
32 
9.7 
Anticoagulation Post-BEC Procedure 
33 
9.8 
Maintaining Patency Through the Central Lumen of the BEC(s) During Transport to ICU 
33 
9.9 
Preparation in IR Suite / Cath Lab for Transfer to ICU 
33 
10.0 
POST-PROCEDURE PATIENT MANAGEMENT AND TESTS 
34 
10.1 
r-tPA Infusion – Intensive Care Unit 
34 
10.2 
Post-r-tPA Infusion: 
34 
10.3 
The Completion of r-tPA Infusion in the ICU 
34 
10.4 
Sheath Removal 
35 
11.0 
TESTS REQUIRED 24 HOURS AFTER COMPLETION OF THE R-TPA INFUSION 
35 
11.1 
Laboratory Tests and Other Tests 
35 
11.2 
Assessments 
35 
11.3 
Data Collection 
35 
12.0 
TESTS REQUIRED 48 HOURS AFTER COMPLETION OF THE R-TPA INFUSION 
36 
12.1 
Imaging 
 
36 
12.2 
Assessments 
36 
12.3 
Data Collection 
36 
13.0 
ASSESSMENTS REQUIRED 72 HOURS FOLLOWING START OF R-TPA INFUSION 
36 
13.1 
Assessments 
36 
13.2 
Data Collection 
36 
14.0 
ASSESSMENTS REQUIRED JUST PRIOR TO HOSPITAL DISCHARGE 
37 
14.1 
Assessments 
37 
15.0 
30-DAY FOLLOW-UP VISIT POST PROCEDURE 
37 
15.1 
Assessments 
37 
15.2 
Data Collection 
37 
16.0 
ANTICIPATED ADVERSE EVENTS 
37 
Table 3. Anticipated Adverse Events Related to the Investigational Device22 
38 
Table 4.  Anticipated Adverse Events Related to r-tPA Infusion15,19 
38 
Table 5. Anticipated Adverse Events Related to the Procedure23 
38 
17.0 
ADVERSE EVENT REPORTING 
39 
17.1 
Serious Adverse Events 
39 
17.2 
Unanticipated Adverse Device Effect 
40 
17.3 
Adverse Event Documentation 
40 
17.4 
Adverse Event Relatedness 
40 
Table 6. Adverse Event Categories of Study Device or Drug Relatedness 
41 
Table 7. Adverse Event Categories of Procedure Relatedness 
42 
17.5 
Investigator SAE Reporting Requirements 
42 
18.0 
REGULATORY REQUIREMENTS 
42 
18.1 
Investigator Responsibilities 
43 
18.2 
Sponsor Responsibilities 
45 
18.3 
Record Retention 
46 
18.4 
Emergency Circumstances 
46 
19.0 
DEVICE AND DRUG ACCOUNTABILITY 
46 
19.1 
Bashir™ Endovascular Catheter Packaging for the IR Suite / Cath Lab 
46 
19.2 
Device Accountability 
47 
19.3 
Drug Accountability 
47 
20.0 
STATISTICAL CONSIDERATIONS  
47 
20.1 
Power and Sample Size Calculation 
47 
20.2 
Endpoints, Hypotheses, and Analytical Methods 
48 
20.2.1 Primary Efficacy Endpoint: 
48 


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part without written permission from Thrombolex, Inc. 
20.2.2 Hypothesis: 
48 
20.2.3 Primary Safety Endpoint: 
49 
20.2.4 Hypothesis: 
49 
20.2.5 Secondary Endpoints: 
49 
20.2.6 Poolability, Subgroup, and Sensitivity Analysis 
50 
20.3 
Analysis Populations 
51 
21.0 
DATA SAFETY MONITORING BOARD 
52 
22.0 
STUDY STOPPING RULES 
52 
22.1 
General Study Stopping Rules 
52 
22.2 
Study Stopping Rules Related to Safety 
53 
22.2.1 Intracranial Hemorrhage 
53 
22.2.2 Bleeding  
53 
22.2.3 Ad Hoc Criteria for CEC/DSMB Meetings 
 
 
 
 
 
    52 
22.3 
Device Study Stopping Rules 
53 
22.3.1 Device Related SAEs 
53 
22.3.2 Device Malfunctions and Non-conformances 
53 
22.4 
Study Safety Reporting Requirements 
54 
23.0 
VERSION CONTROL 
55 
24.0 
REFERENCES 
56 
25.0 
APPENDICES 
58 
APPENDIX 25.1 REQUIRED STUDY PROCEDURES 
59 
APPENDIX 25.2 RESCUE STUDY ANTICOAGULATION SCENARIOS 
60 
APPENDIX 25.3 INFORMED CONSENT FORM 
61 
APPENDIX 25.4 CASE REPORT FORM 
62 
APPENDIX 25.5 CORE LAB PROTOCOLS 
63 
APPENDIX 25.6 COVID-19 CONTINGENCY PLAN 
64 
APPENDIX 25.7 RISK OVERVIEW 
68 
 
 
 


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Protocol THRO-CLIN-2019-01 Version  4.0         August 18, 2020          Page 5 of 74 
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part without written permission from Thrombolex, Inc. 
1.0  
PROTOCOL SYNOPSIS 
STUDY NAME 
Recombinant tPA by Endovascular Administration for the treatment of 
Submassive pulmonary embolism using pharmaco-mechanical Catheter 
directed thrombolysis for the redUction of thrombus burdEn - The RESCUE 
Study 
PROTOCOL NO. 
THRO-CLIN-2019-01 
PROTOCOL DATE 
August 18, 2020 
SPONSOR 
Thrombolex, Inc.  
STEERING 
COMMITTEE 
Anthony J. Comerota MD, FACS, FACC 
Kenneth Rosenfield MD, MSCAI, FACC 
Akhilesh K. Sista MD, FSIR, FAHA 
Victor Tapson MD, FCCP, FRCP 
STUDY DEVICE 
The Bashir™ Endovascular Catheter (BEC) is a device intended for the 
localized infusion of therapeutic agents into the pulmonary artery and 
peripheral vasculature. Two sizes of BECs will be used in this study.    
STUDY OBJECTIVE 
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. 
POPULATION 
Patients 18 to ≤ 75 years of age who present with symptoms of acute 
submassive PE within 14 days of onset of symptoms will be considered for 
this study.  
STUDY DESIGN 
Prospective, non-randomized, multi-center study. 
SAMPLE SIZE 
Up to 125 will be enrolled and treated; the subjects enrolled and treated per 
site will not exceed 20 subjects. 
SITES 
Up to 20 sites will be qualified to participate in this study.  
THROMBOLYTIC 
ADMINISTRATION 
Pulse Sprays:  
r-tPA 2mg in 20cc 0.9% NaCl divided into two (2) 10cc syringes to administer 
in two (2) pulse sprays, 10cc each, through the infusion port with 10cc 
syringes.  
Unilateral PE: 2mg total in 20cc administered in two (2) 10cc syringes. 
Bilateral PE: 4mg total in 40cc administered in two (2) 10cc syringes into each 
PA for a total of four (4) syringes, two (2) into each PA. 
Infusion:  
Unilateral PE: r-tPA 5mg in 500cc 0.9% NaCl infused at 1.00mg/hr at an 
infusion rate of 100cc/hr, through the Bashir™ Endovascular Catheter until r-
tPA mixture has completely infused. Total r-tPA dose (pulse spray and 
infusion) is 7mg. 
Bilateral PE: r-tPA 5mg in 500cc 0.9% NaCl infused at 1.00mg/hr at an 
infusion rate of 100cc/hr bilaterally through each Bashir™ Endovascular 
Catheter, until r-tPA mixture has completely infused, for a total r-tPA dose of 
1.0mg/hr through each catheter. Total r-tPA dose (pulse spray and infusion) 
for bilateral dosing is 14mg. 
 
 
 
 
 


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Protocol THRO-CLIN-2019-01 Version  4.0         August 18, 2020          Page 6 of 74 
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part without written permission from Thrombolex, Inc. 
1.0 PROTOCOL SYNOPSIS (CONTINUED) 
ANTICOAGULANT 
DOSAGE AND 
ADMINISTRATION 
Pre-procedure: There is a choice of anticoagulation to be administered 
according to the investigator’s standard of care.   
1. If the investigator’s standard of care is to use heparin, unfractionated 
heparin (UFH) will be administered by IV infusion to maintain therapeutic 
anticoagulation.   
2. If the administration of low molecular weight heparin (LMWH), such as 
enoxaparin (Lovenox®), is the investigator’s standard of care, administer 
1mg/kg sub-Q every 12 hours. 
BEC Procedure: Choose one of the two scenarios below according to the 
investigator’s standard of care:  
1. If heparin was administered pre-procedure or patient received LMWH 
1mg/kg SQ >12 hours prior to the BEC procedure, start BEC procedure 
with subject on heparin infusion in the IR suite / cath lab. Once r-tPA 
infusion is started, decrease heparin infusion dose to five (5) to eight (8) 
units/kg/hr up to a maximum of 1,000 units/hr. 
2. If LMWH was administered ≤ 12 hours pre-procedure, start BEC procedure 
without heparin in the IR suite / cath lab, until patient is 8 hours post last 
dose of LMWH. Then start infusion of UFH at five (5) to eight (8)  
units/kg/hr up to a maximum of 1,000 units/hr.   
Post-BEC Procedure: Heparin infusion at the completion of the BEC 
procedure and during the r-tPA infusion: 
1. Continue heparin administration through the side arm of the sheath at five 
(5) to eight (8) units/kg/hr up to a maximum of 1,000 units/hr.  If bilateral 
BECs are in place, the heparin infusions must be administered into each 
sheath.  Administer half (or approximately half) the dose prescribed by the 
investigator into the side arm of each sheath to equal the prescribed dose. 
2. If subject has not reached 8 hours post last dose of LMWH in the IR suite 
/ cath lab, then in the ICU start dose of UFH at five (5) to eight (8)  
units/kg/hr up to a maximum of 1,000 units/hr. 
Post r-tPA Infusion: Once r-tPA infusion is complete, increase UFH dose to 
target aPTT within therapeutic range (aPTT suggested 60-80 sec). Replace r-
tPA infusion with standard heparinized saline through the basket infusion line 
connector of the BEC(s) at 30cc/hour to maintain patency until removal.  
Sheath Removal: Stop UFH for at least one (1) hour prior to sheath removal, 
unless the operator believes that the UFH, in the best interest of the patient, 
should not be stopped prior to and during sheath removal.  Remove sheaths 
according to standard of care. 
Anticoagulation Post-Sheath Removal: Re-start anticoagulation within one 
(1) hour post sheath removal with LMWH 1mg/kg SQ q 12 hours or UFH at 
therapeutic doses for 24 hours post sheath removal.  After 24 hours post sheath 
removal, physicians can start therapeutic anticoagulation according to their 
standard of care. If physicians choose to use DOACs then patients should be 
properly loaded according to the current guidelines. 
 
 
 


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Protocol THRO-CLIN-2019-01 Version  4.0         August 18, 2020          Page 7 of 74 
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part without written permission from Thrombolex, Inc. 
1.0 PROTOCOL SYNOPSIS (CONTINUED) 
PRIMARY 
EFFICACY 
ENDPOINT 
1. Reduction in RV/LV diameter ratio as measured by contrast enhanced 
chest CT (CTA) within 48 hours after the completion of r-tPA treatment.  
PRIMARY SAFETY 
ENDPOINT 
1. 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 study subjects is defined as having a 
symptomatic presentation and:  
a. 
Fatal bleeding; and/or  
b. 
Bleeding in a critical area or organ, such as intracranial, intraspinal, 
intraocular, 
retroperitoneal, 
intraarticular 
or 
pericardial, 
or 
intramuscular with compartment syndrome; and/or 
c. 
Bleeding causing a fall in hemoglobin level of 2.0g/dL (1.24 
mmol/L) or more or leading to transfusion of two or more units of 
whole blood or red cells. 
SECONDARY 
ENDPOINTS 
1. Device Success: The number of devices with therapy delivered without a 
device failure.  
2. Refined Modified Miller Score as measured on contrast enhanced chest 
CT (CTA) within 48 hours after the completion of the r-tPA infusion 
compared to baseline as measured by core lab. 
3. All-cause mortality at hospital discharge through 30-day follow-up. 
4. SAEs through 30-day follow-up. 
5. AEs through 30-day follow-up. 
6. UADEs through 30-day follow-up. 
7. Recurrent PE through 30-day follow-up.  
8. 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:  
a. Requiring medical intervention by a healthcare professional.  
b. Leading to hospitalization or increased level of care.  
c. Prompting a face to face (i.e., not just a telephone or electronic 
communication) evaluation.  
9. Technical procedural complications. 
10. Systolic PA pressure measured at completion of infusion after BEC(s) 
removal and compared to baseline. 
11. Cardiac output (CO by Modified Fick calculation) and cardiac index (CI) 
following completion of the r-tPA infusion 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 the ICU 
after BEC removal).                           
 
 
 


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part without written permission from Thrombolex, Inc. 
1.0 PROTOCOL SYNOPSIS (CONTINUED) 
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 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; 
Continued next page 


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part without written permission from Thrombolex, Inc. 
1.0 PROTOCOL SYNOPSIS (CONTINUED) 
ELIGIBILITY 
CRITERIA 
(CONTINUED) 
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. 
SUBJECT 
PARTICIPATION 
Duration of participation will be from time of informed consent through 30-
day follow-up. 
STUDY DURATION 
It is estimated that the study duration will be 24 months. 
CEC/DSMB 
CHAIRPERSON 
Gregory Piazza, MD, MS 
Brigham and Women’s Hospital  
Boston, MA 
STUDY 
MANAGEMENT 
Eminence Clinical Research, Inc. 
13521 Northgate Estates Drive 
Suite 150 
Colorado Springs, CO 80921 
DATA 
MONITORING 
EDC 
CTA 
INDEPENDENT 
CORE LAB 
Syntactx, LLC 
Richard Ouriel  
SVP, Clinical Services  
4 World Trade Center 
150 Greenwich Street, Floor 44 
New York, NY 10007  
Phone: 212-878-6885 
Email: rouriel@syntactx.com 
 
 


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part without written permission from Thrombolex, Inc. 
2.0 STUDY CONTACTS 
Vascular Surgeon 
Interventional Cardiologist 
 
 
Anthony J. Comerota MD, FACC, FACS 
Kenneth Rosenfield MD, MSCAI, FACC 
Inova Alexandria Hospital 
Massachusetts General Hospital  
4320 Seminary Road 
 55 Fruit St. #800 
Alexandria, VA 22304 
Boston, MA 02114 
Phone: 703-504-7760 
Phone: 617-726-2256 
Email: anthonyjcomerota@gmail.com 
Email: krosenfield1@mgh.harvard.edu 
Interventional Radiologist 
Internal Medicine / Pulmonary Medicine 
 
 
Akhilesh K. Sista MD, FSIR, FAHA  
Victor Tapson MD, FCCP, FRCP 
NYU Langone I 
127 South San Vincente Blvd 
660 1st Avenue Room 318  
Suite 3600 
New York, NY 10016 
Los Angeles, CA 90048 
Phone: 212-746-2771 
Phone: 310-423-2747 
Email: asista@gmail.com 
Email: victor.tapson@cshs.org 
STUDY MANAGEMENT / INDEPENDENT CORE LAB 
 
 
Eminence Clinical Research, Inc. 
Syntactx, LLC 
Christopher A. Schultz, BS, CCRA, ACRP-PM 
Richard Ouriel SVP, Clinical Services  
13521 Northgate Estates Drive, Suite 150 
4 World Trade Center 
Colorado Springs, CO 80921 
150 Greenwich Street, Floor 44 
Phone:  719-400-7463 
New York, NY 10007 
e-Fax: 720-206-0985 
Phone: 212-878-6885 
Email: cschultz@ecr-inc.com 
Email: rouriel@syntactx.com 
 
 
 


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part without written permission from Thrombolex, Inc. 
3.0 TERMS AND DEFINITIONS 
TERM 
DEFINITION 
AE 
Adverse Event  
aPTT 
Activated partial thromboplastin time 
BEC 
Bashir™ Endovascular Catheter 
BNP 
Brain Natriuretic Peptide is made inside the pumping chambers of the heart 
when pressure builds up from heart failure. The test is an important 
assessment to diagnose heart failure quickly.  
BSA 
0.024265 X (Height in cm)0.3964 X (Weight in kg)0.5378   
CBC  
Complete blood count 
CEC 
Clinical events committee 
CFV 
Common femoral vein 
CI 
Cardiac Index:  Hemodynamic parameter that relates the cardiac output (CO) 
from right or left ventricle in one minute to body surface area (BSA), thus 
relating heart performance to the size of the individual. The unit of 
measurement is liters per minute per square meter (L/min/m2).  CI = CO/BSA. 
CO 
Cardiac output 
COVID-19 
Novel Coronavirus Disease 2019  
CMP 
Complete metabolic panel 
CTA 
Computerized tomography angiography 
CTEPH 
Chronic thromboembolic pulmonary hypertension 
CVA 
Cerebrovascular accident 
DOAC 
Direct-Acting Oral Anticoagulant 
DSMB 
Data safety monitor board: Panel of physicians experienced in the treatment 
of PE with mechanical thrombolysis will review all adverse events in this 
study. 
DUS 
Duplex ultrasound - a type of ultrasound used to visualize the vasculature. 
This is a study requirement to assess the ability to access the PA(s) from the 
CFV. 
F2F 
Face-to-face 
GTT 
Drip 
Modified Fick 
Calculation 
CO = O2 Consumption (VO2) ml/min = L/min 
          (CaO2 – CvO2) x 10 
VO2 = 125 x BSA 
CaO2 = (1.36 x Hgb x SpO2) 
CvO2 = (1.36 x Hgb x SvO2) 
This Modified Fick calculation is required in this protocol. Substitute CaO2 
with SpO2 as indicated above to eliminate the need for an arterial puncture.  


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3.0 TERMS AND DEFINITIONS (CONTINUED) 
TERM 
DEFINITION 
HIT 
Heparin induced thrombocytopenia 
Hr 
Hour 
Hrs 
Hours 
IJ 
Internal jugular 
INR 
International normalized ratio 
LCFV 
Left common femoral vein 
LMWH 
Low molecular weight heparin 
NOAC 
Non-vitamin K oral anticoagulants; such as rivaroxaban (Xarelto®), apixaban 
(Eliquis®), dabigatran (Pradaxa®), edoxaban (Savaysa®). 
PAD 
Pulmonary artery diastolic pressure 
PaO2 
Partial pressure of arterial oxygen 
PAP 
Pulmonary artery pressure 
PAS (PASP) 
Pulmonary artery systolic pressure 
PE 
Pulmonary embolism 
PMCDT 
Pharmaco-mechanical catheter directed thrombolysis 
Procedure Start 
Time 
Procedure start time refers to the PMCDT (BEC) procedure and is defined as 
the injection of local anesthetic at the access site prior to sheath placement in 
the IR suite / cath lab.   
RCFV 
Right common femoral vein 
Recurrent PE 
Recurrent PE is deﬁned as symptomatic and objectively conﬁrmed with 
contrast-enhanced chest CT or invasive contrast pulmonary angiography. 
Refined Modified 
Miller Score 
(RMMS) 
Like the Modified Miller (MM) score, the Refined Modified Miller score 
(RMMS) regards each lung as having 10 segmental arteries, and the degree 
of obstruction of the segmental pulmonary arteries is measured using an 
ordinal scale. In contrast to the MM, however, the RM score allows for a ﬁner 
distinction of partial obstruction in seven major arteries; the main pulmonary 
artery, left and right pulmonary artery, left and right interlobar arteries, left 
and right basal trunks. Partial obstruction is classiﬁed into three categories 
based upon cross-sectional diameter reduction: 0.5 for 1–33%, 1.0 for 34–
66%, and 1.5 for 67–99% obstruction. As in the MM scoring system, the 
weighted score of the major supplying artery is compared with the sum of its 
tributaries, and the larger number is recorded. For example, if thrombus 
obstructed the lumen of a basal trunk vessel by 50% (score =1.0 x 7), but its 
four segmental tributaries were fully occluded (score = 2.0 x 4), the higher 
value of 8 would be recorded as the RMM score. A cumulative score is 
calculated by summing the scores for all arteries. Similar to the MM score, 
the RMM score can range from 0 to 20 per lung, for a maximum of 40 
bilaterally.25 
 
 


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3.0 TERMS AND DEFINITIONS (CONTINUED) 
TERM 
DEFINITION 
RV/LV 
Right ventricular / left ventricular 
SAE 
An adverse event is any undesirable experience associated with the use of a 
medical product in a patient. The event is serious and will be collected when 
the patient outcome is: 
Death 
Life-threatening - Report if suspected that the patient was at substantial risk 
of dying at the time of the adverse event or use or continued use of the device 
or other medical product might have resulted in the death of the patient. 
Hospitalization (initial or prolonged) - Report if admission to the hospital 
or prolongation of hospitalization was a result of the adverse event. 
Emergency room visits that do not result in admission to the hospital should 
be evaluated for one of the other serious outcomes (e.g., life-threatening; 
required intervention to prevent permanent impairment or damage; other 
serious medically important event). 
Disability or Permanent Damage - Report if the adverse event resulted in 
a substantial disruption of a person's ability to conduct normal life functions, 
i.e., the adverse event resulted in a significant, persistent or permanent 
change, impairment, damage or disruption in the patient's body 
function/structure, physical activities and/or quality of life. 
Congenital Anomaly/Birth Defect - Report if you suspect that exposure to 
a medical product prior to conception or during pregnancy may have resulted 
in an adverse outcome in the child. 
Required Intervention to Prevent Permanent Impairment or Damage 
(Devices) - Report if you believe that medical or surgical intervention was 
necessary to preclude permanent impairment of a body function, or prevent 
permanent damage to a body structure, either situation suspected to be due to 
the use of a medical product. 
Other Serious (Important Medical Events) - Report when the event does 
not fit the other outcomes, but the event may jeopardize the patient and may 
require medical or surgical intervention (treatment) to prevent one of the 
other outcomes. Examples include allergic bronchospasm (a serious problem 
with breathing) requiring treatment in an emergency room, serious blood 
dyscrasias (blood disorders) or seizures/convulsions that do not result in 
hospitalization. The development of drug dependence or drug abuse would 
also be examples of important medical events. 
SaO2 
Arterial oxygen saturation 
SpO2 
Arterial oxygen saturation measured by pulse oximetry 
Submassive PE 
A normotensive patient with PE and evidence of RV dysfunction 
SvO2 
Venous oxygen saturation drawn from the pulmonary artery 
 


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3.0 TERMS AND DEFINITIONS (CONTINUED) 
TERM 
DEFINITION  
TIA 
Transient ischemic attack 
Troponin 
Cardiac troponins are the most sensitive and the most specific biochemical 
markers showing myocardial injury. Elevated troponin can also be seen in 
acute pericarditis, myocarditis, acute PE, severe cardiac failure, sepsis and 
acute renal failure as well as in myocardial infarction.  In acute PE, the 
mechanic load of the right ventricle is increased because of the increased 
pulmonary vascular resistance following pulmonary artery obstruction. That 
can lead to acute right ventricular dilatation. The dilatation and hypokinesia 
of the right ventricle may cause severe myocardial ischemia and increase the 
troponin levels. Increased serum Troponin levels support the diagnosis of 
severe PE.  
UADE 
According to 21 CFR 812.3(s) an unanticipated adverse device effect means 
any serious adverse effect on health or safety of any life-threatening problem 
or death caused by, or associated with, a device if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence 
in the investigational plan or application(including a supplementary plan or 
application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects.   
UFH 
Unfractionated heparin 
USAT 
Ultrasound assisted thrombolysis 
VTE  
Venous thromboembolism - a disease that includes deep vein thrombosis 
(DVT) and pulmonary embolism (PE).  
 
 
 


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4.0 BACKGROUND AND RATIONALE 
4.1 
Clinical Problem   
Acute venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and acute 
pulmonary embolism (PE). PE occurs when a deep vein thrombus breaks loose and embolizes 
to the pulmonary artery. Pulmonary embolism is the third leading cause of cardiovascular death 
after myocardial infarction and stroke and is a major global health problem.1,2    
 
Raskob et al (2014) conducted a literature search and review and found that there is a strong and 
consistent association between an increase in incidence of VTE and increasing age. They found 
the annual incidence increased from between 2 and 7 per 1,000 population for those 79 and 
younger to between 3 and 12 per 1,000 population for those aged 80 and older.  This finding has 
major implications for the treatment of the elderly in the US healthcare system.2 It is important 
to note that 60 percent of the VTE events are associated with hospitalization.3 The number of 
deaths from VTE in the USA has previously been reported to be approximately 300,000 
annually.3,4 Clinically, study subjects may present with DVT or PE, or both.  With many of the 
known risk factors, advanced age, immobility, surgery, obesity, increasing in our society, this 
number only continues to grow.  Because there is no national surveillance program for VTE, the 
precise number with VTE of all types is unknown.5,6 
 
Patients who present with PE may be classified into low risk, intermediate risk (submassive) or 
high risk (massive) PE. Both massive and submassive PE cause right ventricular (RV) 
dysfunction, while massive PE in addition causes systemic hypotension.  Typical diagnostic 
studies include contrast enhanced computerized tomography (CT) to diagnose the PE, 
echocardiography to assess right and left ventricular function, and cardiac biomarkers, such as 
troponin I, and BNP to assess the degree of myocardial ischemia/strain associated with the PE.  
Patients categorized as having a low-risk PE do not have evidence of hemodynamic compromise 
or RV dysfunction.  Low risk PE patients are not included in this study for obvious reasons.7 
4.2 
Current Treatment Options   
Anticoagulant therapies are administered to symptomatic patients while their workups are being 
completed for a definitive diagnosis of massive or submassive PE.  For the treatment of massive 
and submassive PE, both systemic administration and catheter-directed administration of 
thrombolytic therapies have been utilized.8-10 However, systemic administration of 
thrombolytics carries a prohibitively high risk of bleeding: Up to 7% intracranial bleeds and up 
to 20% major bleeding rates; hence the attraction of delivering thrombolytics in much lower 
dosage directly into the clot to treat this potentially life-threatening condition.11   
Devices for percutaneous treatment of patients in whom systemic thrombolytic therapy is 
absolutely contraindicated have been developed and utilized.   The percutaneous devices include 
manual thrombus fragmentation using a balloon dilatation catheter or a pigtail (off-the shelf 
technologies). More recently, catheters specifically created for thrombus fragmentation that 
produce greater fragmentation of the clot compared to off-the-shelf technologies mentioned 


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previously, without aspirating the clot; aspiration or suction thrombectomy devices to decrease 
thrombus burden; rheolytic thrombectomy where a saline jet is directed into the clot and the clot 
and saline are aspirated, have been introduced.7-10,12-14  However, there are also hazards 
associated with rapid clot fragmentation including hemodynamic collapse   due to the distal 
embolization of thrombus and release of vasoactive substances.     
Over the past several years a device received 510(k) clearance for its ultrasound-facilitated, 
catheter directed low-dose fibrinolysis using r-tPA (EKOS, Bothell WA). With this technology, 
the EKOS ultrasound device was used to deliver t-PA in patients with massive and submassive 
PE at 1mg/hour over 24 hours (unilateral PE), and 2mg/hr over 12 hours (bilateral PE).15  
More recently, studies have reported that the ultrasound component of the EKOS device does 
not contribute to the effectiveness of the treatment of submassive and massive pulmonary 
embolism.  Kuo et al (2015) found in a real-world registry, for CDT that incorporated USAT, 
there was no advantage in patients treated with USAT vs standard CDT. These data suggest that 
CDT may be performed effectively without the added cost associated with USAT.16 In a 
subgroup analysis comparing patients treated with EKOS to those treated with standard infusion 
catheters, Bloomer et al (2017) reported a study for the Safety of CDT for massive and 
submassive PE: Results of a multi-center registry and Meta-analysis. Bloomer et al found in a 
subgroup analysis comparing patients treated with EKOS to those treated with standard infusion 
catheters, that there were similar PA pressure changes after CDT and similar complication rates. 
CDT is associated with a low major complication rate.17  
Tafur et al (2016) conducted a Systematic Review and Meta-Analysis of Modern Literature. 
They concluded from their study current clinical evidence does not show that USAT is superior 
to other CDT methods.18   
Overall, CDT decreased PASP, decreased RV to LV diameter ratio, and reduced the Modified 
Miller Index scores.  The goal of CDT is to substantially reduce thrombus burden, as assessed 
by the Modified Miller Index on CTA, which remains high with currently available catheters, 
with or without USAT.   
While it is critical to reduce RV/LV ratio, it is of great importance to both short-term and long-
term patient outcomes to decrease the thrombus burden as much as is feasible.  Even a small 
reduction in the clot burden can translate into a marked improvement in RV function and 
improve acute survival. However, much more effective reduction in the residual clot burden is 
required to reduce the long-term complications of PE, including disabling post-PE syndrome 
and chronic thromboembolic pulmonary hypertension (CTEPH).7   
4.3 
Study Rationale 
While the medical community continues to focus on prevention of VTE, half of all VTE patients 
have unprovoked VTE. Therefore, the treatment options for patients who present with DVT 
and/or acute PE must continue to evolve to increase efficacy, decrease side effects, limit long-
term complications, and provide an improved quality of life for these patients. This study is 
focused on the treatment of patients with acute submassive PE with an interventional device 
designed to increase the exposure of the thrombus burden to endogenous and exogenous 


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thrombolytics, thus this increased exposure has the potential to greatly decrease the thrombus 
burden.  
 
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).19 The dosing of the thrombolytic 
in the past has been much greater than what is proposed in this study.  The SEATTLE II study 
administered a total of 24 mg of r-tPA over 12 hours for bilateral PE and 24mg over 24 hours 
for unilateral PE.  The incidence of major bleeding in the SEATTLE II study was 10 percent.20  
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.  
 
Because of the rationale stated previously, a reduced dose of thrombolytic can be administered 
over a reduced period of time due to an increased exposure of the clot to endogenous and 
exogenous thrombolytics for clot dissolution.  The OPTALYSE study, using the EKOS catheter, 
was conducted to assess the outcomes with lower dose r-tPA administration for the treatment of 
acute submassive PE. Four groups were administered lower doses of r-tPA over a shorter period 
of time.  While each group showed a statistically significant reduction in RV/LV ratio at 48 
hours post-procedure, the reduction in residual clot burden was noticeably lower (6%) in patients 
treated with the smallest dose of r- tPA for the shortest time period (4/8 mg r-tPA over 2 hours) 
compared to those treated with the highest dose for the longest duration (26% reduction in clot 
burden; 12/24 mg r-tPA over 6 hours). This illustrates the discordance between reduction in 
RV/LV diameter ratio and reduction in clot burden, as well as a dose response relationship. 
between the dose of r-tPA administered and the reduction in clot burden.30 It is much easier to 
achieve the former than the latter with low doses of r-tPA for shorter periods of time. There is 
clearly also a lot of room for improvement if 74% of the clot burden still remains after the 
highest dose of infusion in the OPTALYSE study.21  
 


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We hypothesize that the dose of r-tPA may be reduced using the Bashir™ Endovascular 
Catheter from what was administered in the SEATTLE II study, i.e. 24mg over 12 hours 
(bilateral PE) or 24 hours (unilateral PE), because of its unique features described previously, 
as well as our experience in the First- in-Man study just completed with the BEC in patient with 
acute submassive pulmonary embolism (see below).20 We therefore propose to utilize the 
following regimen: r-tPA 2mg in 20cc administered,  1.0mg in two 10cc increments  into the 
PA for a total of 2 pulse sprays into the infusion basket.  This will be done for each PA if the 
subject has bilateral pulmonary embolisms. The pulse sprays will be followed by a 5mg infusion 
at 1.00mg/hr until complete for unilateral PE, and 5mg infusion into each pulmonary artery for 
bilateral PE, at 1.0mg/hr until complete.  This is a total of 10.0mg over approximately five hours 
(pulse spray 1.0mg x 2 sprays = 2mg plus infusion at 1.0mg/hr x 5 hours = 7mg for unilateral 
PE). For bilateral PE, we propose to administer the same pulse spray and same infusion dose 
into each PA for a total of 14mg administered.  This is a substantially lower dose and a shorter 
duration of treatment compared to SEATTLE II for the treatment of PE in a similar patient 
cohort.   
4.4 
First-in-Man Study Results 
The first-in-man study has been completed.  Nine subjects were enrolled, treated, and followed 
through 30-day follow-up.  Patients received 2 X 1mg pulse sprays of r-tPA into each affected 
pulmonary artery followed by a total of 10mg r-tPA over 8 hours. The total dose of r-tPA for 
unilateral PE was thus 12mg and for bilateral PE 14mg.  Through 30-day follow-up there were 
no deaths, BEC or r-tPA related major bleeding, or device related adverse events. After 48 hours 
the RV/LV ratio decreased from 1.52  0.26 to 0.97  0.06 (p = .0009: 95% CI = 0.33 to 0.82: 
36.7% reduction) as assessed by an independent core lab (Medical Metrics, Houston, TX). 
Thrombus burden measured by Modified Miller Index as assessed by the independent core lab 
(Medical Metrics, Houston, TX) decreased from 25.4  5.3 to 16.0  4.0 (p = .0005: 95% CI = 
5.5 to 13.4: 37.1% reduction). BEC CDT appears safe, preliminary evidence shows that this 
platform technology leads to significant reduction in RV/LV ratio and thrombus burden.  The 
study protocol permitted to enroll up to ten (10) subjects.  The sponsor stopped enrollment on 
December 3, 2019 due to the consistent results shown across the sites after nine (9) subjects 
were enrolled. 
5.0 INVESTIGATIONAL DEVICE 
The Bashir™ Endovascular Catheter (BEC) and the BEC Short Basket (S-B) are devices intended for 
the localized infusion of therapeutic agents into the pulmonary artery and peripheral vasculature. The 
distal infusion segment of the device contains an expandable radial array of conduits with a total of 48 
laser drilled orifices used for the delivery of the therapeutic agents at multiple cross-sectional points of 
the target vessel location. The infusion segment can be expanded and collapsed by the actuator (slider) 
located on the handle at the proximal end of the device. The infusion line connector is also located on 
the handle.22 The difference between the BEC and the BEC S-B is solely in the length of the basket. In 
its unexpanded state, the basket of the BEC 12.5cm long and the BEC S-B basket is 10cm long. The 
choice of device used will be at the physician’s discretion based on the patient’s anatomy.    
 


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Figure 1. Bashir Endovascular Catheter 
  
 
 
Figure 2. Bashir Endovascular Catheter with Basket Expanded 
 
Table 1. Bashir™ Endovascular Catheter Dimensions 
Bashir Endovascular Catheter 
French Size 
7F (2.3mm) 
Effective Length 
92.5cm (36.44 in) 
Infusion Segment Length 
12.50cm (4.94 in) 
Infusion Basket Diameter 
45mm Maximum 
Bashir Endovascular Catheter Basket Length Unexpanded 
12.50cm 
 
 
Bashir Endovascular Catheter – Short Basket 
French Size 
7F (2.3mm) 
Effective Length 
92.5cm (36.44 in) 
Infusion Segment Length 
10.0cm (3.94 in) 
Infusion Basket Diameter 
42mm Maximum 
Bashir Endovascular Catheter Short Basket Length Unexpanded 
10.0cm 


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6.0 STUDY DESIGN 
6.1 
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 using low 
dose r-tPA for the treatment of acute submassive pulmonary embolism. 
6.2 
Endpoints 
6.2.1 
Primary Efficacy Endpoint 
Reduction in RV/LV diameter ratio as measured by CTA within 48 hours after the 
completion of r-tPA treatment.  
6.2.2 
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, intraarticular 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.27 
6.2.3 
Secondary Endpoints 
1. Device Success: The number of devices with therapy delivered without a 
device failure.  
2. 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 
3. All-cause mortality at hospital discharge through 30-day follow-up. 
4. SAEs through 30-day follow-up. 
5. AEs through 30-day follow-up. 
6. UADEs through 30-day follow-up. 
7. Recurrent PE through 30-day follow-up.  
8. 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:  
a. Requiring medical intervention by a healthcare professional.  
b. Leading to hospitalization or increased level of care.  


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c. Prompting a face to face (i.e., not just a telephone or electronic 
communication) evaluation. 27  
9. Technical procedural complications. 
10. Systolic PA pressure measured at completion of infusion after BEC(s) 
removal and compared to baseline. 
11. Cardiac output (CO by Modified Fick calculation) and cardiac index (CI) 
following completion of the r-tPA infusion 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 the ICU after BEC 
removal). 
6.3 
Eligibility Criteria 
The population to be enrolled in this study includes patients 18 to 75 years of age who 
present with symptoms of acute submassive PE within 14 days of onset of symptoms 
will be considered for this study.   
6.3.1 
General Inclusion Criteria 
All answers must be YES to the inclusion criteria below: 
1. Willing and able to provide informed consent; 
2. Age 18 years of age to ≤ 75 years of age; 
3. PE symptom duration ≤ 14 days; 
4. Filling defect on at least one main or lobar pulmonary artery as determined 
on 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. 
6.3.2 
General Exclusion Criteria 
All answers must be NO to the exclusion criteria below: 
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;  


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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. Subject is 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. 
6.4 Study Duration 
6.4.1 
Enrollment 
It is estimated that up to 20 sites will be qualified to participate; they will enroll 
and treat up to 125 subjects (to achieve 100 evaluable subjects) over an estimate 
of 24 months.  There may be an unlimited number of subjects consented for this 
study to achieve completion of 100 evaluable subjects.  A maximum of 125 
subjects will be enrolled, treated, and complete the study through 30-day 
follow-up. The subjects enrolled and treated per site will not exceed 20 subjects. 


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6.4.2 
COVID-19 Impact Assessment Form - Enrollment  
A COVID-19 Impact Assessment Form will be completed to assess if study 
investigators and other site personnel are unable to be on site to manage 
enrollment, and having subjects at the institution places them at risk, and if there 
is a known risk that follow up may not occur as planned.  This form shall be 
submitted to the CRO as soon as possible. The CRO will review the Impact 
Assessment Form with Thrombolex Inc. and communicate an appropriate plan 
according to the site’s level of operation. Enrollment will be suspended if a site 
cannot enroll in accordance with the study protocol. All actions regarding 
suspension and activation will be documented. The site IRB will be sent all 
related communications.  
The implementation of alternative processes should be consistent with the 
protocol to the extent possible, and sponsors and clinical investigators should 
document the reason for any contingency measures implemented. Sponsors and 
clinical investigators should document how restrictions related to COVID-19 
led to the changes in study conduct and duration of those changes and indicate 
which trial participants were impacted and how those trial participants were 
impacted. 
6.4.3 
Follow-up 
The follow-up for each subject will be completed at 30-days post-hospital 
discharge.  
6.4.4 
COVID-19 Impact Assessment Form - Follow-Up Visits 
The COVID-19 Impact Assessment Form identifies aspects of the follow-up 
visits that can be completed and how (i.e. via telephone, or video conference). 
The CRO will review the Impact Assessment Form with Thrombolex, Inc. and 
generate site specific follow-up protocols to be implemented. This will ensure 
that alternate follow-up visit plans are consistent for the site and in accordance 
with the COVID-19 Impact Assessment. The COVID-19 Impact Assessment 
Form, if completed by site(s) due to necessary changes in study conduct, the 
changes will be in effect until clinical research operations are restored.   
All actions related to COVID-19 will be documented. If a follow-up visit under 
the COVID-19 does not meet protocol requirements, the visit will be reported 
as a protocol deviation and tracking of visits where protocol requirements 
cannot be met conducted under COVID-19 will be documented. 
The implementation of alternative processes should be consistent with the 
protocol to the extent possible, and sponsors and clinical investigators should 
document the reason for any contingency measures implemented. Sponsors and 
clinical investigators should document how restrictions related to COVID-19 
led to the changes in study conduct and duration of those changes and indicate 


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which trial participants were impacted and how those trial participants were 
impacted. 
6.4.5 
Complete Study Period 
It is estimated that this study will require up to 24 months to complete 
enrollment and follow-up. 
6.4.6 
Subject Participation 
Each subject will participate in this study for approximately 30 days from 
consent through 30-day follow-up. 
7.0 METHODOLOGY 
7.1 Pre-Procedure Testing Within 48 Hours Pre-Procedure 
7.1.1 
Laboratory Tests 
1. CMP, CBC, Cardiac Biomarkers Troponin and BNP – These tests will 
be drawn within 48 hours pre-procedure. 
2. aPTT – Drawn within 48 hours pre-procedure. If the investigator’s 
standard of care is to use heparin, unfractionated heparin will be 
administered, and aPTT is to be drawn prior to the BEC procedure.   
3.  International Normalized Ratio (INR) – INR will be drawn within 48 
hours pre-procedure for patients who are on warfarin (Coumadin®) and 
must be ≤ 1.5 to be eligible for enrollment.  Patients who are on warfarin 
who have consented for the study and have an INR ≤ 1.5, warfarin will be 
discontinued during the heparin infusion and the r-tPA infusion and 
restarted prior to hospital discharge. 
7.1.2 
Imaging 
1. Contrast Enhanced CT of Chest (CTA) – A chest CTA will be performed 
within 48 hours pre-procedure.  The CTA is used to determine the pre-
procedure Refined Miller Score by core lab analysis.  The CTA will be used 
by the study site to determine eligibility into the study ensuring the RV/LV 
diameter ratio is ≥ 0.9 by CTA.  CTA will be sent to the core lab for 
analysis. 25 
 
2. Lower Extremity Venous DUS – A duplex ultrasound is required within 
48 hours pre-procedure to verify patency of the common femoral vein 
(CFV) for femoral access.  The right CFV or the left CFV may be used for 
access, whichever is patent.  If both of the CFVs are not patent, an internal 
jugular (IJ) vein may be used for access.  IJ may also be used if that is the 
operator’s preference. 


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7.1.3 
Assessments 
1. Physical Examination – The physician will perform a physical exam 
within 48 hours prior to the procedure to ensure the subject meets eligibility 
criteria. 
 
2. RV/LV Diameter Ratio – The RV/LV ratio will be measured within 48 
hours pre-procedure by CTA to ensure the subject meets the eligibility 
criteria of an axial RV/LV ratio ≥ 0.9, as determined by the investigative 
site.  The independent core lab protocol will be followed for data 
acquisition. The CTA will be sent to the core lab for analyses. 
 
3. 12-Lead Electrocardiogram (ECG) – A 12-lead ECG will be performed 
prior to the procedure. 
7.1.4 
Anticoagulation 
Pre-procedure: There is a choice of anticoagulation to be administered 
according to the investigator’s standard of care.  
1. If the investigator’s standard of care is to use heparin, unfractionated 
heparin (UFH) will be administered by IV infusion to maintain therapeutic 
anticoagulation. 
2. If the administration of LMWH, such as enoxaparin (Lovenox®), is the 
investigator’s standard of care, administer 1mg/kg sub-Q every 12 hours. 
BEC Procedure: Choose one of the two scenarios below according to the 
investigator’s standard of care:  
1. If heparin was administered pre-procedure or patient received LMWH 
1mg/kg SQ >12 hours prior to the BEC procedure, start BEC procedure 
with subject on heparin infusion in the IR suite / cath lab.  Once r-tPA 
infusion is started, decrease dose of heparin to five (5) to eight (8) 
units/kg/hr up to a maximum of 1,000 units/hr. ACTs may be checked if 
standard of care. 
2. If LMWH was administered pre-procedure, start BEC procedure without 
heparin in the IR suite / cath lab, until patient is 8 hours post last dose of 
LMWH.  Then start dose of UFH at five (5) to eight (8) units/kg/hr up to a 
maximum of 1,000 units/hr. ACTs may be checked if standard of care. 
 
Post-BEC Procedure: Heparin infusion at the completion of the BEC 
procedure and during the r-tPA infusion: 
1. Continue heparin administration through the side arm of the sheath at five 
(5) to eight (8) units/kg/hr up to a maximum of 1,000 units/hr.  If bilateral 
BECs are in place, then one-half of the dose of the heparin infusion must 
be administered into each sheath for a total prescribed dose.  Administer 
half (or approximately half) the dose prescribed by the investigator into the 
side arm of each sheath to equal the prescribed dose. 


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2. If subject has not reached 8hrs post last dose of LMWH in the IR suite / 
cath lab, then in the ICU start dose of UFH at five (5) to eight (8) units/kg/hr 
up to a maximum of 1,000 units/hr. 
 
Post r-tPA Infusion: Once r-tPA infusion is complete, increase UFH dose to 
keep aPTT within therapeutic range (aPTT suggested 60-80 sec).  Replace r-
tPA infusion with standard heparinized saline at 30cc/hr on an infusion pump 
through the basket infusion line connector of the BEC(s) to maintain patency 
until removal of the BEC(s).   
 
Sheath Removal: Stop UFH for at least one (1) hour prior to sheath removal, 
unless the operator believes that the UFH, in the best interest of the patient, 
should not be stopped prior to and during sheath removal.  Remove sheaths 
according to standard of care. 
Anticoagulation Post-Sheath Removal: Re-start anticoagulation within one 
(1) hour post sheath removal with LMWH 1mg/kg SQ q12hrs or UFH at 
therapeutic doses for 24hrs post sheath removal.  After 24hrs post sheath 
removal, physicians can start therapeutic anticoagulation according to their 
standard of care.  If physicians choose to use DOACs then patients should be 
properly loaded according to the current guidelines. 
7.1.5 
Data Collection 
The following data will be collected and documented in the CRF in addition to 
the required pre-procedure testing. 
1. Informed Consent – Required for all study subjects prior to any testing 
that is not the standard of care. Please note that the screen failure rate is 
unknown for this study.  Patients may be consented until up to 125 subjects 
have been enrolled and treated per protocol. Therefore, more subjects will 
be consented than are treated in order to reach the minimum of 100 subjects 
included in the analysis.  The subjects enrolled and treated per site will not 
exceed 20 subjects. 
2. Demographics and Medical History – Recorded once Informed Consent 
has been obtained. 
3. Eligibility Criteria – All inclusion criteria must be met, and all exclusion 
criteria must not be met to enroll in this study. 
4. Medications – All antiplatelet, anticoagulant, cardiac meds, and NSAIDs 
will be recorded within 48 hours pre-procedure, at baseline. 
5. Refined Modified Miller Score (RMMS) – Refined Modified Miller 
Score (RMMS) will be calculated by the core lab at baseline. The CTA will 
be sent to the core lab for RMI analysis.25 


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8.0 IR SUITE / CATH LAB STUDY PROCEDURES   
Should the study subjects meet all eligibility criteria for inclusion into the study, continue with the 
following procedures that take place in the IR suite / cath lab.   
8.1 Required Accessories and Supplies 
8.1.1 
Accessories to be provided by the IR suite / cath lab 
1. Introducer Sheath(s) - 7F or greater and of appropriate length. The sheath 
selected must reach the target site and allow for retraction to expose the 
infusion basket. A 75cm length or less straight tip sheath, e.g. Flexor® 
Raabe Guiding Sheath (Cook Medical, Inc.) or equivalent for femoral 
access is recommended for most. The sheath length must be long enough 
to reach the clot and must not exceed 75cm.  A shorter sheath of 
appropriate length may be utilized for IJ access and the sheath used must 
be able to reach the clot. 
2. Ultrasound for ultrasound guided access is required for both IJ and CFV 
access. 
3. Micropuncture kit for IJ and CFV venous access is required for both IJ and 
CFV access. 
4. Guidewire - .018in x 300cm in length minimum (Hi-torque Steelcore® 
Peripheral Guide Wire Abbott Vascular or equivalent). 
5. 7F Swan-Ganz catheter with 0.035in guidewire lumen (Arrow® or 
equivalent) or an angled pigtail catheter.  
6. 3-way stopcock(s) – with Luer-lock connectors (2 for unilateral / 4 for 
bilateral procedures).  
7. Infusion pump(s) and IV tubing for r-tPA infusion(s). 
8. Heparinized saline for flushing. 
9. 0.9% NaCl intravenous (IV) infusion bag 500cc for r-tPA pulse spray 
mixture. 
10. Sterile water for injection, USP (Do not use bacteriostatic water, USP for 
injection) – for 2.2mg vial Cathflo™ Alteplase (r-tPA) mixture (Genentech, 
Inc., South San Francisco, CA). 
11. r-tPA vial(s) for pulse sprays. 
a. Unilateral PE: One (1) 2.2mg vial of Cathflo™ Alteplase (r-tPA) for 
pulse spray use. 
b. Bilateral PE: Two (2) 2.2mg vials of Cathflo™ Alteplase (r-tPA) for 
pulse spray use. 
12. 10cc syringes to administer pulse spray r-tPA 
a. Unilateral PE: Two (2) 10cc syringes for injecting the pulse sprays. 
b. Bilateral PE: Four (4) 10cc syringes for injecting the pulse sprays 
13. Heparinized saline at 500 units/500cc .9% NaCl or 100 units/500cc .9% 
NaCl or .45% NaCl or other standard of care heparinized saline 
concentration, or normal saline without heparin intravenous (IV) pressure 
infusion bag(s) with transducer tubing if the BEC will be used to monitor 
PA pressures in the ICU. 


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14. r-tPA Infusion: 
a. Unilateral PE: Obtain three (3) 2.2mg vials of Cathflo™ Alteplase (r-
tPA) for continuous infusion to be started in the IR suite / cath lab for 
a total of 5mg for one infusion.  Mixture requirements are in section 
8.3. 
b. Bilateral PE: Obtain five (5) 2.2mg vials of Cathflo™ Alteplase (r-tPA) 
for continuous infusion to be started in the IR suite / cath lab for a total 
of 5mg for each infusion for two infusions.  Mixture requirements are 
in section 8.3. 
8.1.2 
Procedure Supplies Provided by the Sponsor 
1. Bashir™ and Bashir™ S-B Endovascular Catheters 
8.2 Baseline Hemodynamic Readings 
The following readings will take place using the Swan-Ganz or angled pigtail catheter in the 
IR suite / cath lab prior to placement of the Bashir™ Endovascular Catheter(s). 
1. PA Pressures measured using a Swan-Ganz catheter or angled pigtail:  PAS / PAD 
/ PA Mean 
2. SpO2 – Pulse Oximeter Arterial Oxygen Saturation 
3. SvO2 – Mixed Venous Oxygen Saturations (from tip of a pigtail catheter or Swan-
Ganz Catheter PA port) 
4. CO – Modified Fick Calculation   
5. CI – Calculation 
8.3 r-tPA Administration - Prepare Pulse Spray(s) and Infusion(s) prior to opening the 
Bashir Endovascular Catheter (BEC). 
8.3.1 
Reconstitution of r-tPA Pulse Spray Mixture  
1. Obtain a 2.2mg vial of r-tPA (1mg/ml) provided by the site. 
2. Mix the lyophilized powdered r-tPA with 2.2ml sterile water for injection 
(as stated in the r-tPA information sheet) to obtain 1mg/ml. Do not use 
bacteriostatic sterile water for injection. 
3. Aspirate exactly 1mg (1ml) into a 3cc syringe (for accuracy).  
4. Inject 1.0mg (1ml) of r-tPA mixture into a 10cc syringe, and aspirate 0.9% 
NaCl to have a maximum of 10cc of diluent and drug mixture in the syringe.   
5. Repeat step 1 through 4 above x 1. 
6. This equals two (2) 10cc pulse spray doses (1.0mg/10cc in one 10cc 
syringes per pulse spray) with 1.0mg r-tPA per dose - Total of 2.0mg of r-
tPA for unilateral PE). 
7. If treating bilateral PE, repeat steps 1 through 5 above, for a total of 4.0mg, 
2.0mg per PA.  This equals four (4) 10cc pulse spray doses (1.0mg/10cc in 
one 10cc syringes per pulse spray). 


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Table 2. r-tPA Doses and Mixtures for Pulse Sprays and Infusions through the BEC 
Pulse Sprays 
 
No. of 2.2mg 
Cathflo™ 
r-tPA Vials 
Required 
Diluent: 
 
Sterile Water 
for Injection 
Total Diluent 
Required 
 
0.9% NaCl 
Total Dose 
per Syringe 
Total 
Syringes 
for Pulse 
Sprays 
Total 
Pulse 
Spray 
Dose 
Unilateral 
PE 
1 
2.2ml per vial 
to have 
1mg/ml 
Total of 20cc 
including  
r-tPA  
1.0mg in each 
10cc syringe 
Two 10cc 
syringes  
2.0mg 
Bilateral 
PE 
2 
2.2ml in 1 vial 
for 1mg/ml 
Total of 40cc 
including  
r-tPA  
1.0mg in each 
10cc syringe 
Four 10cc 
syringes 
4.0mg 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.3.2 
Reconstitution of r-tPA IV Infusion Mixture 
a. Unilateral PE 
i. Obtain a 500cc bag of 0.9% NaCl for infusion. 
ii. Aspirate 5cc of 0.9% NaCl from the 500cc IV bag to have a total 
diluent of 495cc. 
iii. Mix three (3) vials (2.2ml injected into 2.2mg vials) of r-tPA with 
sterile water for injection until the lyophilized powder is dissolved, for 
a total of 6.6mg of r-tPA.  (Do NOT use bacteriostatic water for 
injection). 
iv. Aspirate 5ml (5mg) into a syringe from vials. 
v. Verify 5ml are aspirated into the syringe. 
vi. Inject the 5mg solution of r-tPA into the IV bag for infusion.  The IV 
bag has a total of 5mg of r-tPA in 500cc of diluent. 
b. Bilateral PE 
i. Obtain two (2) 500cc bags of 0.9% NaCl for infusion. 
ii. Aspirate 5cc of 0.9% NaCl from each 500cc IV bag to have a total 
diluent of 495cc in each bag. 
Infusion(s) 
 
No. of 2.2mg 
Cathflo™  
r-tPA Vials 
Required 
Total Diluent  
Required  
 
0.9% NaCl 
Infusion Rate 
Total 
Infusion 
Dose 
Unilateral 
PE 
3 
500cc total including r-tPA 
mixture x 1 bag 
100cc/hr = 1.0mg/hr 
x 1 infusion until 
complete  
5.0mg 
Bilateral 
PE 
 
5 
 
500cc total including r-tPA 
mixture x 2 bags 
100cc/hr = 1.0mg/hr per 
infusion x 2 infusions (1 
into each BEC) until 
complete 
10.0mg 


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iii. Mix five (5) vials (2.2ml injected into 2.2mg vials) of r-tPA with 
sterile water for injection until the lyophilized powder is dissolved, for 
a total of 10mg of r-tPA (1mg/ml).   
iv. Aspirate 5ml (5mg) dose into a syringe from vials. 
v. Verify 5ml are aspirated into the syringe.   
vi. Inject the 5mg solution of r-tPA into one IV bag for infusion.  The IV 
bag has a total of 5mg of r-tPA in 500cc of diluent.  
vii. Repeat steps iv through vi for second IV bag.   
 
9.0 BASHIR™ ENDOVASCULAR CATHETER INVESTIGATIONAL PROCEDURE 
Please refer to the Instructions for Use for complete instructions on preparation, use, and handling 
of the Bashir™ and the Bashir™ S-B Endovascular Catheters (BECs).   
9.1 Baseline Readings - Summary of Procedure Steps  
1. It is recommended that the patient’s blood pressure is under control prior to the 
investigational procedure. 
2. Obtain venous access using ultrasound guidance and micropuncture needle. 
Ultrasound guidance and use of micropuncture needle is mandatory for both CFV 
and IJ access. 
3. Place 7F sheath(s) in the RCFV or access point of choice (CFV or IJ).  CFV or IJ 
access is operator’s choice. 
9.2 Choose one of the two anticoagulation options below according to the investigator’s 
standard of care:  
1. If heparin was administered pre-procedure or patient received LMWH >12 hours 
prior to the BEC procedure, start BEC procedure in the IR suite / cath lab while on 
heparin. Once r-tPA infusion is started, decrease dose of heparin to five (5) to eight 
(8) units/kg/hr up to a maximum of 1,000 units/hr.  
2. If LMWH was administered ≤ 12 pre-procedure, start BEC procedure without 
heparin in the IR suite / cath lab, until patient is eight (8) hours post last dose of 
LMWH. Then start dose of UFH at five (5) to eight (8) units/kg/hr up to a maximum 
of 1,000 units/hr.  ACTs may be checked if standard of care.   
9.3 Summary of Procedure Steps 
1. Using a .035in exchange length wire, insert the wire into a sheath and advance it up 
to the right atrium. 
2. Insert the Swan-Ganz or angled pigtail catheter over the wire and advance it up to 
the right atrium. 
3. Remove the guidewire. 
4. Float the Swan-Ganz catheter or angled pigtail into the pulmonary artery and record 
baseline hemodynamic data  


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5. Insert the exchange length guidewire, or equivalent, into the Swan-Ganz or angled 
pigtail catheter.  Remove the Swan-Ganz or angled pigtail catheter. 
6. Exchange the Swan-Ganz Catheter, or angled pigtail, for a long 7F or greater sheath 
(CFV access) or 7F sheath (IJ access) which is placed into the PA where the 
thrombus is located. 
7. Remove the guidewire and the dilator carefully from the PA making sure that the 
sheath does not jump forward. 
9.3.1 
Intra-procedure Data Collection Requirements 
1. 
Hemodynamic readings 
2. 
AEs / SAEs 
3. 
Times of pulse sprays administration 
4. 
Time the r-tPA infusion(s) started 
5. 
Time of heparin infusion(s) started 
6. 
Technical complications 
7. 
Medications (antiplatelet, anticoagulant, cardiac medications, and 
NSAIDs only) 
8. 
Equipment used 
9. 
Blood pressure and heart rate, at start of procedure 
9.4 Bashir Endovascular Catheter Use – Procedure Steps 
1. Prepare all r-tPA solutions and IV infusion mixtures in Section 8.3 prior to 
opening the Bashir™ Endovascular Catheter (BECs).  The Bashir™ S-B 
Endovascular Catheter may be preferred for smaller patients or for treatment of 
thrombus in the left pulmonary.   
2. Prepare the relevant BEC(s) for use: 
a. Ensure that the infusion basket of the BEC can be expanded and collapsed by 
moving the actuator on the handle backward and forward while depressing the 
white button.  
b. With the basket expanded, flush the basket infusion port with standard flush 
solution. Observe for flush solution exiting the infusion holes of the basket.  
Collapse the basket. 
c. Flush the wire lumen of the BEC observing that flush solution exits the tip of 
the catheter.   
3. Using a .018in x 300cm length steel core non-hydrophilic guidewire, introduce the 
wire into the central lumen of the long sheath. 
4. Backload the BEC onto the 0.018in guidewire and advance towards the long sheath. 
DO NOT insert the BEC into the sheath.   
5. Attach a three-way stopcock to the infusion basket port of the BEC. 
6. Commence r-tPA infusion via the stopcock on the basket infusion line connector 
using an infusion pump. Start the infusion through the BEC PRIOR TO inserting 
the catheter into the sheath. This is to maintain patency during catheter insertion, 
advancement, and positioning in the patient.  


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7. Advance the BEC into the target PA and retract the sheath to expose the basket 
segment.    
8. Do NOT aspirate back from the basket infusion line connector to back bleed.  Only 
maintain forward flow by infusing the r-tPA at the prescribed rate 100cc/hr for 
unilateral PE and bilateral PE, as stated in Table 2.  
9. Keeping the wire in the central wire lumen expand the infusion basket of the BEC. 
9.5 Pulse Spray of r-tPA for Unilateral and Bilateral PE 
a. Unilateral PE:  With the catheter in the target PA, and after verifying that the basket 
portion of the catheter has exited the sheath under fluoroscopy, and with the 
guidewire in place, expand the basket of the catheter to the desired diameter making 
sure that the infusion limbs are expanded to less than the diameter of the vessel wall. 
b. Turn stopcock off to the infusion and administer 10ml (1.0mg r-tPA in 10ml) of 
pulse spray, from the 1st syringe of two syringes, into the thrombus at a steady rate 
over 10-15 seconds.  
c. Under fluoroscopy, with the guidewire in place, collapse the basket and re-expand 
the basket. 
d. Repeat this with the second 10cc syringe (1.0mg r-tPA in 10ml) over 10-15 seconds. 
e. As soon as the pulse sprays are administered, turn the stopcock open to the r-tPA 
infusion to restart the r-tPA via the infusion port of the BEC. 
Please note: Even if the clot appears to be primarily unilateral, the default should be 
to use a second BEC in the contralateral pulmonary artery if there is any substantial 
clot on the contralateral side.   
f. Bilateral PE: Repeat, using a second BEC, steps a-e for bilateral PE. 
g. Once pulse sprays are complete, the basket(s) should remain expanded. 
h. Remove the guidewire(s), attach a 3-way stopcock and connect fluid or cap off the 
line. (See specifics at 9.9.3).  
Please note that the BEC is to be placed in the optimal location to treat the PE.  It is 
NOT to be used to selectively cannulate multiple branches of the pulmonary 
vasculature in multiple locations to administer the r-tPA.  
9.6 r-tPA Infusion – Prior to Departing the IR Suite / Cath Lab 
1. For unilateral PE: The total r-tPA infusion is 5mg at 1.0mg/hr. Using an IV pump 
at 100cc/hr, infuse the 500cc of 0.9% NaCl with the 5mg r-tPA at 1.0mg/hr until 
infusion is complete (approximately 5 hours). 
2. For bilateral PE: The r-tPA infusion is 5mg at 1.0mg/hr into each BEC. Using two 
(2) IV pumps at 100cc/hr, infuse the 500cc of 0.9% NaCl x 2 simultaneously for 
1.0mg/hr into each PE until complete (approximately 5 hours), for a total infusion 
dose of 10mg.  


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9.7 Anticoagulation Post-BEC Procedure 
Heparin infusion at the completion of the BEC procedure and during the r-tPA infusion 
1. Continue heparin administration through the side arm of the sheath at five (5) to 
eight (8) units/kg/hr up to a maximum of 1,000 units/hr.  If bilateral BECs are in 
place, the heparin infusions must be administered into each sheath.  Administer half 
(or approximately half) the dose prescribed by the investigator into the side arm of 
each sheath to equal the prescribed dose. 
2. If subject has not reached 8hrs post last does of LMWH in the IR suite / cath lab, 
then in the ICU start dose of UFH to five (5) to eight (8) units/kg/hr up to a 
maximum of 1,000 units/hr. 
9.8 Maintaining Patency Through the Central Lumen of the BEC(s) During Transport 
to ICU 
To maintain patency of the central lumen (guidewire lumen) of the BEC(s) during 
transport to the ICU, follow hospital standard protocol during transport to ICU, unless 
the BEC central lumen is not going to be used for PA pressure monitoring in the ICU 
and it is capped off. 
9.9 Preparation in IR Suite / Cath Lab for Transfer to ICU 
1. Suture sheaths in place. 
2. Secure r-tPA and heparin drips to maintain infusions in the ICU. 
3. The BEC central lumen (guidewire lumen) may be used to monitor PA pressures in 
the ICU. 
a. Option #1: Connect fluid to central lumen (guidewire lumen) at hospital 
standard of care dose and rate (e.g. heparinized saline at 500 units/500cc .9% 
NaCl or 100 units/500cc .9% NaCl or .45% NaCl or other standard of care 
saline concentration, or normal saline without heparin) using pressure tubing to 
the stopcock  to maintain patency until removal of the BEC(s).  Using this set-
up provides the option of monitoring the PA pressures in the ICU during the r-
tPA infusion.   
b. Option #2:    If the central lumen of the BEC(s) is/are not going to be used for 
monitoring pressure in the ICU, the central lumen may be capped off prior to 
leaving the IR Suite / Cath Lab. 
4. Securing the device(s):   
a. For CFV Access: tape device to thigh.  Then follow step “5” below. 
b. For Right IJ Access: Cover the catheter with a sterile sleeve (such as the sleeve 
that comes with a Swan-Ganz catheter) tape device to left pectoral area with the 
shaft of the catheter placed posterior to the neck.  Then follow step “5” below. 
Do the opposite for Left IJ access. 
5. Place a strong adhesive dressing, such as Tegaderm™ (3M™, St Paul, MN) or 
equivalent tape over the handle and the actuator (slider) to make sure the handle and 
actuator (slider) are secure and cannot be moved. 


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6. For femoral access, a knee brace is recommended to prevent the patient from 
bending his/her knee when the BEC is in place. 
10.0 
POST-PROCEDURE PATIENT MANAGEMENT AND TESTS 
The study subject will be admitted to the intensive care unit (ICU) where nursing staff are 
experienced in the care of patients treated for pulmonary embolisms. 
10.1 
r-tPA Infusion – Intensive Care Unit 
1. r-tPA Infusion: Maintain the r-tPA Infusion through the infusion line on the side 
of the handle of the BEC in the ICU for approximately five (5) hours from start of 
the infusion in the IR suite / cath lab.  The infusion should run at the rate prescribed 
in this protocol until the infusion is complete. See section 8.3 
10.2 
Post-r-tPA Infusion: 
1. Maintain BEC Infusion Basket Patency: Once the r-tPA infusion is complete, 
maintain patency through the infusion basket of the BEC(s) by replacing r-tPA 
infusion with heparinized saline (per hospital standard of care e.g. 500 units/500cc 
.9% NaCl or  100 units/500cc .9% NaCl or other standard of care heparinized 
concentration) using an infusion pump, at 30cc/hr, until the BEC(s) is / are 
removed.  Please note this solution must be heparinized. 
2. Anticoagulation Post-r-tPA infusion: At the completion of r-tPA infusion, 
increase heparin dose to therapeutic doses with target aPTT in therapeutic range 
(suggested 60-80sec). 
3. Physical Exam: A physical exam is required to be performed as soon as possible 
after the completion of the r-tPA infusion.  
10.3 
The Completion of r-tPA Infusion in the ICU  
1. The BEC catheter(s) will be removed as soon as possible at the end of infusion only 
by an operator trained and approved to place and remove the study device. Collapse 
the basket(s) of the BEC(s).  
2. Remove the BEC by retracting the catheter(s) carefully into the sheath(s) and then 
removing them from the body. Do not remove the sheath(s) at this time. 
3. Please note: If pressurized tubing set-up was used to monitor the pressure through 
the central lumen of a BEC in the ICU, aseptically remove the tubing from the port 
at the back of the BEC and set aside for using for step 5a below.   
4. Back bleed the sheath(s) and flush with heparinized saline. 
5. Attach pressure tubing to the side arm of the sheath(s) and record the following: 
a. Final hemodynamic parameters (PAS, PAD, PA Mean) – record from each PA 
if bilateral PE with bilateral sheaths in place. 
b. SpO2 – Pulse oximetry oxygen saturation.  
c. SvO2 – Mixed venous oxygen saturation. 
d. CO – Calculate using the Modified Fick formula. 


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e. CI – Calculate using the Modified Fick formula. 
6. After BEC removal, the long sheath may be exchanged for a short sheath once the 
hemodynamic parameters have been recorded if the sheaths are not removed at the 
completion of the r-tPA infusion (after the effects of the r-tPA have worn off).  
10.4 
Sheath Removal 
1. Sheath removal: Stop UFH for at least one (1) hour prior to sheath removal, unless 
the operator believes that the UFH, in the best interest of the patient, should not be 
stopped prior to and during sheath removal.  Remove sheaths according to standard 
of care. 
2. Anticoagulation Post-Sheath Removal: Re-start anticoagulation within one (1) 
hour post sheath removal with LMWH 1mg/kg SQ q12hrs or UFH at therapeutic 
doses for 24 hours post sheath removal. After 24 hours post sheath removal, 
physicians can start therapeutic anticoagulation according to their standard of care. 
If physicians choose to use DOACs then patients should be properly loaded 
according to the current guidelines.   
11.0 
TESTS REQUIRED 24 HOURS AFTER COMPLETION OF THE R-TPA 
INFUSION  
11.1 
Laboratory Tests and Other Tests 
1. BMP, CBC, Cardiac Biomarkers Troponin and BNP – These tests will be drawn 
24 hours (±8 hours) after completion of the r-tPA infusion. 
11.2 
Assessments 
1. Physical Examination – The physician will perform a physical examination at the 
end of the infusion and 24 hours after completion of r-tPA infusion. 
2. AE/SAEs – Adverse events will be monitored and reported on the CRF post-
procedure through 24 hours. 
11.3 
Data Collection 
The following data will be collected and documented in the CRF in addition to the 
required pre-procedure testing. 
1. Medications – All antiplatelet, anticoagulant, cardiac medications, and NSAIDs 
will be recorded that are administered within 24 hours following the infusion.  
2. Laboratory Test Results – Tests performed above will be documented in the 
CRF. 


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12.0 
TESTS REQUIRED 48 HOURS AFTER COMPLETION OF THE R-TPA 
 
INFUSION  
12.1 
Imaging 
1. CTA – A CTA will be performed at 48 hours (±8 hours) after the completion of 
the r-tPA infusion. 
12.2 
Assessments 
1. AE/SAEs – Adverse events will be monitored and reported on the CRF post-
procedure through discharge. 
12.3 
Data Collection 
1. Medications – All antiplatelet, anticoagulant, cardiac medications, and NSAIDs 
will be recorded that are administered within 48 hours following the infusion.  
2. RV/LV Diameter Ratio – This will be measured and calculated by CTA at 48 
hours (±8 hours) following completion of the r-tPA infusion. 
13.0 
ASSESSMENTS REQUIRED 72 HOURS FOLLOWING START OF  R-TPA 
 
INFUSION 
13.1 
Assessments 
1. AE/SAEs – Adverse events will be monitored and reported on the CRF post-
procedure through discharge.  
 
Please note the primary safety endpoint assessment for bleeding within 72 hours 
will be assessed through 72 hours (-4 / +12 Hours) following initial administration 
of the r-tPA infusion in the IR suite / cath lab.   
13.2 
Data Collection 
1. Medications – All antiplatelet, anticoagulant, cardiac medications, and NSAIDs 
will be recorded that are administered within 72 hours following the infusion.  
2. If Subject has been discharged Prior to 72 Hour Visit – If the study subject is 
discharged from the hospital prior to the 72-hour visit, the assessment may be 
conducted over the phone.  
3. COVID-19 Impact - A COVID-19 Site Impact Assessment Form will be 
completed and submitted to the CRO prior to visits to be impacted by COVID-19.  


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14.0 
ASSESSMENTS REQUIRED JUST PRIOR TO HOSPITAL DISCHARGE 
14.1 
Assessments 
1. Physical Examination – The physician will perform a physical examination 
within eight (8) hours prior to discharge.   
2. AE/SAEs – Adverse events will be monitored and reported on the CRF post-
procedure through discharge. 
15.0 
30-DAY FOLLOW-UP VISIT POST PROCEDURE 
15.1 
Assessments 
1. Physical Examination – The physician will perform a physical exam at 30-day 
follow-up visit (±7 days).  
2. AEs/ SAEs – All adverse events will be recorded at the 30-day follow-up visit.    
3. COVID-19 Impact – If, as referenced in section 6.4.4 of this protocol, the subject 
is unable to attend the 30-Day Follow-Up Visit in person due to COVID-19, the 
assessment may be done over the phone or by video conference. Documentation 
of the visit and how it was impacted by COVID-19 must be documented on the 
CRF. Any visit-related procedure that is not completed for the 30-Day Follow-up 
Visit under this COVID-19 amendment will be reported as a deviation. Data 
Collection 
1. Medications – All antiplatelet, anticoagulant, cardiac medications, and NSAIDs 
post-discharge will be recorded at this visit. 
16.0 
ANTICIPATED ADVERSE EVENTS  
The following events are anticipated adverse events in subjects who are treated for pulmonary 
embolism. An adverse event is any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) in subjects, users or other 
persons, whether or not related to the investigational medical device.   
The signs, symptoms, and sequelae of an underlying adverse event (linked 
pathophysiologically to the AE) should not be reported as separate adverse events.  All adverse 
events, of any type, are to be recorded on an Adverse Event case report form. 
Table 3 lists the anticipated adverse events identified for the Bashir™ and the Bashir™ S-B 
Endovascular Catheters (BECs). 
Table 4 lists the anticipated adverse events identified for the r-tPA infusion. 
Table 5 lists the anticipated adverse events identified for the pulmonary embolism procedure. 
 


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Table 3. Anticipated Adverse Events Related to the Investigational Device22 
Adverse Event 
Definition 
Allergic 
reactions 
Any exaggerated immune response to a foreign antigen regardless of 
mechanism 
Hematoma at 
access site 
Blood collects under the skin in the area where the physician accessed 
the femoral artery to perform the treatment, and results in bruising 
(ecchymosis) 
Hemorrhage  
A profuse discharge of blood from a ruptured blood vessel resulting in 
a decrease in hemoglobin 
Intimal damage   Trauma to the intimal lining of the vessel 
Ischemia  
Inadequate blood supply to an organ or part of the body or heart muscles 
Pain and 
tenderness  
Discomfort in an area that is impacted by the device 
Vascular 
thrombosis  
A formation of a blood clot in an artery or vein 
Vessel 
perforation  
A hole or tear in an artery or vein 
Vessel spasm 
A temporary tightening (constriction) of the muscles in the wall of one 
of the arteries that supplies blood flow 
 
Table 4.  Anticipated Adverse Events Related to r-tPA Infusion15,19 
Adverse Event 
Definition 
Fever 
Elevated temperature above normal 
Hematuria 
Blood in the urine  
Hematoma 
Collection of blood under the skin 
Hemoptysis 
Coughing up blood  
Hypotension 
Sustained low blood pressure, below normal (Usually indicative of
MAP< 60 mmHg) 
Mucosal bleeding 
Bleeding in the mouth 
Pleural effusion 
Fluid accumulation around the lung 
Pulmonary edema 
Fluid accumulation in the tissue and air spaces of the lungs 
Pulmonary  
re-embolization 
Sudden blockage of a major pulmonary artery   
Thromboembolism Obstruction of a blood vessel by a clot that has become dislodged 
  
 
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Table 5. Anticipated Adverse Events Related to the Procedure23 
Adverse Event 
Definition 
Access site 
pseudoaneurysm 
Sometimes called a false aneurysm, occurs when a blood vessel wall 
is injured, and the blood is contained by the surrounding tissues 
Anemia 
Deficiency of red blood cells  
Arrhythmia 
Abnormal heart rhythm 
Bleeding requiring 
blood transfusion 
Any loss of blood that may or may not require medical intervention 
Cardiac arrest 
Permanent or temporary cessation of organized heart function 
requiring emergency CPR, cardioversion, or defibrillation 
Death 
The permanent end of vital processes in a cell or tissue 
Ecchymosis 
Bruising  
Hematuria 
Blood in the urine 
Hemodynamic 
instability 
Blood pressure requires vasopressor support. 
Heparin induced 
thrombocytopenia 
Caused by antibodies that bind to complexes of heparin and platelet 
factor 4 (PF4), activating the platelets and promoting a 
prothrombotic state 
Infection 
Bacteria in the blood or at the access site 
Pain at access site 
Discomfort at site of catheter insertion 
Perforation 
A hole or tear in a vessel 
Pneumothorax 
A presence of air or gas in the cavity between the lungs and the chest 
wall, causing collapse of the lung 
Pulmonary infarct 
Death of a portion of lung tissue caused by an interruption of blood 
supply 
Shock 
A life-threatening medical condition of low blood perfusion  
Skin necrosis (if 
on warfarin) 
A condition in which skin and subcutaneous tissues die due to long 
term treatment with warfarin 
17.0 
ADVERSE EVENT REPORTING 
17.1 
Serious Adverse Events   
An adverse event is any undesirable experience associated with the use of a medical 
product in a patient. The event is serious and will be collected when the patient outcome 
is: 
1. Death 
2. Life-threatening - Report if suspected that the patient was at substantial risk of dying 
at the time of the adverse event or use or continued use of the device or other 
medical product might have resulted in the death of the patient. 
3. Hospitalization (initial or prolonged) - Report if admission to the hospital or 
prolongation of hospitalization was a result of the adverse event. 
Emergency room visits that do not result in admission to the hospital should be 
evaluated for one of the other serious outcomes (e.g., life-threatening; required 
intervention to prevent permanent impairment or damage; other serious medically 
important event). 


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4. Disability or Permanent Damage - Report if the adverse event resulted in a 
substantial disruption of a person's ability to conduct normal life functions, i.e., the 
adverse event resulted in a significant, persistent or permanent change, impairment, 
damage or disruption in the patient's body function/structure, physical activities 
and/or quality of life. 
5. Congenital Anomaly/Birth Defect - Report if you suspect that exposure to a medical 
product prior to conception or during pregnancy may have resulted in an adverse 
outcome in the child. 
6. Required Intervention to Prevent Permanent Impairment or Damage (Devices) - 
Report if you believe that medical or surgical intervention was necessary to 
preclude permanent impairment of a body function, or prevent permanent damage 
to a body structure, either situation suspected to be due to the use of a medical 
product. 
7. Other Serious (Important Medical Events) - Report when the event does not fit the 
other outcomes, but the event may jeopardize the patient and may require medical 
or surgical intervention (treatment) to prevent one of the other outcomes. Examples 
include allergic bronchospasm (a serious problem with breathing) requiring 
treatment in an emergency room, serious blood dyscrasias (blood disorders) or 
seizures/convulsions that do not result in hospitalization. The development of drug 
dependence or drug abuse would also be examples of important medical events. 
17.2 
Unanticipated Adverse Device Effect  
Unanticipated adverse device effect is any serious adverse effect on health or safety, 
any life-threatening problem or death caused by, or associated with a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the application; or any other unanticipated serious problem associated 
with a device that relates to the rights, safety, or welfare of subjects.  
17.3 
Adverse Event Documentation 
All adverse events (AEs) including those categorized as anticipated, life threatening, 
serious, unexpected, and suspected are to be reported on the case report form. 
 
 
 
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17.4 
Adverse Event Relatedness 
Table 6. Adverse Event Categories of Study Device or Drug Relatedness 
Relatedness 
Term 
Relatedness Definition 
Related 
There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an 
abnormal laboratory test result, occurs in a plausible time relationship to 
drug administration or use of device and cannot be explained by 
concurrent disease or other drugs or chemicals. The event must be 
pharmacologically or phenomenologically definitive. 
Probably 
Related 
There is evidence to suggest a causal relationship, and the influence of 
other factors is unlikely. The clinical event, including an abnormal 
laboratory test result, occurs within a reasonable time after administration 
of the drug or use of device, is unlikely to be attributed to concurrent 
disease or other drugs or chemicals. 
Possibly 
Related 
There is some evidence to suggest a causal relationship (eg, the event 
occurred within a reasonable time after administration of the trial 
medication or use of device). However, other factors may have contributed 
to the event (eg, the participant’s clinical condition, other concomitant 
events). Although an AE may rate only as “possibly related” soon after 
discovery, it can be flagged as requiring more information and later be 
upgraded to “probably related” or “definitely related”, as appropriate. 
Not Related 
The adverse event is completely independent of study drug administration 
or use of device, and/or evidence exists that the event is definitely related 
to another etiology. 
 
 
 
 
 
 
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Table 7. Adverse Event Categories of Procedure Relatedness 
Relatedness 
Term 
Relatedness Definition 
Related 
There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an 
abnormal laboratory test result, occurs in a plausible time relationship to 
the interventional procedure. 
Probably 
Related 
There is evidence to suggest a causal relationship, and the influence of 
other factors is unlikely. The clinical event, including an abnormal 
laboratory test result, occurs within a reasonable time after the 
interventional procedure. 
Possibly 
Related 
There is some evidence to suggest a causal relationship (e.g, the event 
occurred within a reasonable time after interventional procedure). 
However, other factors may have contributed to the event (e.g, the 
participant’s clinical condition, other concomitant events). 
Not Related 
The event is completely independent of the interventional procedure, 
and/or evidence exists that the event is definitely related to another 
etiology. 
17.5 
Investigator SAE Reporting Requirements 
An SAE occurring during the study or within 30 days of stopping the treatment must 
be reported to the study safety monitor. Any such SAE due to any cause, whether or 
not related to the study medication, must be reported within 24 hours of occurrence or 
when the investigator becomes aware of the event.  
The investigator must send a preliminary report of any such SAE to the project 
manager via the EDC system within 24 hours or if this is not possible via email or fax 
using an SAE Report Form, or at a minimum by telephone.   
The event must be recorded on the electronic SAE CRF page. Preliminary reports of 
SAEs must be followed by detailed descriptions, including clear pseudonymized 
photocopies of hospital case reports, consultant reports, autopsy reports, and other 
documents when requested and applicable. All photocopies should be redacted to 
remove study subjects’ personal details and annotated with the patient’s unique study 
identifiers. SAE reports must be made whether or not the investigator considers the 
event to be related to the investigational drug.  Appropriate remedial measures should 
be taken to treat the SAE, and the response to treatment should be recorded. Study 
subjects must be closely followed until sufficient information is obtained to indicate a 
return to normal status or until the event stabilizes at a level acceptable to the 
investigator.  
18.0 
REGULATORY REQUIREMENTS 
The following are requirements of the sponsor and of the investigators.  


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18.1 
Investigator Responsibilities 
The following responsibilities are required for investigators participating in this 
study: 
 
An investigator is responsible for ensuring that the investigation is conducted 
according to the signed agreement, the protocol, and applicable FDA regulations, 
for protecting the rights, safety and welfare of subjects under the investigator’s 
care and for the control of devices under investigation. An investigator also is 
responsible for ensuring that informed consent is obtained in accordance with 21 
CFR part 50. Specific responsibilities include: 
 
1. An investigator is responsible for ensuring that an investigation is conducted 
according to the signed agreement, the protocol and applicable FDA 
regulations, for protecting the rights, safety, and welfare of subjects under the 
investigator's care, and for the control of devices under investigation. An 
investigator also is responsible for ensuring that informed consent is obtained 
in accordance with part 50 of this chapter. Additional responsibilities of 
investigators are described in 21 CFR 812 subpart E. 
2. Awaiting approval: an investigator may determine whether potential subjects 
would be interested in participating in an investigation but shall not request 
the written informed consent of any subject to participate and shall not allow 
any subject to participate before obtaining FDA and IRB approval. 
3. Compliance: an investigator shall conduct an investigation in accordance 
with the signed agreement with the sponsor, the investigational plan, any 
applicable FDA regulations and any conditions of approval impose by an IRB 
or FDA. 
4. Supervising Device and Drug Use: an investigator shall permit an 
investigational device and drug to be used only with subjects under the 
investigator’s supervision and shall not supply an investigational device to 
any person not authorized under FDA regulation to receive it.  
5. Financial Disclosure: an investigator shall disclose to the sponsor sufficient 
accurate financial information to allow the applicant to comply with 21 CFR 
54 and shall promptly update this information if any relevant changes occur 
during the course of the investigation and for 1 year following completion of 
the study. 
6. For FDA approved and IRB approved protocols, a PI Agreement is required 
to be reviewed and signed by the principal investigator prior to 
commencement of enrollment.  PI Agreements are required to be signed after 
FDA and IRB approval of subsequent protocol amendments.  
7. A Sub-I Agreement is required to be completed and signed by the sub-
investigator prior to the Sub-I’s commencement of enrollment. 
8. Disposing of Device and Drug: upon completion or termination of the 
investigator’s part of an investigation, return to the sponsor any remaining 
supply of the device or otherwise dispose of the device as the sponsor directs. 


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9. Investigator Records and Reports: participating investigator shall maintain 
the following accurate, complete, and current records relating to the 
investigator's participation in an investigation: 
a. All correspondence with another investigator, an IRB, the sponsor, a 
monitor, or FDA, including required reports. 
b. Records of receipt, use or disposition of a device that relate to: 
i. The type and quantity of the device, the dates of its receipt, and the 
batch number or code mark. 
ii. The names of all persons who received, used, or disposed of each 
device. 
iii. Why and how many units of the device have been returned to the 
sponsor, repaired, or otherwise disposed of. 
10. Records of each subject's case history and exposure to the device. Case 
histories include the case report forms and supporting data including; for 
example, signed and dated consent forms and medical records including, for 
example, progress notes of the physician, the individual's hospital chart(s), 
and the nurses' notes. Such records shall include: 
a. Documents showing evidence of informed consent and, for any use of a 
device by the investigator without informed consent, any written 
concurrence of a licensed physician and a brief description of the 
circumstances justifying the failure to obtain informed consent. The case 
history for each individual shall document that informed consent was 
obtained prior to participation in the study. 
b. All relevant observations, including records concerning adverse device 
effects (whether anticipated or unanticipated), information and data on the 
condition of each subject upon entering, and during the course of, the 
investigation, including information about relevant previous medical 
history and the results of all diagnostic tests. 
c. A record of the exposure of each subject to the investigational device, 
including the date and time of each use, and any other therapy. 
11. The protocol, with documents showing the dates of and reasons for each deviation 
from the protocol. 
12. Any other records that FDA requires to be maintained by regulation or by specific 
requirement for a category of investigations or a particular investigation. 
13. The Principal Investigator is required to prepare and submit to the Sponsor the 
following complete, accurate, and timely reports on this investigation, when 
necessary:  
a. Withdrawal of IRB approval (within 5 working days) 
b. Progress report, if applicable (annually)  
c. Deviations from the protocol (Not permitted unless to protect the health, 
safety, welfare of the patient) 
d. Informed consent deviations (within 5 working days) 
e. Final report 


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14. Core Lab Data Acquisition:  Provide core labs with recorded media according to 
the core lab protocols within the specified timeframe in the core lab instruction 
manual. Independent core lab for CTA: 
Syntactx, LLC 
Richard Ouriel  
SVP, Clinical Services  
4 World Trade Center 
150 Greenwich Street, Floor 44 
New York, NY 10007  
Phone: 212-878-6885 
Email: rouriel@syntactx.com 
 
Publication:  The Principal Investigator shall not create any publication related to 
this study without the express written permission of the sponsor.  Should the 
principal investigator wish to publish or present the results of single-center results 
from this study, the principal investigator agrees to collaborate with the principal 
investigators participating in this study and provide the sponsor with an abstract, 
manuscript, and/or presentation for review 60 days prior to submission for 
publication or presentation. Once initial results are published, the site principal 
investigator may publish single-center results in collaboration with the sponsor.  
 
The sponsor retains the right to delete from the manuscript confidential 
information and to object to suggested publication and/or its timing (at the device 
manufacturer’s sole discretion).  
18.2 
Sponsor Responsibilities 
1. General Duties 
a. Submitting the IDE application to FDA. 
b. Obtaining both FDA and IRB approvals for the investigation before shipping 
the devices and drugs to any investigator. 
c. Obtaining FDA approval and IRB approval for a supplemental application 
before beginning that portion of the investigation. 
d. Selecting qualified investigators. 
e. Ensuring proper monitoring.  
f. Ensuring sites adhere to patient informed consent being documented and 
obtained. 
2. Selection of Investigators 
a. Assure selection of investigators qualified by training and experience 
b. Shipping the investigational device only to participating investigators 
c. Obtaining a signed investigator's agreement containing: 
i. Investigator's curriculum vitae 
ii. Statement of investigator's relevant experience, including dates 
iii. Location, extent, and type of experience 


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iv. If an investigator was involved in an investigation or other research that 
was terminated, an explanation of the circumstances that led to the 
termination 
v. Statement of the investigator's commitment to: 
 
Conduct the investigation in accordance with the agreement, the 
investigational plan, 21 CFR Parts 50, 56, and 812, and any conditions 
of approval imposed by the IRB or FDA 
 
Supervise all testing of the device involving human subjects 
 
Ensure that the requirements for informed consent are met (21 CFR 
Part 50) 
3. Providing investigators with the necessary information to conduct the investigation 
including, but not necessarily limited to: 
a. The Protocol 
b. Final Report from Protocol THRO-CLIN-2018-01 
c. IFUs 
d. Case Report Form 
e. Informed Consent 
f. FDA Letter to Commence the Study 
 
4. 
Refer to Section 17 for Safety Reporting Requirements 
18.3 
Record Retention 
Subject study records, correspondence files, all supporting study documentation, and 
reports must remain on file at the investigational site for a minimum of two years or in 
line with the institutional document retention policy (if longer) after the 
completion/termination of this study or when it is no longer needed to support a 
marketing application, whichever is later.  The Principal Investigator must contact 
Thrombolex, Inc. before destroying or archiving off-site any records and reports 
pertaining to this trial to ensure that they no longer need to be retained on site.  
Thrombolex, Inc. reserves the right to have all documents shipped to its office at the 
end of the two-year retention period at its own cost. 
18.4 
Emergency Circumstances 
If emergency circumstances unrelated to the study should occur, Thrombolex, Inc. will 
follow the FDA guidance on how to manage the ongoing investigation during such 
crisis.31 
19.0 
DEVICE AND DRUG ACCOUNTABILITY 
19.1 
Bashir™ Endovascular Catheter Packaging for the IR Suite / Cath Lab 
The Bashir™ Catheters are packaged to provide protection during transportation and 
to facilitate introduction into the sterile environment.  The shaft of the Bashir Catheter 


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is inserted into a protective tube, mounted to a 0.3” wide x 46.5” long; .020” HDPE is 
inserted into a peel-pouch is shipped in a dispenser box. 
19.2 
Device Accountability 
A packing slip will accompany all devices in each shipping box, 1 slip for multiple 
catheters.  The site will retain the packing slips in their regulatory binder.  The site 
should document each device and device disposition on the device accountability log 
provided to the site by the CRO. 
19.3 
Drug Accountability 
The study drug is commercially available and is to be purchased by the institution.  The 
site should document each vial and drug disposition in the case report form for each 
study subject.     
20.0 
STATISTICAL CONSIDERATIONS - ENDPOINTS, HYPOTHESES, AND 
 
ANALYTICAL METHODS 
20.1 
Power and Sample Size Calculation 
The study will enroll up to 125 patients with the goal to have 100 evaluable subjects 
(after accounting for a 20% attrition rate of subjects who are enrolled and treated) in a 
prospective, non-randomized, multi-center study. The following assumptions were used 
to determine the required sample size for the study: 
 
This study would have an attrition rate of subjects enrolled and treated no greater 
than 20%. 
 
A mean reduction of 28% in the primary efficacy endpoint (RV/LV diameter 
ratio) after 48 hours in BEC-treated patients.  It will be compared to the 
performance goal of 20% reduction in RV/LV diameter ratio after 48 hours. 
 
A standard deviation (SD) on the scale of percent change for the primary efficacy 
endpoint (RV/LV ratio) of 25%. 
 
An interim analysis will be conducted once data on 60 participants have been 
collected, in order to obtain preliminary efficacy results using the primary 
efficacy endpoint. To constrain the overall type I error rate, an O’Brien-Fleming 
alpha spending function will be utilized, in which a stringent type I error rate of 
alpha=0.0038 will be used for the interim analysis, leaving alpha=0.0212 for the 
final analysis, when study data are complete. 
Alpha values for interim and final analyses were obtained from the R package ldbounds 
function bounds(), which calculates alpha given the type of spending function, timing 
of the interim analyses, and overall type I error desired.  The parameters used to obtain 
these alpha values were O’Brien-Fleming spending function, single interim analysis at 
60% of total sample, and overall alpha of 0.025 (one-sided). 


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The sample size needed for 80% power to test the primary efficacy hypothesis in the 
final analysis is 83 subjects, based on the assumptions stated above, and alpha = 0.0212.6   
This estimate is based on a one-sided one-sample t-test of mean percent change from 
baseline to 48-hour assessment, comparing the percent change in RV/LV ratio that is 
predicted in this study with a 20% reduction. 
20.2 
Endpoints, Hypotheses, and Analytical Methods 
20.2.1 Primary Efficacy Endpoint:  
The primary efficacy endpoint is reduction in the chest CT-measured RV/LV diameter 
ratio assessed by contrast enhanced chest CT from baseline within 48 ± 6 hours of 
initiation of treatment. 
20.2.2 Hypothesis:  
The predicate device for Bashir Endovascular Catheter is the EkoSonic Endovascular 
System (EKOS, Bothell, WA). The SEATTLE II Study reported a reduction in RV/LV 
diameter ratio of -0.42 ± 0.36 (mean ± SD) in 115 patients who underwent a within-
window CT measurement of RV/LV diameter ratio. We hypothesize that RV/LV 
diameter ratio measured at 48 hours compared with measured ratio at baseline will be 
reduced on average by more than 20%. 
20.2.2.1 Analytical methods:  A change score d will be calculated:  
𝒅ൌ  𝑹𝟒𝟖െ𝑹𝟎
𝑹𝟎
 
that expresses the change as a proportion of the baseline value, where R0 and R48 are  
ୖ୚
୐୚ 
at time 0 and 48 hours post-treatment, respectively.  A larger decrease from baseline 
will result in a change score with a greater magnitude and a negative sign.  The change 
score will be compared to the benchmark value of 20% in a one-sided hypothesis test: 
𝑯𝟎: 𝒅൒െ𝟎. 𝟐 
𝑯𝑨: 𝒅൏െ𝟎. 𝟐 
The distribution of the change score will be examined to assess whether the normality 
assumption is met, using both graphical methods (Q-Q plots and histograms) as well as 
multiple hypothesis tests of normality (Shapiro-Wilk, Kolmogorov-Smirnov, 
Anderson-Darling, and Cramer-von Mises).  Multiple hypothesis testing methods will 
be employed to assess normality because the choice of the most powerful test depends 
on the distributional qualities of the data; if the different tests do not result in the same 
conclusion, more weight will be given to the method that is best suited to the observed 
distributional qualities of the data (e.g., heaviness of tails).  If the data are determined 
to be normal based on these methods, a t test will be done; if not, a one-sample Wilcoxon 


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signed rank test (the non-parametric alternative to the one-sample t test) will be done. 
In addition, the t-test will be presented for the primary endpoint analysis regardless of 
the normality of the test results. 
The test will be performed twice: once at the interim analysis (with α=0.0038) and once 
at the final analysis (with α=0.0212).  If the p-value is less than α at either analysis, then 
the test will be considered statistically significant.  
20.2.3 Primary Safety Endpoint:  
The primary safety endpoint is major bleeding within 72 hours of procedure initiation 
of r-tPA infusion (the start of the infusion). Bleeding events are classified by the 
International Society of Thrombosis and Hemostasis (ISTH). 
20.2.4 Hypothesis:  
The comparator device for Bashir Endovascular Catheter is the EkoSonic Endovascular 
System (EKOS, Bothell, WA), and results from the study evaluating the safety and 
efficacy of this device were the basis for the performance goal of 14.9% proposed for 
this study. The SEATTLE II Study reported a 10% (standard error=2.45%) of moderate 
to severe bleeding in treated subjects within 72 hours of the treatment initiation.  The 
hypothesis is that the bleeding rate in this study will not exceed 10% + 2*SE = 14.9%.  
A one-sided, one-sample exact test of a binomial proportion p will be used to test the 
hypotheses below. 
𝑯𝟎: 𝒑൒𝟎. 𝟏𝟒𝟗 
𝑯𝑨: 𝒑൏𝟎. 𝟏𝟒𝟗 
The hypothesis test for the primary safety endpoint will not be done at the interim 
analysis, but only at the end of the study.  This test will have a type I error rate of 0.025. 
20.2.5 Secondary Endpoints:  
Descriptive statistics will be generated for the secondary endpoints listed below.  For 
continuous measures (e.g., Modified Miller Index comparing 48 hours post therapy to 
baseline), the mean and 95% confidence limits will be calculated, along with the 
median, standard deviation and range.  For frequency outcomes (e.g., device success), 
results will be reported as the overall frequency of occurrence as well as the percentage 
of subjects.    
1. Device Success: The number of devices with therapy delivered without a device 
failure. 
2. Refined Miller Score as measured on contrast enhanced chest CT (CTA) within 48 
hours after the completion of the r-tPA infusion compared to baseline as measured 
by core lab.  
3. All-cause mortality at hospital discharge through 30-day follow-up. 


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4. SAEs through 30-day follow-up. 
5. AEs through 30-day follow-up. 
6. UADEs through 30-day follow-up. 
7. Recurrent PE through 30-day follow-up.  
8. 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:  
a. Requiring medical intervention by a healthcare professional.  
b. Leading to hospitalization or increased level of care.  
c. Prompting a face to face (i.e., not just a telephone or electronic 
communication) evaluation.  
9. Technical procedural complications. 
10. Systolic PA pressure measured at completion of infusion after BEC(s) removal 
and compared to baseline. 
11. Cardiac output (CO by Modified Fick calculation in Protocol) and cardiac index 
(CI) following completion of the r-tPA infusion compared to the baseline. 
20.2.6 Poolability, Subgroup, and Sensitivity Analysis 
To assess poolability by study site, analyses will be done that test whether study site is 
a predictor of the primary efficacy and safety outcomes.  Two regression models will 
be fit: a linear regression model having RV/LV diameter ratio as the dependent variable, 
and a logistic regression model having whether major bleeding occurred (as defined by 
ISTH within 72 hours of initiation of r-tPA infusion) as the dependent variable.  Each 
model will include site as an independent variable and test the hypothesis that study site 
was a significant predictor of each dependent variable.  If the hypothesis tests show that 
site is not a significant predictor of either outcome, it will be concluded that the study 
sites do not differ substantially in terms of outcome, and the data from sites will be 
pooled for analysis of all primary and secondary endpoints.   
For the primary endpoints, descriptive statistics by site will be listed: the mean ± 
standard deviation, minimum, and maximum RV/LV diameter ratio, and the proportion 
of patients experiencing major bleeding, will be calculated for each study site and 
presented in a table to facilitate site comparisons.  
If the hypothesis tests reveal site differences for either outcome, analyses will be 
performed to compare study sites in terms of participant baseline characteristics (e.g., 
demographics, medical history) as well as other variables that could influence clinical 
outcome such as eligibility criteria.  Analyses of primary and secondary endpoints will 
be conducted separately for each study site, and the results of the site comparisons will 
be used to inform how to interpret site-specific results. 
Subgroup analyses will be performed to determine if RV/LV diameter ratio and the 
proportion of patients experiencing major bleeding differ by demographic variables age, 


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race, and gender. Summary statistics (mean ± standard deviation, minimum, and 
maximum RV/LV diameter ratio, and the proportion of patients experiencing major 
bleeding) will be calculated for each demographic subgroup and presented in a table to 
facilitate group comparisons.  Regression models will be fit (linear regression for 
RV/LV diameter ratio, logistic regression for major bleeding) having each primary 
endpoint as the dependent variable and demographic group as the independent variable.  
A separate regression model will be fit for each combination of endpoint and 
demographic variable to formally test the hypothesis of subgroup differences in each 
primary endpoint.  
Sensitivity analyses will be undertaken to assess the impact of missing data for the 
primary endpoints.   The methods for this analysis are described in detail in Section 8 
of the Statistical Analysis Plan (THRO-STAT-2019-01), “Handling of Dropouts and 
Missing Data.” If subjects become COVID-19 positive after enrollment and during the 
study, a subgroup analysis will be performed. Refer to Statistical Analysis Plan (SAP) 
(THRO-STAT-2019-01) for additional details. 
20.3 
Analysis Populations 
All enrolled subjects who receive the study treatment will be included in the Intent-to-
Treat (ITT) population.  The ITT will consist of subjects who both provide informed 
consent to participate and have the BEC (or first of two BECs for bilateral PE) 
introduced into the sheath. The modified ITT (mITT) population are evaluable subjects 
defined as members of the ITT who have data available to assess the primary efficacy 
endpoint of reduction in RV/LV ratio as measured by contrast-enhanced chest CT 
(CTA) at screening and RV/LV ratio as measured by contrast-enhanced CTA at 48 
hours after completion of r-tPA treatment.  The patients comprising the mITT 
population are evaluable patients.  Members of the ITT population who remain in the 
study long enough to complete the 30-day follow-up period will comprise the Per-
Protocol (PP) population.   
The mITT population will be used to analyze the primary efficacy endpoint.  The ITT 
population will be used to analyze the primary safety endpoint, as well as all secondary 
safety and device endpoints that do not require 30 days of follow-up (e.g., device 
success, clinically relevant non-major bleeding, technical procedural complications).  
The PP population will be used to analyze secondary endpoints that require 30 days of 
follow-up: all-cause mortality, SAEs, AEs, UADEs, and recurrent PE through 30-day 
follow-up).   
Up to 125 subjects, in up to 20 sites, will be enrolled and treated, with the objective to 
have at least 100 subjects complete the 30-day follow-up period, and be included in the 
primary efficacy analysis.  Each site will have an enrollment cap such that no more than 
20% (n=20) of participants are enrolled at a single site.  


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21.0 
DATA SAFETY MONITORING BOARD 
A Data Safety Monitoring Board (DSMB) will be selected to review the study conduct, 
feasibility data, and safety data and will review all types of adverse events reported in this study 
and adjudicate as required.  The independent DSMB shall have the final adjudication for the 
events.  A data safety charter will be established and will be approved by the DSMB.  
Qualifications for the DSMB members, at a minimum, shall include current experience with 
catheter directed thrombolysis for the treatment of submassive pulmonary emboli, management 
of the patient post-treatment and extensive research experience. Adherence to the study stopping 
criteria in this protocol will also be included in the DSMB meetings in addition to following the 
charter.   
The DSMB shall have CEC responsibilities as well.  This hybrid committee include CEC 
responsibilities that include providing an independent expert review of data on clinical events 
based on protocol-specific definitions.  The CEC review ensures that events critical to the 
analysis of study results are assessed in a uniform manner. This facilitates reliable pooling of 
data within a trial and with predicate trials and improves the validity of comparisons with 
published data.  In addition to study endpoints, the CEC will provide assessment of other events 
or areas of concern at the request of the DSMB or Sponsor (e.g., device malfunction or failure, 
serious anticipated adverse events versus serious unanticipated adverse events). Member 
selection will be based on: 
 Balanced composition;  
 Relevant expertise;  
 Complete independence from the Sponsor and conduct of the trial;  
 Evaluation and documentation of any Conflict of Interest; and  
 Commitment to flexible schedules for the duration of the project life cycle. 
22.0 
STUDY STOPPING RULES 
22.1 
General Study Stopping Rules 
The Sponsor, DSMB, IRBs, regulatory authorities, or the principal investigators may 
make recommendations to terminate the study if the safety and well-being of the 
subjects are in jeopardy.  
If the study is terminated or suspended, prompt notification will be provided to all 
parties involved in the conduct of the study. 
Patient enrollment may be paused or terminated early if the Sponsor or DSMB, and/or 
CEC determines that the potential benefits of the investigational device are unlikely to 
outweigh the risks associated with continuation of the trial.   


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22.2 
Study Stopping Rules Related to Safety 
22.2.1 Intracranial Hemorrhage 
If three (3) patients undergoing the investigational procedure experience an 
unprovoked intracranial hemorrhage, confirmed by independent CEC/DSMB 
adjudication, and did not have a protocol violation such that he/she cannot be 
considered as representative of the intended patient population, the study shall 
be paused for re-evaluation, and may be stopped.  
22.2.2 Bleeding 
Should severe bleeding occur in 12 study subjects, the study will be paused, and 
the pharmacotherapy dosage and administration will be re-evaluated.  
22.2.3 Ad Hoc Criteria for CEC/DSMB Meetings 
1. If there are two (2) intracranial bleeds or eight (8) major bleeds within the 
first 60 subjects, an ad hoc meeting will occur for adjudication of the 
events.    
2. An ad hoc meeting will take place if any untoward event that, in the 
opinion of the chair, warrants an ad-hoc meeting. 
22.3 
Device Study Stopping Rules 
22.3.1 Device Related SAEs 
Should it be suspected that a device caused a serious adverse event, the serious 
adverse event will be adjudicated by the independent DSMB and the device 
shall be returned to the manufacturer.  A root cause analysis shall be performed. 
The DSMB will determine if the study should be stopped, temporarily 
suspended, or continued after each such event. 
22.3.2 Device Malfunctions and Non-conformances 
There are device malfunctions, or non-conformances, that may impact the 
patient and prevent treatment with an investigational device.  Upon 
commencement of enrollment, if there are device failures that prevent a total of 
five (5) subjects across two or more study sites (e.g. site 01 has three (3) device 
malfunctions, and site 05 has two (2) device malfunctions) from being treated 
in this study, the study shall be paused for re-evaluation of the device.  A root 
cause analysis will be performed to determine the cause(s) of the device failures 
and a corrective and preventative action will be implemented.   


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22.4 
Study Safety Reporting Requirements 
Reporting requirements for IDE studies will be followed.  The representative that will 
provide any necessary reports to FDA is the following:  
Diane Horwitz, PhD 
Eminence Clinical Research, Inc. 
Principal Regulatory Consultant 
dhorwitz@ecr-inc.com 
Phone: (703) 307-2921 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
THIS SPACE INTENTIONALLY LEFT BLANK 
 
 
 
 


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23.0 
VERSION CONTROL 
Add to table below for each protocol amendment 
PROTOCOL THRO-CLIN-2019-01 
VERSION 
SUMMARY OF THE CHANGE 
RATIONALE 
0.0 
Original for FDA Review 
Edited per FDA request to add in the following 
sentence: enrollment will not be stopped at the 
interim analysis of n=60 patients and full 
enrollment is planned for the study. 
N/A 
1.0 
Edited per FDA request to add in the following 
sentence: enrollment will not be stopped at the 
interim analysis of n=60 patients and full 
enrollment is planned for the study. [The rev 
number of this protocol reverts to the draft 
revision numbering in case there are additional 
changes to be made per FDA request.  The final 
version approved by FDA will be changed to 1.0 
once all final FDA requested changes are made 
and the IDE approval letter is received.] 
Make FDA requested 
changes and additional 
editorial changes. 
2.0 
Enrollment capped at 20% of sample size per 
FDA request, statistical changes made per FDA 
IDE approval letter February 6, 2020, and 
administrative changes. 
Implement changes in 
protocol according to 
recommendations in FDA 
IDE approval letter dated 
February 6, 2020. 
Administrative changes 
were done to add 
clarification. 
3.0  
Protocol amendment due to COVID-19, patient 
follow-up plan and Impact Assessment Form. 
Revise AE relatedness definitions and separate 
evaluation of device/drug from procedure 
events.  Address FDA recommendations in IDE 
approval letter for S001 dated April 2, 2020. 
New FDA Guidance on the 
conduct of clinical trials of 
medical products during the 
COVID-19 pandemic; 
capture more detail related 
to AE relatedness. 
4.0 
The 
protocol 
was 
amended 
after 
the 
CEC/DSMB 
kick-off 
meeting. 
 
The 
CEC/DSMB members asked for guidance from 
the steering committee to change the study 
stopping rules from percentages to patient 
numbers and to add ad hoc criteria for when the 
CEC/DSMB chairperson would call an ad hoc 
meeting.   
CEC/DSMB first meeting 
required changes to the 
stopping rules, criteria for 
ad hoc meetings, and to 
include emphasis on not 
cannulating arterial 
branches with the BEC at 
any time, add COVID-19 
exclusion, and 
administrative changes 
were made. 


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24.0 
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ultrasound-faclitated, catheter-directed, low-dose fibrinolysis for acute massive and 
submassive pulmonary embolism-SEATTLE II Study. J Am Coll Cardiol Interv. 
2015;8:1382–92. 
21. V.F. Tapson, K. Sterling, N. Jones, et al. A randomized trial of the optimum duration of 
acoustic pulse thrombolysis procedure in acute intermediate-risk pulmonary embolism: 
the OPTALYSE PE trial J Am Coll Cardiol Intv, 11 (2018), pp. 1401-1410 
22. Bashir™ Endovascular Catheter Instructions for Use, 2019 Thrombolex, Inc. 
23. Evans DC, Doraiswamy VA, Prosciak MP et al. Complications of pulmonary artery 
catheters: A comprehensive critical review.2009;98:199-208. 
24. http://www.calculator.net/body-surface-area-calculator.html accessed online January 
28, 2018. Archives of Internal Medicine 17 (6): 863-71.    
25. Ouriel K, Ouriel RL, Lim YJ, Piazza G, Goldhaber SZ.  Computed tomography 
angiography with pulmonary artery thrombus burden and right-to-left ventricular 
diameter ratio after pulmonary embolism. Vascular Online 2018;0(0):1-9. 
26. Qanaldi SD, Hajjam ME, Vieillard-Baron A et al. New CT Index to quantify arterial 
obstruction in pulmonary embolism: comparison with angiographic index and 
echocardiography.   American J of Radio.  2001;176:1415-20. 
27. Kaatz S, Ahmad D, Spyropoulos AC. Definition of clinically relevant non-major 
bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic 
disease in non-surgical patients: Communication form SCC of the ISTH. J of Thrombosis 
and Haemostasis. 2015;13:2119-36. 
28. Rosner B. Fundamentals of Biostatistics. 7th ed. Boston, MA: Brooks/Cole; 2011. 
29. A Prospective, Single-Arm, Multicenter Trial of Catheter-Directed Mechanical 
Thrombectomy for Intermediate-Risk Acute Pulmonary Embolism: The FLARE Study. 
Thomas Tu, M.D. On behalf of the FLARE Investigators. National PIs:  Kenneth 
Rosenfield, M.D. and Victor Tapson, M.D. SCAI Scientific Sessions: April 27, 2018 
30. Sista AK: The OPTALYSE PE Trial: Another Step Toward Understanding the Truth 
About Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism. JACC 
Cardiovasc Interv 2018, 11(14):1411–1413. 
31. FDA Guidance on Conduct of Clinical Trials of Medical Products during the COVID-19 
Pandemic. US Food and Drug Administration, March 2020; updated April 16, 2020. 
 
 
 


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25.0 
APPENDICES 
 
 


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Thrombolex, Inc. 
APPENDIX 25.1 REQUIRED STUDY PROCEDURES 
Test 
Pre- 
Procedure Procedure
Post- 
Procedure 
End of  
r-tPA 
Infusion 
24 Hrs 
Post-r-tPA 
Completed 
48 Hrs  
Post- r-tPA 
Completed 
72 Hrs  
Post- r-tPA 
Initiated 
Before 
Dis- 
charge 
30-day 
Follow-
up 
Visit Window 
≤ 48 Hrs 
of 
procedure 
 
 
 
±8  
Hrs 
±8 
Hrs 
-4 / +12 
Hrs 
-8  
Hrs  
±7  
Days 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Demographics and Medical History  
X 
 
 
 
 
 
 
 
 
Physical Examination 
X 
 
 
X 
X 
 
 
X 
  X7 
12 Lead ECG 
X 
 
 
 
 
 
 
 
 
CBC, INR1 
X 
 
 
 
X 
 
 
 
 
aPTT 
 X2 
 
X 
X 
 
 
 
 
 
CMP 
X 
 
 
 
 
 
 
 
 
BMP 
 
 
 
 
X 
 
 
 
 
Cardiac Biomarkers: Troponin, BNP 
X 
 
 
 
X 
 
 
 
 
Lower Extremity Venous DUS  
X 
 
 
 
 
 
 
 
 
Contrast Enhanced CTA of the Chest 
X 
 
 
 
 
X 
 
 
 
RV/LV Diameter Ratio with each CTA 
X 
 
 
 
 
X 
 
 
 
Eligibility Criteria 
X 
X 
 
 
 
 
 
 
 
Anticoagulation3  
X 
X 
X 
X 
X 
 
 
 
 
Ultrasound Guided Access 
 
X 
 
 
 
 
 
 
 
IR / Cath Lab: Invasive Hemodynamic Data4 
 
X 
 
 
 
 
 
 
 
IR / Cath Lab: r-tPA Pulse Sprays Administration 
 
X 
 
 
 
 
 
 
 
Bashir™ Endovascular Catheter(s) and r-tPA Use5 
 
X 
X 
X 
 
 
 
 
 
ICU:  PAS / PAD / Mean PA from Sheath(s) 
 
 
 
X 
 
 
 
 
 
ICU:  Mixed venous SvO2 from Sheath 
 
 
 
X 
 
 
 
 
 
r-tPA Infusion 
 
X 
X 
 
 
 
 
 
 
CO/CI by Modified Fick Method 
 
X 
 
X 
 
 
 
 
 
Medications (antiplatelet, anticoagulant, cardiac meds, and NSAIDs) 
X 
X 
X 
X 
X 
X 
  X6 
X 
X 
AEs / SAEs 
 
X 
X 
X 
X 
X 
  X6 
X 
X 
Contrast Enhanced Chest CTs to Core Lab 
X 
 
 
 
 
X 
 
 
 
COVID-19 Site Impact Assessment Form7 
 
 
 
 
 
 
  
 
 
1 INR is only required at baseline for patients on Coumadin (warfarin) and must be ≤ 1.5 prior to enrollment. If patient is eligible for the study, Coumadin will be discontinued temporarily for study purposes. 
2 Pre-procedure suggested aPTT be maintained at therapeutic dose.  Suggested aPTT during r-tPA administration decrease dose of UFH to 5-8 units/kg/hr up to a maximum of 1,000 units/hr. 
3 Refer to protocol section 7.1.4.  
4 Required: PAS, PAD, PA Mean, CO, CI, SpO2, SvO2 / at baseline, & post-infusion in the ICU. Swan-Ganz or angled pigtail may be used. CO= Modified Fick calculation.  
5 IV solution must be mixed according to protocol and infuse at the prescribed rate into target PA, or both PAs if bilateral PE. Infusion is to be administered over approximately 5 hours. 
6 If a study subject is discharged from the hospital prior to the 72-hour visit, a telephone follow-up in lieu of F2F follow-up will be conducted to verify that an AE and/or a change in medication has 
not occurred.  If either of these have occurred, additional detail will be collected over the phone and documented.  
7 If the study subject is unable to attend the visit in person, or in the event any study required test is omitted due to COVID-19, a protocol deviation form will be completed. 
 


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APPENDIX 25.2 RESCUE STUDY ANTICOAGULATION SCENARIOS  
 
 
 
 
 
 
 
 
 


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APPENDIX 25.3 INFORMED CONSENT FORM 
 
(The informed consent form is an appendix to the protocol and is provided separately in MS Word® 
format for site to edit according to IRB requirements) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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APPENDIX 25.4 CASE REPORT FORM 
 
(The case report form is an appendix to the protocol and is provided separately as a template for the 
electronic data capture database) 
 
 


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APPENDIX 25.5 CORE LAB PROTOCOLS 
 
(The core lab protocols are an appendix to the protocol and is provided separately.) 
` 
 
 


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APPENDIX 25.6 COVID-19 CONTINGENCY PLAN  
 
 
 


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STEP 1 Evaluate Impact to the Study 
The Impact Assessment Form will be completed by each site and submitted to the CRO representative. 
The investigational site operations will be evaluated to determine impact of the COVID-19 Pandemic.  
The Impact Assessment Form will be reviewed with the sponsor.   
STEP 2 Alternate Study Plans 
The CRO representative will review the Impact Assessment Form with the sponsor and will contact 
the site to confirm the site’s proposed appropriate alternative plan under the following conditions: 
 
1. Patient enrollment activities cannot be conducted in full compliance with the current 
protocol. 
If the impact affects the ability to complete any of the required activities for study enrollment, the 
site will not be activated, or enrollment will be suspended if the site was previously activated, until 
full operations can be restored. A Suspension of Study Due to COVID-19 Notice will be issued to 
the site. The investigator will submit the notice to the participating IRB.  
 
2. Patient follow-up cannot be conducted in full compliance with the current protocol. 
If the impact affects the follow-up visits for patients who have already been enrolled and treated 
with the study device, follow-up should be completed according to the protocol if possible. The 
Impact Assessment Form will be completed and submitted to the CRO representative. Based on 
the information given in the Impact Assessment Form, a follow-up plan for the site should be 
provided by the site on the Impact Assessment Form to the CRO. Additionally, the investigator 
will submit the completed Impact Assessment Form to the participating IRB. 
STEP 3 Restoration of Clinical Research Operations 
1. Resuming Clinical Research Operations 
As soon as the site can confirm that clinical research operations have resumed, or a due date is 
defined for resumption, the site will notify the CRO representative.  
 
2. Activation Letter 
The CRO, with approval from the study sponsor, will issue an Activation Letter or Addendum to 
the Suspension of Study Due to COVID-19 Notice with an effective date. This will restore the site 
to resume active status and return to all activities as defined per the protocol.   
 
 
 
 
 


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RESCUE STUDY COVID-19 SITE IMPACT ASSESSMENT FORM  
SECTION 1 
GENERAL IMPACT ASSESSMENT- ANSWER ALL QUESTIONS 
Site Name: 
 
Site 
Number: 
 
Investigator  
Name:  
 
Are any enrollment activities per the study protocol impacted? 
 No 
 Yes  
 
If yes, site may not be activated, or new 
enrollment may be suspended until full 
operation can be restored.  
Are any follow-up activities per the protocol impacted?  
 No 
 Yes 
 
 If yes, complete section 2 below 
Are monitoring activities impacted?  
 No 
 Yes 
 
If yes, complete section 3 below 
Are any enrolled subjects impacted?  
 No 
 Yes 
 
If yes, complete section 4 below 
Record an effective date when full operations will resume: 
 N/A  
     /     /20          
  (mm/dd/yyyy)  
Comments:  
SECTION 2 
 IMPACT ON FOLLOW-UP ASSESSMENTS – ANSWER ALL QUESTIONS 
Describe what follow-up assessments are impacted or cannot be conducted and if there is an alternate method to 
utilize (i.e. telephone, video conference or other) 
Assessment 
Affected? 
If YES, Explain Alternate Modified Plan 
24 Hours Post r-tPA Completion 
 No 
 Yes  
 N/A 
 
48 Hours Post r-tPA Completion   
 No 
 Yes  
 N/A 
 
72 Hours Post r-tPA Initiated   
 No 
 Yes  
 N/A 
 
Hospital Discharge 
 No 
 Yes  
 N/A 
 
30-Day Follow-up   
 No 
 Yes  
 N/A 
 
Page 1 of 2 
 


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Site Name: 
 
Site Number: 
 
Assessment 
Affected? 
If YES, Explain Alternate Modified Plan 
Concomitant Medications   
 No 
 Yes  
 N/A 
 
AE/SAE/UADE 
 No 
 Yes  
 N/A 
 
SECTION 3 
 IMPACT ON DATA MONITORING – ANSWER ALL QUESTIONS 
Assessment 
Affected? 
If YES, Explain Impact / Limitations 
Are there any impacts affecting 
monitoring at the site?  
(Obtaining access to the source 
documentation) 
 No 
 Yes   
 
Has a remote monitoring plan been 
implemented at the site as an 
alternative to on-site monitoring?   
 No 
 Yes   
 
SECTION 4 
 LIST OF ENROLLED SUBJECTS IMPACTED  
Subject # 
Plan 
 
 
 
 
 
 
 
 
 
 
 
 
Person 
Completing 
Form Printed 
Name: 
 
Signature 
& Date: 
___/___/20___ 
Physician 
Printed  
Name: 
 
Signature 
& Date: 
___/___/20___ 
Page 2 of 2 
 


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APPENDIX 25.7 RISK OVERVIEW 
 
 


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RISK OVERVIEW 
1. DESCRIPTION OF THE POPULATION 
 
Age 18 years of age to ≤ 75 years of age, have a filling defect in at least one main or lobar pulmonary 
artery as determined on contrast enhanced chest CT Scan (CTA), RV/LV diameter ratio ≥ 0.9 by 
contrast enhanced chest CT scan (CTA) as determined by the investigative site.  They must not 
have had a CVA or TIA within one (1) year, head trauma, active intracranial, or intraspinal disease 
within one (1) year prior to inclusion in the study, any active bleeding from a major organ within 
one (1) month prior to inclusion in the study, an intracranial condition(s) that may increase the risk 
of bleeding, a bleeding diatheses, a hematocrit less than 30, platelet count less than 100,000/μL, 
INR greater than 1.5 if currently on warfarin (Coumadin®), and each patient cannot have  an aPTT 
greater than 50 seconds in the absence of anticoagulants.  Please see section 6.3 for a complete list 
of eligibility criteria.   
2. OVERVIEW OF EFFICACY 
The Bashir™ Endovascular Catheter is intended for the controlled and selective infusion of 
physician-specified fluids, including thrombolytics, into the peripheral vasculature.  A First-in-man 
study was recently completed for the treatment of subjects with submassive pulmonary embolism.  
The study included administration of r-tPA through the BEC in the form of pulse sprays followed 
by an infusion over eight hours.  Subjects with unilateral embolism were administered a 2mg pulse 
spray through the basket of the BEC into the pulmonary artery (PA) followed by an infusion of 
10mg over approximately eight hours for a total dose of 12 mg.  Subjects with bilateral embolisms 
were administered 2mg pulse sprays into each pulmonary artery followed by an infusion of 5mg of 
r-tPA into each PA over eight hours for a total of 14mg.  Nine subjects were enrolled and treated.  
After 48 hours the RV/LV ratio decreased from 1.54  0.26 to 0.97  0.06 (p = .001: 95% CI = 
0.33 to 0.82: 36.7% reduction) as assessed by an independent core lab (Medical Metrics, Houston, 
TX). Thrombus burden measured by Modified Miller Index as assessed by the independent core 
lab (Medical Metrics, Houston, TX) decreased from 25.4  5.3 to 16.0  4.0 (p = .001: 95% CI = 
5.5 to 13.4: 37.1% reduction). 
Table 1. Independent Core LAB RV/LV Diameter Ratio 
Independent Core Lab RV/LV Diameter Ratio 
at 48 hours After Completion of r-tPA Infusion 
By Contrast Enhanced Chest CTA Compared to Baseline 
Baseline 
48 hours 
Difference 
(Baseline – 48 hrs) 
95% CI 
of difference 
T-test 
p-value 
Mean ± SD (n) 
Median [Range] 
Mean ± SD (n) 
Median [Range] 
Mean ± SD (n) 
Median [Range] 
N=8 
 
1.54  0.27 (8) 
1.48 [1.21-1.98] 
0.97  0.06 (8) 
0.96 [0.87-1.05] 
0.57 ± 0.29 (8) 
0.56 [0.18 - 1.02] 
0.33 – 0.82 
0.001 
 
 


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Table 2. Independent Core Lab Modified Miller Index Scores  
Independent Core Lab Modified Miller Index Scores 
at 48 hours After Completion of r-tPA Infusion 
By Contrast Enhanced Chest CTA Compared to Baseline 
Baseline 
48 hours 
Difference 
(Baseline – 48 hrs) 
95% CI 
of difference 
 
Mean ± SD (n) 
Median [Range] 
Mean ± SD (n) 
Median [Range] 
Mean ± SD (n) 
Median [Range] 
N=9 
T-test 
p-value 
25.4 ± 5.3 (9) 
28.0 [18.0 – 33.0] 
16.0 ± 4.0 (9) 
15.0 [11.0 – 22.0] 
9.4 ± 5.1 (9) 
8.0 [4.0 – 18.0] 
5.5 – 13.4 
0.001 
 
This first-in-man experience showed excellent efficacy results in all study subjects evident by the 
results from the independent core lab analyses for reduction in RV/LV diameter ratio and Modified 
Miller Index Scores.    
3. OVERVIEW OF SAFETY 
In the First-in-Man study mentioned above, the study results revealed an excellent safety profile 
for the BEC.  There were no adverse events or serious adverse events related to the device and 
there were no adverse events or serious adverse events related to the r-tPA.   
4. POTENTIAL RISKS AND RISK MITIGATION 
 
A. Potential Risks to Research Subjects 
The potential risks in the RESCUE study related to the device can be categorized in the following 
way in Table 3 below. These include basic safety, device related SAEs, device related AEs, 
procedure related complications due to the investigation, risks associated with the study itself, and 
risks from false-positive or false negative results for diagnostics.  The last category is not 
applicable, as the RESCUE study is the delivery of a therapy.   
 
 
 
 
THIS SPACE INTENTIONALLY LEFT BLANK 
 
 
 
 


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Table 3.  Definitions of Types of Risks 
Risk Types  
Definition 
Basic Safety 
Protection against physician hazards, which should be addressed and 
mitigated with a reasonable level of certainty. 
Device Related SAEs 
Events attributable to the investigational use of the device which produce 
an injury that is life threatening, results in permanent impairment or 
damage to the body, or requires medical or surgical intervention to 
prevent permanent harm to the body. 
Device Related AEs  
(non-serious) 
Events attributable to the investigational use of the device which do not 
produce an injury or illness that is life-threatening, does not result in 
permanent impairment or damage to the body, or does not require 
medical or surgical intervention to prevent permanent harm to the body. 
Procedure-related 
Complications Due to 
the Investigation 
This includes not just the device use, but risks related to the investigation 
itself to which the subject would otherwise not be exposed, e.g. risk of 
anesthesia during procedures involving an investigational device. 
Risks associated with 
the study itself 
Risks the subject may be exposed to that do not directly result from use 
of the device and would not be expected as part of usual care outside of 
the investigational setting. Examples include additional procedures (such 
as medical imaging) for ascertainment of study endpoints. 
Risk from false-
positive or false-
negative results for 
diagnostics 
N/A – The BEC is not a diagnostic device. 
 
A description and analysis of the risks to research subjects related to the device and the study are 
listed below for each category in Table 3 above.  
Basic Safety: Physician hazards may include exposure to blood and body fluids, which is standard 
for any invasive procedure in the interventional lab.  Physicians and staff wear personal protective 
equipment to prevent exposure.  This is not unique to the investigational device in the RESCUE 
study.  There is no electrical power required for this device, so electrical safety issues are not 
relevant.   
Device Related SAEs or Device Related AEs (Non-Serious):  Device related SAEs may include 
allergic reactions, hematoma at access site, hemorrhage, intimal damage, ischemia, pain and 
tenderness, vascular thrombosis, vessel perforation, and vessel spasm.  These adverse events will 
be categorized as serious only if one of the following conditions applies:  
An adverse event is any undesirable experience associated with the use of a medical product in a 
patient. The event is serious and will be collected when the patient outcome is: 


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1. Death 
2. Life-threatening -  Report if suspected that the patient was at substantial risk of 
dying at the time of the adverse event or use or continued use of the device or other 
medical product might have resulted in the death of the patient. 
3. Hospitalization (initial or prolonged) - Report if admission to the hospital or 
prolongation of hospitalization was a result of the adverse event. 
Emergency room visits that do not result in admission to the hospital should be 
evaluated for one of the other serious outcomes (e.g., life-threatening; required 
intervention to prevent permanent impairment or damage; other serious medically 
important event). 
4. Disability or Permanent Damage - Report if the adverse event resulted in a 
substantial disruption of a person's ability to conduct normal life functions, i.e., 
the adverse event resulted in a significant, persistent or permanent change, 
impairment, damage or disruption in the patient's body function/structure, physical 
activities and/or quality of life. 
5. Congenital Anomaly/Birth Defect - Report if you suspect that exposure to a 
medical product prior to conception or during pregnancy may have resulted in an 
adverse outcome in the child. 
6. Required Intervention to Prevent Permanent Impairment  or Damage (Devices) - 
Report if you believe that medical or surgical intervention was necessary to 
preclude permanent impairment of a body function, or prevent permanent damage 
to a body structure, either situation suspected to be due to the use of a medical 
product. 
7. Other Serious (Important Medical Events) - Report when the event does not fit the 
other outcomes, but the event may jeopardize the patient and may require medical 
or surgical intervention (treatment) to prevent one of the other outcomes. 
Examples include allergic bronchospasm (a serious problem with breathing) 
requiring treatment in an emergency room, serious blood dyscrasias (blood 
disorders) or seizures/convulsions that do not result in hospitalization. The 
development of drug dependence or drug abuse would also be examples of 
important medical events. 
 
Procedure Related Complications Due to the Investigation: These complications are unrelated 
to the BEC and may include access site pseudoaneurysm, anemia, arrhythmia, bleeding requiring 
blood transfusion, cardiac arrest, death, ecchymosis, hematuria, hemodynamic instability, heparin 
induced thrombocytopenia, infection, pain at access site, perforation, pneumothorax, pulmonary 
infarct, shock, skin necrosis (if on warfarin). 
Risks Associated with the Study Itself: The risks associated with the study itself are discussed 
below. The additional risks are not expected to be above standard of care.   
 


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B. 
Risk Mitigation and Risk Minimization 
 
1. 
Basic Safety:  There is no expected increase in basic safety concerns.  The sites selected 
are highly experienced in the protection from blood borne pathogens and the use of the 
BEC does not increase this risk.  Additionally, regarding radiation exposure for the staff 
and physicians, the procedure times are short compared to some interventional 
procedures.  The procedure time in the First-in-Man study from local anesthetic to last 
wire out of the patient was a mean of 57 minutes (with a range of 43 minutes to 72 
minutes). 
 
2.  Device Related SAEs:   Allergic reaction – Staff monitor the subject for reactions and 
medicate the study subject accordingly.   
Hematoma at access site – This is potentially due to the venous stick technique.  We are 
minimizing the potential for a hematoma by requiring the use of ultrasound guidance at 
the time of obtaining access either in the femoral vein or the internal jugular vein.   
Hemorrhage – We are preventing hemorrhage by only selecting physicians in the study 
who are experienced in PM-CDT and hemodynamic monitoring.  Having this expertise 
prior to study site selection will minimize the possibility of hemorrhage due to 
perforation.  Additionally, the dose of r-tPA is less than the dose in other studies.  The 
RESCUE protocol requires a certain heparin dose and lovenox dose.  This is to prevent 
over anti-coagulation in the study subjects.   
Intimal damage – There is the potential for intimal damage with any interventional 
procedure within the vasculature.  This is minimized by the use of the long sheaths and 
the assessment under fluoroscopy of the basket expanding in the pulmonary vasculature.  
Ischemia may be minimized by shorter procedure times, shorter time to improved 
ventilation and perfusion in the pulmonary embolism patient.   
Vascular thrombosis is prevented with anti-coagulation.   
Vessel perforation is prevented by choosing experienced operators who have extensive 
experience with catheter-based therapies and PM-CDT.   
Vessel spasm may occur but can be minimized with highly experienced operators.  The 
potential for spasm is much less in venous treatment than with arterial treatment.   
 
3. 
Procedure-Related Complications: The procedure-related complications listed above 
will be mitigated by selecting experienced operators, lab staff, and research staff.  In the 
First-in-Man study use in the pulmonary artery, the device was inserted through a long 
sheath that was placed in the pulmonary artery prior to the BEC insertion.  This allows 
for easy insertion from the sheath outside of the patient into the right side of the heart 
and the pulmonary artery within the sheath.  The physicians place the device in the 
interventional lab by advancing it through the sheath, and by viewing the radiopaque 
infusion basket under fluoroscopy.  The entire basket is made of nitinol components; 
therefore, the entire basket is radiopaque under fluoroscopy.  This same technique will 
be used in the RESCUE study.  This minimizes the possibility of the BEC causing 
damage to the vasculature when being inserted through the vasculature.   
 


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4. Risks Associated with the Study Itself: The CTA imaging is a requirement for the 
primary endpoint analysis.  Site staff will be trained on the image acquisition protocol 
and they will be qualified in advance to ensure they have the proper imaging equipment 
to perform the tests.  Both of these requirements should help reduce the exposure that 
could result from redoing study-required imaging.  If the 48-hour CTA is not standard 
of care, one extra CTA would be required for the study subject, a small increase in 
radiation exposure. The in-lab imaging is standard of care for the practicing 
interventionalist.  
 
C. Summary 
  
Overall, the actions taken to mitigate risks include the following: 
1. 
Select qualified sites and investigators that meet strict criteria; 
2. 
Provide detailed didactic and hands-on device training; 
3. 
Ensure all investigators inspect the device and prep the device and test it for 
functionality before use; 
4. 
Provide core lab requirement training; 
5. 
Support study procedure as needed with procedure and research experts to guide 
physicians and staff. 
 
5. POTENTIAL BENEFITS 
The potential benefit from BEC treatment of pulmonary embolism is effective treatment for the 
condition, as reduction in clot burden has been demonstrated by RV/LV ratio reduction and 
decrease in refined Modified Miller Score in the First-in-Man study.  Additionally, there may be a 
lower bleeding risk with the BEC because of low r-tPA dose and shorter infusion times compared 
to what was required in SEATTLE II.  The design of the BEC creates multiple channels where 
blood can flow to increased exposure of the clot surface area to fluid, endogenous lytics, exogenous 
lytics (e.g., r-tPA), thus potentially having a greater reduction in clot burden than other PM-CDT 
devices that create only a single channel.  This benefit remains to be seen in a larger population; 
therefore, the RESCUE study is being conducted.   
6. CONCLUSIONS 
As demonstrated in the First-in-Man study, the potential benefits outweigh the risks of treating 
patients with the BEC.