Clinical trial NCT03927508
Conditions: Pulmonary Embolism
Keywords: Pulmonary Embolism
Sponsor: Thrombolex, Inc.
Start date: 2019-03-14; Completion date: 2020-01-23
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The Bashir™ Endovascular Catheter is a device intended for the localized infusion of therapeutic agents into the pulmonary artery and peripheral vasculature.

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.

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

Protocol documents:
Prot_SAP_000.pdf: 
First-in-Man IND Study            
Confidential               
 
IND Number: 140347 
First-in-man IND Protocol THRO-CLIN-2018-01     Version 6.0  September 14, 2019          Page 1 of 53 
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 First – In – Man Study to Assess the Safety and 
Feasibility of The Bashir™ Endovascular 
Catheter for the Treatment of Acute Pulmonary 
Embolism 
 
 
Protocol Number 
THRO-CLIN-2018-01 
 
 
IND Number 
140347 
 
 
Study Phase 
Phase I – First-in-Man Study 
 
 
Drug Development Phase 
Post-Market - FDA approved drug administered in this study 
 
 
Study Sponsor 
Thrombolex, Inc. 
75 Britain Dr, New Britain, PA 18901 
 
 
Current Protocol Version 
6.0 
 
 
Version Date 
September 14, 2019 
 
 
Previous Version 
5.0  
 
 
Principal Investigators 
Kenneth Rosenfield MD – Interventional Cardiologist 
 
Akhilesh Sista MD – Interventional Radiologist 
 
 
Data Safety Monitor 
Gregory Piazza, MD, MS 
 
 
SAE Reporting 
Diane Horwitz, PhD 
Eminence Clinical Research, Inc. 
 
 
Sponsor Approval 
Approval Date 
Brian G. Firth, MD, PhD, MBA, FACC 
September 16, 2019 
Chief Scientific Officer 
 
Thrombolex, Inc. 
 
New Britain, PA 
 
 
 
 
 


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IND Number: 140347 
First-in-man IND Protocol THRO-CLIN-2018-01     Version 6.0  September 14, 2019          Page 2 of 53 
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 
9 
3.0 
TERMS AND DEFINITIONS 
10 
4.0 
BACKGROUND AND RATIONALE 
13 
4.1 Clinical Problem  
13 
4.2 Current Treatment Options 
13 
4.3 Study Rationale   
14 
5.0 
INVESTIGATIONAL DEVICE 
16 
Figure 1. Bashir Endovascular Catheter 
16 
Figure 2. Bashir Endovascular Catheter with Basket Expanded 
16 
Table 1. Bashir™ Endovascular Catheter Dimensions 
16 
6.0 
STUDY DESIGN 
17 
6.1 Study Objective  
17 
6.2 Primary and Secondary Endpoints 
17 
 
6.2.1 Primary Endpoints 
17 
 
6.2.2 Secondary Endpoints 
17 
6.3 Eligibility Criteria 
18 
 
6.3.1 General Inclusion Criteria 
18 
 
6.3.2 General Exclusion Criteria 
18 
6.4 Study Duration   
19 
 
6.4.1 Enrollment  
19 
 
6.4.2 Follow-up   
19 
 
6.4.3 Complete Study Period 
19 
 
6.4.4 Subject Participation 
19 
7.0 
METHODOLOGY 
20 
7.1 Pre-Procedure Tests Within 48 Hours Pre-Procedure 
20 
 
7.1.1 Laboratory Tests 
20 
 
7.1.2 Imaging   
20 
 
7.1.3 Assessments 
21 
 
7.1.4 Anticoagulation 
21 
 
7.1.5 Patients Receiving Lovenox for Treatment of Pulmonary Embolism 
21 
 
7.1.6 Data Collection 
21 
8.0 
IR SUITE/CATH LAB STUDY PROCEDURES 
22 
 
8.1 Required Accessories and Supplies 
22 
 
8.1.1 Accessories to be provided by the IR suite/Cath lab 
22 
 
8.1.2 Procedure Supplies Provided by the Sponsor 
23 
 
8.2 Baseline Hemodynamic Readings 
23 
9.0 
BASHIR™ ENDOVASCULAR CATHETER INVESTIGATIONAL PROCEDURE 23 
 
9.1 Baseline Readings - Summary of Procedure Stps 
23 
 
9.2 Bashir Endovascular Catheter Use – Procedure Steps 
24 
 
9.3 r-tPA Administration 
24 
 
9.3.1 Part 1 – r-tPA Pulse Spray - In the IR suite/Cath lab through the BEC 
24 
Table 2. r-tPA Doses and Mixtures for Pulse Sprays and Infusions through the BEC  25 
 
9.3.2 Part 2 – r-tPA Infusion and Anticoagulation –  Site/Cath lab r-tPA Infusion 27 
 
9.4 Intra-procedure Data Collection Requirements 
28 


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part without written permission from Thrombolex, Inc. 
 
9.5 Preparation in IR suite/Cath lab for Transfer to ICU 
28 
10.0 POST-PROCEDURE PATIENT MANAGEMENT AND TESTS 
29 
 
10.1 r-TPA Infusion – Intensive Care Unit 
29 
 
10.2 Return to The IR suite/Cath lab at The Completion of Infusion 
30 
 
10.3 Tests Required at End of Infusion(s) and 24 Hours After r-tPA Infusion 
31 
 
10.3.1 Laboratory Tests and Other Tests 
31 
 
10.3.2 Imaging   
31 
 
10.3.3 Assessments 
31 
 
10.3.4 Data Collection 
31 
 
10.4 Tests Required 48 Hours Following End of r-tPA Infusion 
32 
 
10.4.1 Imaging   
32 
 
10.4.2 Assessments 
32 
 
10.4.3 Data Collection 
32 
 
10.5 Anticoagulation and Sheath Removal 
32 
 
10.5.1 Heparin Infusion 
32 
 
10.5.2 FDA Approved Anticoagulation Regimen 
32 
 
10.5.3 Sheath Removal 
32 
 
10.6 Tests Required 72 Hours (+12 hours) Following Start of r-tPA Administration 
33 
 
10.6.1 Assessments 
33 
 
10.6.2 Data Collection 
33 
 
10.7 Tests Required Just Prior to Hospital Discharge 
33 
 
10.7.1 Assessments 
33 
11.0 30-DAY FOLLOW-UP VISIT POST PROCEDURE 
33 
 
11.1 Assessments 
33 
 
11.2 Data Collection 
33 
12.0 ANTICIPATED ADVERSE EVENTS 
33 
 
12.1 Bashir Endovascular Catheter Anticipated Adverse Events 
34 
Table 3. Anticipated Adverse Events Related to the Investigational Device18 
34 
 
12.2 r-tPA Anticipated Adverse Events 
34 
Table 4.  Anticipated Adverse Events Related to r-tPA Infusion15 
34 
 
12.3 Anticipated Adverse Events Related to the Procedure 
34 
Table 5. Anticipated Adverse Events Related to the Procedure20 
34 
13.0 ADVERSE EVENT REPORTING 
35 
 
13.1 Serious Adverse Events and Serious Suspected Adverse Reactions 
35 
 
13.2 Unexpected Adverse Event or Unexpected Suspected Adverse Reaction 
36 
 
13.3 Adverse Event Documentation 
36 
 
13.4 Adverse Event Relatedness 
36 
Table 6. Adverse Event Categories of Device Relatedness 
36 
 
13.5 Investigator SAE Reporting Requirements 
37 
14.0 REGULATORY REQUIREMENTS 
37 
 
14.1 Investigator Responsibilities 
38 
 
14.2 Sponsor Responsibilities 
40 
 
14.3 Record Retention 
41 
15.0 DEVICE AND DRUG ACCOUNTABILITY 
41 
 
15.1 Bashir™ Endovascular Catheter Packaging for the IR suite/Cath lab 
41 
 
15.2 Device Accountability 
41 
 
15.3 Drug Accountability 
41 
16.0 STATISTICAL CONSIDERATIONS 
41 


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16.1 Sample Size Justification 
41 
 
16.2 Data Analysis 
42 
 
16.3 Data Entry 
42 
17.0 DATA SAFETY MONITOR 
42 
18.0 STUDY STOPPING CRITERIA 
42 
 
18.1 General Study Stopping Rules 
42 
 
18.2 Safety Study Stopping Rule 
43 
 
18.3 Efficacy Study Stopping Rule 
43 
 
18.4 Device Study Stopping Rules 
43 
 
18.5 Study Safety Reporting Requirements 
43 
19.0 VERSION CONTROL 
44 
20.0 REFERENCES 
45 
21.0 APPENDICES 
47 
APPENDIX 21.1  REQUIRED STUDY PROCEDURES 
48 
APPENDIX 21.2 
STUDY SCHEMA 
49 
APPENDIX 21.3 
INFORMED CONSENT FORM 
50 
APPENDIX 21.4    CASE REPORT FORM 
52 
APPENDIX 21.5  CORE LAB PROTOCOLS 
53 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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part without written permission from Thrombolex, Inc. 
1.0 PROTOCOL SYNOPSIS 
STUDY NAME 
First – in – man study to assess the safety and feasibility of the Bashir™ 
Endovascular Catheter for the treatment of acute pulmonary embolism. 
PROTOCOL NO. 
THRO-CLIN-2018-01 
PROTOCOL DATE 
September 14, 2019 
SPONSOR 
Thrombolex, Inc. New Britain, PA 
CO-PRINCIPAL 
INVESTIGATORS 
Kenneth Rosenfield MD – Interventional Cardiologist 
Akhilesh Sista MD – Interventional Radiologist 
STUDY DEVICE 
The Bashir™ Endovascular Catheter is a device intended for the localized 
infusion of therapeutic agents into the pulmonary artery and peripheral 
vasculature. 
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 basket infusion port with 10cc 
syringes.  
Unilateral PE: 2mg total in 20cc administered in two (2) 10cc syringes. 
Bilateral PE: 4 mg 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 10mg in 750cc 0.9% NaCl infused at 1.27mg/hr at an 
infusion rate of 95cc/hr, through the Bashir™ Endovascular Catheter until 
complete. Total r-tPA dose (pulse spray and infusion) is 12.0mg. 
Bilateral PE: r-tPA 5mg in 500cc 0.9% NaCl infused at 0.65mg/hr at an infusion 
rate of 65cc/hr bilaterally through each Bashir™ Endovascular Catheter, until 
complete for a total r-tPA dose of 1.3mg/hr, 0.65mg per hour through each 
catheter. Total r-tPA dose (pulse spray and infusion) is 14.0mg. 
ANTICOAGULANT 
DOSAGE AND 
ADMINISTRATION 
Pre-procedure: Unfractionated heparin will be administered IV to prolong the 
aPTT pre-procedure (suggested range 60-80 seconds). 
Note: Use of enoxaparin (Lovenox®) is permitted pre-procedure for the treatment 
of PE. If Lovenox is given, then catheter directed thrombolysis procedure is to 
start no sooner than 12 hours after the last Lovenox dose was administered. 
Procedure:  Heparin infusion will be discontinued upon arrival in the IR/Cath lab.  
ACT will be monitored in IR/Cath Lab and heparin boluses administered to 
achieve ACT ≥ 200 seconds. 
During r-tPA Infusion: Heparin infusion will be restarted post-procedure and 
administered through the side arm of each sheath to prolong the aPTT (suggested 
range 40-60 seconds).  
Post r-tPA Infusion: Upon completion of r-tPA infusion, maintain patency 
through the BEC by replacing r-tPA with heparinized saline TKO using the 
infusion pump.  Starting 45 minutes (± 15 minutes) after the r-tPA completion, 
administer Lovenox 1mg/kg sub-Q every 12 hours (±30 minutes) through the 
completion of the 48-hour CTA.  


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part without written permission from Thrombolex, Inc. 
 1.0 PROTOCOL SYNOPSIS (CONTINUED) 
POPULATION 
Patients 18 years of age or older 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. 
STUDY 
OBJECTIVE 
Assess the safety and feasibility of the Bashir™ Endovascular Catheter for the 
administration of low dose thrombolytic for acute submassive pulmonary 
embolism. 
SAMPLE SIZE 
Up to ten (10) subjects will be enrolled and treated. 
SITES 
Up to five (5) sites will be qualified to participate in this study. 
PRIMARY 
ENDPOINTS 
1.  Safety: Major bleeding, as defined by International Society of Thrombosis and 
Hemostasis (ISTH), within 72 hours of initiation of r-tPA administration.  
Bleeding criteria are as follows: Major Bleeding in Non-Surgical Patients 
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 g/dL (1.24 mmol/L) or 
more or leading to transfusion of two or more units of whole blood or red 
cells. 
2. Feasibility: Device success defined as the ability to use the Bashir™ 
Endovascular Catheter as described in this protocol. 
SECONDARY 
ENDPOINTS 
1. All-cause mortality at hospital discharge through 30-day follow-up. 
2. SAEs through 30-day follow-up. 
3. Anticipated (non-serious) adverse events (AEs) through 30-day follow-up. 
4. Recurrent PE through 30-day follow-up.  
5. 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.  
6. Technical procedural complications. 
7. RV/LV end diastolic diameter ratio at 24 hours after completion of r-tPA 
infusion compared to baseline, by echocardiogram.  
8. RV/LV diameter ratio at 48 hours after completion of r-tPA infusion, by 
contrast-enhanced chest CTA compared to baseline. 
                                          Continued on next page 
 
 
 


First-in-Man IND Study            
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IND Number: 140347 
First-in-man IND Protocol THRO-CLIN-2018-01     Version 6.0  September 14, 2019          Page 7 of 53 
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part without written permission from Thrombolex, Inc. 
1.0 PROTOCOL SYNOPSIS (CONTINUED) 
SECONDARY 
ENDPOINTS 
(CONTINUED) 
9. Modified Miller Index at 48 hours post completion of the r-tPA infusion as 
compared to baseline by contrast-enhanced chest CTA. 
10. Systolic PA pressure measured at completion of infusion and compared to 
baseline. 
11. Cardiac output (CO by modified Fick calculation) and cardiac index (CI) 
following completion of infusion, upon return to the IR suite/Cath lab 
compared to baseline. 
ELIGIBILITY 
CRITERIA 
Inclusion Criteria 
1. Willing and able to provide informed consent; 
2. 18 years of age and less than 75 years of age; 
3. PE symptom duration ≤ 14 days; 
4. Filling defect in at least one main or lobar pulmonary artery as determined 
by contrast enhanced chest CT; 
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. Cerebrovascular Accident (CVA) or transient ischemic attack (TIA) within 
one (1) year; 
2. Head trauma, or other active intracranial, or intraspinal disease within 
one (1) year; 
3. Recent (within one month) or active bleeding from a major organ;  
4. Intracranial condition(s) that may increase the risk of bleeding (e.g., 
neoplasms, arteriovenous malformations, or aneurysms); 
5. Patients with bleeding diathesis; 
6. Hematocrit < 30%; 
7. Platelets < 100,000/μL; 
8. INR > 1.5; 
9. aPTT > 50 seconds in the absence of anticoagulants;  
10. Major surgery within fourteen (14) days;  
11. Serum creatinine > 2.0 mg/dL;  
12. Clinician deems high-risk for catastrophic bleeding;  
13. History of heparin-induced thrombocytopenia (HIT);  
14. Pregnancy; 
15. Systolic blood pressure < 90 mmHg for > 15 minutes;  
16. Any vasopressor support; 
17. Cardiac arrest (including pulseless electrical activity and asystole) 
requiring active cardiopulmonary resuscitation (CPR);  
18. Evidence of irreversible neurological compromise;  
19. Life expectancy < one (1) year; 
20. Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days 
prior to inclusion in the study; 
                                    Continued on next page 
 


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IND Number: 140347 
First-in-man IND Protocol THRO-CLIN-2018-01     Version 6.0  September 14, 2019          Page 8 of 53 
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. 
1.0 PROTOCOL SYNOPSIS (CONTINUED) 
ELIGIBILITY 
CRITERIA 
(CONTINUED) 
21. Use of non-vitamin K oral anti-coagulants (NOACs), such as 
rivaroxaban, apixaban, dabigatran, edoxaban within 48 hours prior to 
inclusion in the study;  
22. Use of enoxaparin sodium injection (Lovenox®) within 12 hours of 
procedure start time; 
23. Profound bradycardia requiring a temporary pacemaker and/or 
inotropic support; 
24. Previous enrollment in this study; 
25. Morbidly obese (BMI >45 kg/m2) patient who by the judgement of the 
investigator is high risk for bleeding; 
26. Absolute contraindication to anticoagulation; 
27. Uncontrolled hypertension; 
28. Currently participating in another study; 
29. 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 eleven (11) months. 
DATA SAFETY 
MONITOR 
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 / ECHO 
INDEPENDENT 
CORE LAB 
Medical Metrics, Inc. 
2121 Sage Road 
Suite 300 
Houston, TX 77056 
 
 
 


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part without written permission from Thrombolex, Inc. 
2.0 STUDY CONTACTS 
CO-PRINCIPAL INVESTIGATOR 
CO-PRINCIPAL INVESTIGATOR 
Interventional Radiologist 
Interventional Cardiologist 
Akhilesh K. Sista MD  
Kenneth Rosenfield MD 
NYU Langone I 
Massachusetts General Hospital  
660 1st Avenue Room 318  
 55 Fruit St. #800 
New York, NY  10016 
Boston, MA 02114 
Phone: 212-746-2771 
Phone: 617-726-2256 
Email: asista@gmail.com 
Email: krosenfield1@mgh.harvard.edu 
SPONSOR 
Thrombolex, Inc. 
Brian G. Firth, MD, PhD, MBA, FACC 
Chief Scientific Officer 
Phone: 215-499-8184 
Email: Brian@Thrombolex.com 
STUDY MANAGEMENT / DATA MONITORING / EDC 
Eminence Clinical Research, Inc. 
Pamela DiCamillo, LVN, CCRC 
13521 Northgate Estates Drive, Suite 150 
Colorado Springs, CO 80921 
Phone:  719-400-7463 
e-Fax: 720-206-0985 
Email: Pdicamillo@ecr-inc.com 
INDEPENDENT CTA AND ECHOCARDIOGRAPHY CORE LAB 
Medical Metrics, Inc. 
Daniel A. Auger, PhD 
Client Services Manager (CV) 
2121 Sage Road, Suite 300  
Houston, Texas 77056  
Phone: 713-850-7500 Ext. 241 
Fax: 713-850-7527  
Email:  dauger@medicalmetrics.com 


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part without written permission from Thrombolex, Inc. 
3.0 TERMS AND DEFINITIONS 
TERM 
DEFINITION 
AE 
Adverse Event - An adverse event is any untoward medical occurrence 
associated with the use of a drug in humans, whether or not considered drug 
related (21 CFR 312.32(a)). 
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 to 
diagnose heart failure quickly.  
BSA 
Body Surface Area - Du Bois formula: BSA = 0.007184 × W0.425 × H0.725 
Du Bois D, Du Bois EF (Jun 1916). A formula to estimate the approximate 
surface area if height and weight are known.21 This formula is not required if 
sites have ability to calculate BSA per other standard method.  
CBC  
Complete Blood Count 
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 
CMP 
Complete Metabolic Panel 
CTA 
Computerized Tomography Angiogram 
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. 
DSM 
Data Safety Monitor: Physician experienced in the treatment of PE with 
mechanical thrombolysis will adjudicate all adverse events in this study. 
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 SaO2) 
CvO2 = (1.36 x Hgb x SvO2) 
This Modified Fick calculation is required in this protocol. 
 


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part without written permission from Thrombolex, Inc. 
3.0 TERMS AND DEFINITIONS (CONTINUED) 
HIT 
Heparin Induced Thrombocytopenia 
Hrs 
Hours 
IJ 
Internal Jugular 
INR 
International Normalized Ratio 
LCFV 
Left Common Femoral Vein 
Modified Miller 
Index (MMI) 
To deﬁne the CT obstruction index, the arterial tree of each lung is regarded 
as having 10 segmental arteries (3 to the upper lobes, 2 to the middle lobe and 
the lingula, and 5 to the lower lobes).   The presence of embolus in a 
segmental artery is scored 1 point, and emboli in the most proximal arterial 
level are scored a value equal to the number of segmental arteries arising 
distally. To provide additional information about the residual perfusion distal 
to the embolus, a weighting factor is assigned to each value, depending on the 
degree of vascular obstruction.  This factor is equal to zero, when no thrombus 
is observed; 1, when partially occlusive thrombus is observed; or 2, with total 
occlusion. Thus, the maximal CT obstruction index is 40 per patient.22   
PAD 
Pulmonary Artery Diastolic Pressure 
PaO2 
Partial Pressure of Arterial Oxygen 
PAP 
Pulmonary Artery Pressure 
PAS 
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. 
RV/LV 
Right Ventricular / Left Ventricular 
SAEs 
Serious Adverse Event - An adverse event or suspected adverse reaction is 
considered "serious" if, in the view of either the investigator or sponsor, it 
results in any of the following outcomes: 
1. Death  
2. Life-threatening adverse events 
Continued on next page 
 
 


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part without written permission from Thrombolex, Inc. 
3.0 TERMS AND DEFINITIONS (CONTINUED) 
SAEs  
(Continued) 
3. 
Inpatient Hospitalization or Prolongation of existing hospitalization 
4. 
A Persistent or Significant Incapacity or a substantial disruption in the 
ability to conduct normal life functions, or 
5. 
Congenital Anomaly or Birth Defect. 
6. 
Important medical events that may not result in death, be life-
threatening or require hospitalization, may be considered serious when 
based upon appropriate medical judgement they may jeopardize the 
patient or may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition.    
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   
Troponin I 
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 cTnI levels support the diagnosis of severe 
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, patients 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 work-ups 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/hour over 12 hours (bilateral PE). This 
treatment methodology achieved an absolute reduction in RV:LV ratio of 0.42 (±0.36), the mean 
baseline was 1.55 (±0.39) and at 48 hours 1.13 (±0.2).15,17  
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 
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 first-in-man study will utilize the Bashir™ Endovascular Catheter to administer catheter 
directed thrombolysis in patients with submassive PE who have consented and meet all 
eligibility criteria.  The Bashir™ catheter represents a new methodology for localized catheter-
based delivery of thrombolytics. The thrombolytic to be used in this study is r-tPA (Genentech 


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Corporation, South San Francisco, USA).16 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.17 The design of the Bashir 
Endovascular Catheter with the multiple infusion limbs creating a basket-like formation when 
expanded, provides 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, 
presented at ISET, February 6, 2018, 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. 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.18  
 
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.17 We therefore 
propose to utilize the following regimen: r-tPA 2mg in 20 cc administered in 1mg and 10cc 
increments x 2 into the PA for a total of 2 pulse sprays into the infusion basket via its infusion 
port on the handle, using a syringe, followed by a 10mg infusion at  1.27mg per hour until 
complete for unilateral PE, and 5mg infusion into each pulmonary artery for bilateral PE, at 
0.65mg/hour until complete for a total dose of 1.3mg/hour for bilateral PE.  This is a total of 12 
mg over approximately 8 hours (pulse spray 1mg x 2 sprays = 2mg plus infusion at 1.27mg/hour 
x 7.87 hours (approximately 8 hours = 12mg) for unilateral PE. For bilateral PE, we propose to 
administer the same pulse spray and one-half of the infusion dose into each PA to total the 
unilateral infusion dose, for a total of 14mg administered including the pulse sprays and the 
infusions. 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.  Additionally, an efficacy study 
stopping rule has been established for this study based on the reduction in RV:LV diameter ratio 
observed in the SEATTLE II study (0.42-0.36).  The minimal reduction of 0.06 in SEATTLE II 
formed the basis for the efficacy study stopping rule for this study.  If a reduction is less than 
0.06 (refer to Section 18.3) in the first three patients, the study will be paused to re-evaluate the 
r-tPA dosage and administration. 
 


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5.0 INVESTIGATIONAL DEVICE 
The Bashir™ Endovascular Catheter is a device 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 and retractable radial array of conduits with multiple 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.19   
Figure 1. Bashir Endovascular Catheter 
  
 
 
Figure 2. Bashir Endovascular Catheter with Basket Expanded 
 
Table 1. Bashir™ Endovascular Catheter Dimensions 
French Size 
7 F (2.3 mm) 
Effective Length 
92.5 cm (35.44 in) 
Infusion Segment Length 
12.50 cm (4.92 in) 
 


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6.0 STUDY DESIGN 
6.1 
Study Objective 
Assess the safety and feasibility of the Bashir™ Endovascular Catheter for the 
administration of low dose thrombolysis for acute submassive pulmonary embolism. 
6.2 
Primary and Secondary Endpoints 
The primary endpoints below are appropriate for a first-in-man study. The secondary 
endpoints are for the purpose of additional safety assessments, additional procedure data 
related to any device issues (if any), and initial efficacy parameters. 
6.2.1 
Primary Endpoints 
1. Safety: Major bleeding, as defined by International Society of Thrombosis 
and Hemostasis (ISTH), within 72 hours of initiation of r-tPA 
administration.  Bleeding criteria are as follows: Major Bleeding in Non-
Surgical Patients. 
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 2g/dL (1.24mmol/L) or 
more or leading to transfusion of two or more units of whole blood or 
red cells.23 
2. Feasibility: Device success defined as the ability to use the Bashir™ 
Endovascular Catheter as per this protocol. 
6.2.2 
Secondary Endpoints 
1. All-cause mortality at hospital discharge through 30-day follow-up. 
2. SAEs through 30-day follow-up. 
3. Anticipated (non-serious) adverse events (AEs) through 30-day follow-up. 
4. Recurrent PE through 30-day follow-up.  
5. 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.  
6. Technical procedural complications. 
7. RV/LV end diastolic diameter ratio at 24 hours after completion of r-tPA 
infusion compared to baseline, by echocardiogram.  


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8. RV/LV diameter ratio at 48 hours after completion of r-tPA infusion, by 
contrast enhanced chest CTA compared to baseline. 
9. Modified Miller Index at 48 hours post r-tPA infusion as compared to 
baseline by contrast enhanced chest CTA. 
10. Systolic PA pressure measured at completion of infusion 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. 
6.3 
Eligibility Criteria 
The population to be enrolled in this study includes patients who present to the hospital 
with a submassive pulmonary embolism with symptom onset within 14 days. Patients 
18 years of age and older will be evaluated for this study and must meet all inclusion 
criteria and will have none of the exclusion criteria.  
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. 18 years of age and less than 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 contrast enhanced chest CT Scan (CTA); 
5. RV/LV diameter ratio ≥ 0.9 by contrast enhanced chest CT scan (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. Cerebrovascular Accident (CVA) or transient ischemic attack (TIA) within 
one (1) year; 
2. Head trauma, or other active intracranial or intraspinal disease within one 
(1) year; 
3. Recent (within one month) or active bleeding from a major organ;  
4. Intracranial condition(s) that may increase the risk of bleeding (e.g., 
neoplasms, arteriovenous malformations, or aneurysms); 
5. Patients with bleeding diathesis; 
6. Hematocrit < 30%; 
7. Platelets < 100,000/μL; 
8. INR > 1.5; 
9. aPTT > 50 seconds in the absence of anticoagulants;  
10. Major surgery within fourteen (14) days;  


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11. Serum creatinine > 2.0 mg/dL;  
12. Clinician deems high-risk for catastrophic bleeding;  
13. History of heparin-induced thrombocytopenia (HIT);  
14. Pregnancy; 
15. Systolic blood pressure < 90 mmHg for greater than 15 minutes;  
16. Vasopressor support; 
17. Cardiac arrest (including pulseless electrical activity and asystole) 
requiring active cardiopulmonary resuscitation (CPR);  
18. Evidence of irreversible neurological compromise;  
19. Life expectancy < one (1) year;  
20. Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days 
prior to inclusion in the study;  
21. Use of non-vitamin K oral anti-coagulants (NOACs), such as rivaroxaban, 
apixaban, dabigatran, edoxaban within 48 hours prior to inclusion in the 
study;  
22. Use of enoxaparin sodium injection (Lovenox®) within 12 hours of 
procedure start time; 
23. Profound bradycardia requiring a temporary pacemaker and/or inotropic 
support; 
24. Previous enrollment in this study;  
25. Morbidly obese (BMI >45 kg/m2) patient who by the judgement of the 
investigator is high risk for bleeding; 
26. Absolute contraindication to anticoagulation; 
27. Uncontrolled hypertension; 
28. Currently participating in another study;  
29. 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 five (5) sites will enroll a total of ten (10) subjects over 
nine (9) months. 
6.4.2 
Follow-up 
The follow-up for each subject will be completed at one (1) month post-
discharge.  
6.4.3 
Complete Study Period 
It is estimated that this study will require eleven (11) months to complete 
enrollment and follow-up. 
6.4.4 
Subject Participation 
Each subject will participate in this study for approximately 30 days from 
consent through 30-day follow-up. 


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7.0 METHODOLOGY 
7.1 
Pre-Procedure Testing Within 48 Hours Pre-Procedure 
7.1.1 
Laboratory Tests 
1. CMP, CBC, Cardiac Biomarkers Troponin I and BNP – These tests will 
be drawn within 48 hours pre-procedure. 
 
2. aPTT – Drawn within 48 hours pre-procedure. Unfractionated heparin will 
be infused to prolong the aPTT (suggested range is 60-80 seconds) prior to 
the administration of r-tPA.  The institution is to follow the standard of care 
for the administration of heparin through the completion of the r-tPA 
infusion and the monitoring of aPTT in addition to the aPTTs measured at 
certain time points required by this protocol. 
 
3. International Normalized Ratio (INR) – INR will be drawn within 48 
hours pre-procedure for patients who are on Coumadin and must be ≤ 1.5 
to be eligible for enrollment.  Patients who are on Coumadin and have an 
INR ≤ 1.5 who are in the study the coumadin will be discontinued during 
the heparin infusion and the r-tPA infusion and can be restarted prior to 
discharge.   
 
4. Fibrinogen – Fibrinogen levels are required to be checked within 48 hours 
prior to the procedure.  The assay method must be recorded (e.g. Clauss, 
PT-derived fibrinogen assay, immunological, gravimetric, other) 
7.1.2 
Imaging 
1. Contrast Enhanced CTA of Chest – A contrast enhanced CTA of chest 
will be performed within 48 hours pre-procedure.  The contrast enhanced 
chest CTA is used to determine the pre-procedure Modified Miller Index 
Score within 48 hours prior to the procedure. CT will be sent to the core lab 
for analysis. 
 
2. Lower Extremity Venous DUS – A duplex ultrasound is required 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 access may also be used if that is the operator’s 
preference. 
 
3. Echocardiogram – The echocardiogram will be done to determine the pre-
procedure RV/LV end-diastolic diameter ratio. A core lab protocol will be 
followed for data acquisition. The echocardiogram will be sent to the core 
lab for analyses.  


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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 contrast enhanced chest CTA to ensure the subject 
meets the eligibility criteria of an axial RV/LV ratio ≥ 0.9.  RV/LV ratio is 
required to be assessed by contrast enhanced chest CTA to determine 
eligibility. The site determines eligibility, and an independent core lab 
protocol will be followed for data acquisition. Both the contrast enhanced 
chest CTA and echocardiogram will be sent to the core lab for analysis. 
 
3. 12-Lead Electrocardiogram (ECG) – A 12-lead ECG will be performed 
prior to the procedure. 
7.1.4 
Anticoagulation 
Unfractionated heparin is required to be used for anticoagulation and is to be 
started pre-procedure by intravenous administration to prolong the aPTT 
(suggested range is 60-80 seconds) unless the patient has received Lovenox.  
The institution is to follow the standard of care for the administration of heparin 
and the monitoring of aPTT in addition to the aPTTs measured at certain time 
points required by this protocol. Stop the heparin administration at the 
completion of the r-tPA infusion. The final aPTT should be measured according 
to standard of care.  
7.1.5 
Patients Receiving Lovenox for Treatment of Pulmonary Embolism 
Lovenox: Use of Lovenox is permitted pre-procedure for the treatment of PE if 
it is the standard of care. If Lovenox is administered to a potential study subject, 
then catheter directed thrombolysis procedure is to start no sooner than 12 hours 
from the last Lovenox dose. 
 
During the CDT procedure in the IR suite/Cath lab ACTs will be checked and 
heparin bolus given to achieve ACT ≥ 200 seconds. 
 
After completion of the CDT procedure, a heparin drip will be started prior to 
leaving the IR suite/Cath lab to maintain therapeutic dose through completion 
of the r-tPA infusion.  
7.1.6 
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. 


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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 medications will be recorded within 48 hours pre-
procedure, at baseline. 
5. Modified Miller Index (MMI) – Modified Miller Index (MMI) will be 
calculated by the core lab at baseline. The contrast enhanced chest CTA 
will be sent to the core lab and the MMI will be calculated by the core lab 
for each contrast enhanced CTA of the chest done in this study.21  
8.0 IR SUITE/CATH LAB STUDY PROCEDURES   
Should the patients 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 of the BEC to 
expose the infusion basket. A 70 cm length sheath Flexor® Raabe Guiding 
Sheath (Cook Medical, Inc.) or equivalent for femoral access is 
recommended for most patients. A shorter sheath may be utilized for IJ 
access. 
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. guide wire lumen (Arrow® or 
equivalent) or an angled pigtail catheter.  
6. 3-way stopcock – with Luer-lock connectors. 
7. Infusion pump and IV tubing for r-tPA infusion. 
8. Heparinized saline for flushing. 
9. 0.9% NaCl intravenous (IV) infusion bag 250cc for r-tPA pulse spray 
mixture. 
10. IV infusion pump and tubing. 
11. Sterile water for injection, USP (Do not use bacteriostatic water, USP for 
injection) - for 2mg vial Cathflo Alteplase (r-tPA) mixture (Genentech, 
Inc., South San Francisco, CA). 
12. Pulse Spray r-tPA vials: 
i. Unilateral PE:  
1. One (1) 2.2mg vial of Cathflo Alteplase (r-tPA) for pulse spray use. 
2. Two (2) 10cc syringes for injecting the pulse sprays. 
ii. Bilateral PE:  


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1. Two (2) 2.2mg vials of Cathflo Alteplase (r-tPA) for pulse spray 
use. 
2. Four (4) 10cc syringes for injecting the pulse sprays. 
13. r-tPA Infusion: 
i. Unilateral PE: Obtain five (5) 2.2mg vials of Cathflo Alteplase (r-tPA) 
for continuous infusion to be started in the IR suite/Cath lab at the end 
of the procedure for a total of 10 mg for one infusion.  Mixture 
requirements are in section 9.3. 
ii. 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 at the end 
of the procedure for a total of 5 mg for each infusion for two infusions.  
Mixture requirements are in section 9.3. 
8.1.2 
Procedure Supplies Provided by the Sponsor 
1. Bashir™ Endovascular Catheter 
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). Print out 
the initial baseline readings for the PA pressures and retain with the source documentation 
in the subject binder.  Indicate where on the tracing the PAS, PAD and PA Mean are 
interpreted. 
1. PA Pressures measured using a Swan-Ganz catheter or angled pigtail:  PAS / PAD / PA 
Mean 
2. SpO2 – Arterial Oxygen Saturation (pulse oximeter O2 saturation) 
3. SvO2 - Mixed Venous Oxygen Saturations (from tip of a pigtail catheter or Swan-Ganz 
Catheter PA port) 
4. CO – Modified Fick Calculation (see terms and definitions for formula) 
5. CI – Calculation 
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™ Endovascular Catheter (BEC).   
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, with BP < 180/110 mmHg prior to PMCDT. 
2. Discontinue the peripheral IV heparin drip infusions.   
3. Obtain venous access using ultrasound guidance and Micropuncture needle. Ultrasound 
guidance and use of Micropuncture needle is mandatory for both CFV and IJ access. 
4. Place 7F sheath(s) or larger in the RCFV or access point of choice (LCFV or IJ). 
5. Check ACT - If ACT < 200 seconds, administer additional heparin bolus until ACT is 
documented to be ≥ 200 seconds. 
6. Using a .035in. exchange length wire, insert the wire into a sheath and advance it up to 
the right atrium. 


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7. Insert the Swan-Ganz or angled pigtail catheter over the wire and advance it up to the 
right atrium. 
8. Remove the guide wire. 
9. Float the Swan-Ganz catheter or angled pigtail, and record baseline hemodynamic data 
in section 8.2. 
10. Insert the exchange length STORQ™ (Cordis) guide wire, or equivalent, into the Swan-
Ganz or angled pigtail catheter.  Remove the Swan-Ganz or angled pigtail catheter. 
11. Exchange the Swan-Ganz Catheter, or angled pigtail, for a long 7F sheath (or larger) 
which is placed into the PA where the thrombus is located. 
12. Remove the guidewire and the dilator carefully from the PA making sure that the sheath 
does not jump forward. 
9.2 Bashir Endovascular Catheter Use – Procedure Steps 
1. Prepare all r-tPA solutions and IV infusion mixtures in Section 9.3 prior to opening the 
Bashir Endovascular Catheter (BEC).   
2. Prepare the BEC 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 guide wire, such as Hi-torque Steelcore 
Peripheral Guide Wire (Abbott Vascular), introduce the wire into the lumen of the long 
sheath(s) and advance up into the target pulmonary artery. 
4. Backload the BEC onto the 0.018” 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 port 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.  
7. Advance the BEC into the target PA.    
8. Do NOT aspirate back from the basket infusion port to back bleed.  Only maintain 
forward flow by infusing the r-tPA at the prescribed rate 95cc/hour for unilateral PE 
and 65cc/hour for bilateral PE, as stated in Table 2.  
9. Keeping the wire in the central wire lumen expand the infusion basket of the BEC. 
9.3 r-tPA Administration   
9.3.1 
Part 1 – r-tPA Pulse Spray - In the IR suite/Cath lab through the BEC 
1. Reconstitution of r-tPA Pulse Spray Mixture  
a. Obtain a 2.2mg vial of r-tPA (1mg/ml) provided by study site. 


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b. Mix the lyophilized powdered r-tPA with 2.2ml sterile water for 
injection provided by study site (as stated in the r-tPA information 
sheet) to obtain 1mg/ml. Do not use bacteriostatic sterile water for 
injection. 
c. Aspirate exactly 1mg (1ml) into a 3cc syringe (for accuracy)  
d. Inject 1mg (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.   
e. Repeat (c) and (d) above x 1. 
f. This equals two (2) 10cc pulse spray doses (1mg/10cc in one 10cc 
syringes per pulse spray) with 1mg r-tPA per dose -Total of 2 mgs of 
r-tPA for unilateral PE). 
g. If treating bilateral PE, repeat steps (c) through (f) above. 
Table 2. r-tPA Doses and Mixtures for Pulse Sprays and Infusions through the BEC Provided by Site 
Pulse Sprays 
Infusion 
 
No. of 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 
Number of 
2mg 
Cathflo™ 
r-tPA 
Vials 
Required 
Amount of 
Diluent 
Required 
 
0.9% NaCl 
Infusion 
Rate 
Unilateral 
PE 
1 
2.2 ml per 
vial to 
have 
1mg/ml 
Total of 
20cc 
including 
r-tPA  
2 mg in 
20 cc 
divided 
into 2 
10cc 
syringes 
2 pulse 
sprays in 
two 10cc 
syringes = 
two 10cc 
syringes  
5 
(10mg x 1 
infusion) 
750cc total 
including 
r-tPA 
mixture x 1 
bag 
95cc/hr= 
1.27mg/hr 
x 1 infusion 
until 
complete 
10mg total 
Bilateral 
PE 
2 
4.4 ml in 
2 vials for 
1mg/ml 
Total of 
40cc 
including 
r-tPA  
2 mg in 
20cc x 2, 
divided 
into four 
10cc 
syringes 
2 pulse 
sprays in 
two 10cc 
syringes = 
four 10cc 
syringes 
5 
(5mg x 2 
infusions) 
500cc total 
including 
r-tPA 
mixture x 2 
bags 
65cc/hr= 
.65mg/hr per 
infusion x 2 
infusions 
until 
complete 
10mg total 
2. Reconstitution of r-tPA IV Infusion Mixture 
a. Unilateral PE 
i. Obtain a 1,000cc bag of 0.9% NaCl for infusion. 
ii. Aspirate 250cc of 0.9% NaCl from the 1,000cc IV bag to have a 
total diluent of 750cc. 
iii. Mix five (5) vials (2.2 ml injected into 2.2 mg vials) of r-tPA with 
sterile water for injection until the lyophilized powder is dissolved, 
for a total of 10 mg of r-tPA.   
iv. Aspirate 10ml (10mg) into a syringe. 
v. Verify 10ml are aspirated in the syringe. 


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vi. With a new syringe aspirate the amount of fluid from the IV bag 
that is equal in amount to the r-tPA solution in the r-tPA syringe, 
10ml, so the total volume in the bag with the r-tPA will be 750cc.   
vii. Inject the 10 mg solution of r-tPA into the IV bag for infusion.  You 
should have a total of 10mg of r-tPA in a total of 750cc of diluent. 
viii. Set aside for use at the end of the pulse spray procedure(s). 
b. Bilateral PE 
i. Obtain two (2) 500cc bags of 0.9% NaCl for infusion. 
ii. Mix five (5) 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).   
iii. Aspirate 10ml (10mg) dose into a syringe. 
iv. Verify 10ml are aspirated into the syringe. 
v. Determine the total number of mls in the syringe and note 5ml is 
one-half of the volume of the solution for one-half of the dose. 
vi. With a new syringe aspirate the amount of fluid from the IV bag 
that is equal in amount to one-half of the r-tPA solution in the r-
tPA syringe, 5ml, so the total volume in the bag with the r-tPA will 
be 500cc once the 5mg of r-tPA is added to the IV bag. Repeat for 
second IV bag.   
vii. Inject 5mg (5ml) solution of r-tPA into one (1) IV bag for infusion.  
Inject the second 5mg solution of r-tPA into the second IV bag for 
infusion.  You should have a total of 5mg of r-tPA in a total of 
500cc of diluent in each IV bag for bilateral PE, a total of 10mg 
split among the two IV bags. 
viii. Set aside for use at the end of the pulse spray procedure(s). 
 
3. Pulse Spray of r-tPA for Unilateral and Bilateral PE 
a. Unilateral PE:  With the catheter in the target PA, and after verification 
the basket portion of the catheter has exited the sheath under 
fluoroscopy, and 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. Attach the pulse spray syringe to the unused port of the stopcock 
attached to the basket infusion port. Pause the infusion pump of the r-
tPA infusion. Turn the stopcock so that it is closed to the infusion pump 
line and open to the syringe and to the basket infusion port. 
c. Administer 10cc (1mg 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.  
d. Under fluoroscopy, and guidewire in place, collapse the basket and re-
expand the basket. 
e. Repeat this with the second 10cc syringe (1mg r-tPA in 10ml) over 10-
15 seconds. 


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f. As soon as the pulse sprays are administered, immediately re-start the 
r-tPA infusion via the basket infusion port of the BEC. 
g. Bilateral PE: Repeat steps a-f in contralateral pulmonary artery for 
bilateral PE. 
h. Once pulse sprays are complete, the basket(s) should remain expanded. 
i. 
As soon as the pulse sprays are administered, immediately re-start the 
r-tPA infusion via the basket infusion port of the BEC in accordance 
with Table 2. Refer to Section 9.3.2 and Table 2 for r-tPA infusion 
instructions.   
j. 
Remove the guidewire(s) from the wire lumen(s). 
k. Ensure the BEC(s) are adequately flushed.  Attach the flushed pressure 
transducer tubing to the wire lumen of the BEC(s).  Measure the 
systolic PA, diastolic PA, and mean PA pressures in each PA with a 
pulmonary embolism from the tip of the BEC through the guidewire 
lumen at the back of the BEC handle. Print the PA waveform tracings 
and mark the tracings where the systolic PA, diastolic PA, and mean 
PA pressures are interpreted and documented.  
l. 
If the waveform is dampened, adequately flush the wire lumen.  If the 
waveform is still dampened after it is flushed, print the dampened 
waveform on paper, and retain the waveform with the source 
documentation for this study. Measure the systolic PA, diastolic PA, 
and mean PA pressures in each PA with a pulmonary embolism on the 
tracing.  If the waveform becomes phasic prior to leaving the lab, print 
the waveform, mark on the waveform where the systolic PA, diastolic 
PA, and mean PA pressures are interpreted and the time the waveform 
became phasic. Retain the printout with the source documentation for 
this study.  
9.3.2 
Part 2 – r-tPA Infusion and Anticoagulation – Prior to Departing the IR 
suite/Cath lab r-tPA Infusion 
Upon completion of the Pulse Sprays, with the basket re-expanded and catheter 
securely in place, begin r-tPA solution infusion(s), as soon as possible 
(immediately following the pulse sprays).   
1. For unilateral PE: The total r-tPA is 10mg at 1.27mg/hr. Using an IV 
pump at 95cc/hour, infuse the 750cc of 0.9% NaCl with the 10mg r-tPA at 
1.27mg/hr until infusion is complete (approximately 8 hours). 
2. For bilateral PE: The total r-tPA dose is 10mg at 1.30mg/hr. Using two 
(2) IV pumps at 65cc/hour, infuse the 500cc of 0.9% NaCl x 2 
simultaneously with the 5mg r-tPA at 0.65mg/hr for each PE for a total of 
1.3mg/hour until complete (approximately 8 hours).  
3. Anticoagulation: Re-start low dose heparin infusion into each sheath to 
prolong the aPTT (suggested range 40 to 60 seconds) prior to leaving the 


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IR suite/Cath lab to maintain therapeutic dose through completion of the 
48-hour CT scan. 
 
The institution is to follow the standard of care for the administration of 
heparin and the monitoring of aPTT in addition to the aPTTs measured at 
certain time points required by this protocol. 
4. Maintaining Patency Through the Central Lumen of the BEC(s): 
Remove the wire from the central lumen of the BEC and attach a 3-way 
stopcock and flush with heparinized saline to maintain patency in the 
central lumen of the BEC (both BECs if bilateral PEs) when transferring to 
ICU.  
 
If it is standard of care in the IR suite/Cath lab to attach pressure tubing 
prior to transfer to the ICU for continuous PA pressure monitoring in the 
ICU, that may be done in lieu of heparinized flush in a syringe to maintain 
patency when transferring from the IR suite/Cath lab to the ICU.  The 
central lumen of the BEC will be used for continuous monitoring of the PA 
pressures in the ICU.  Hospital standard protocol will be used to maintain 
patency of the central lumen and to perform continuous pressure 
monitoring through the BEC in the ICU.  
 
For example, heparinized saline to a pressure bag and pressure monitor 
tubing connected to the bedside monitor to transduce pressure from the 
central lumen of the BEC may be performed; if there are two BECs in place 
for bilateral PEs, the central lumen of both BECs require pressure tubing 
for continuous pressure monitoring and kept open with standard pressure 
tubing transduced to the bedside monitor using heparinized saline in a 
pressure bag to keep the line patent and for continuous PA pressure 
monitoring and SvO2 draws. 
9.4 Intra-procedure Data Collection Requirements 
1. Hemodynamic readings 
2. ACT 
3. AEs / SAEs 
4. Times of pulse sprays administration 
5. Time the r-tPA infusion(s) started 
6. Time of heparin infusion(s) started 
7. Technical complications 
8. Medications 
9. Equipment used 
10. Blood pressure and heart rate, at start of procedure 
9.5 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. Attach a 3-way stopcock and tubing to maintain patency and for continuous 
monitoring of the PA pressures in the ICU and an IV to keep open (TKO) 


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the central lumen (wire lumen) of the catheter per hospital standard protocol 
for each BEC.  
4. Securing the device(s):   
a. For CFV Access: tape device to thigh.  Then follow step “e” below. 
b. For 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. 
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. 
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 eight (8) 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. 
a. Unilateral PE: Infusion rate is to be maintained at 95cc/hour through the BEC, for 
a total of 1.27mg/hour infusing into the patient over approximately eight (8) hours.  
(95cc/hr= 1.27mg/hour x 1 infusion x approximately 8 hours = 10mg total). Infuse 
the r-tPA mixture until the infusion is complete.  
b. Bilateral PE: Infusion rate is to be maintained at 0.65mg/hour through each 
catheter, for a total of 1.3mg/hour infusing into the patient (0.65mg/hour through 
each BEC).  This is a rate of 65cc/hour per infusion for a total of 130cc/hour total 
infusing through two catheters into the patient. Infuse the r-tPA mixture until the 
infusion is complete  
2. Laboratory Tests: Four (4) hours (±1 hour) after initiation of heparin infusion started 
in the IR suite/Cath lab measure: 
a. CBC 
b. aPTT 
3. Hemodynamic Readings: Record the following pressures in the ICU beginning with 
the 1st reading two (2) hours (±30 minutes) after the initiation of the r-tPA infusion and 
then every thirty (30) minutes (±15 minutes) thereafter through the central lumen of the 
BEC.  If a waveform, or both waveforms (if bilateral) appear dampened, verify each 
BEC pressure transducer is set up properly when study subject arrives in ICU.  If the 
waveform continues to be dampened, document the date and time when the waveform 
becomes phasic and print the waveform from the monitor.  Mark on the waveform where 
the systolic PA, diastolic PA, and mean PA pressures are read and retain with the source 
documentation for this study.  Please note that when the waveform becomes phasic, it 
must be documented even if it outside of the “every 30 minutes” scheduled readings. 
This is so the length of time from the 1st pulse spray (in the Cath/IR lab) to when the 


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clot dissolves in each PA with a pulmonary embolism will be known.   Please note that 
printouts are not required for every reading, only when the dampened waveform 
becomes phasic, if dampened when subject arrives in the ICU. These readings are 
required through the completion of r-tPA infusion: 
a. PAS / PAD / PA Mean Pressures  
b. SpO2 – Arterial Oxygen Saturation (pulse oximeter O2 saturation)  
4. Mixed Venous Oxygen Saturation (SvO2): Record every two (2) hours (±30 minutes) 
in the ICU starting after the initiation of the r-tPA infusion. These readings are required 
through the completion of r-tPA infusion: 
a. SvO2 – Mixed Venous Oxygen Saturations (Sample is from tip of the BEC, 
drawn from the central lumen of the BEC at the end of the handle. If bilateral, 
either BEC is acceptable for drawing the SvO2.) 
5. Anticoagulation – Intensive Care Unit During r-tPA Infusion: Heparin drip should 
be administered until the r-tPA infusion is complete (approximately 8 hours).  
6. Anti-coagulation Immediately Post-rtPA Infusion:  Once the r-tPA infusion is 
complete, turn off the heparin gtt. Starting 45 minutes (±15 minutes) after the r-tPA 
completion, administer Lovenox 1mg/kg sub-Q every 12 hours (±30 minutes) through 
the completion of the 48-hour CTA. 
7. Physical Exam: A physical exam is required to be performed at the completion of the 
r-tPA infusion.  
8. Stopping r-tPA Infusion in ICU at the End of 8 Hours:  Upon completion of r-tPA 
infusion, maintain patency through the BEC by replacing r-tPA with heparinized saline 
using the infusion pump, at TKO, and transport to IR suite/Cath lab to remove BEC. 
Heparinized saline should infuse via infusion pump through the basket infusion port 
until subject arrives at the IR suite/Cath lab for catheter removal. 
10.2 Return to The IR suite/Cath lab at The Completion of Infusion 
At the end of the infusion the patient returns to the IR suite/Cath lab within eight (8) hours 
(+8 hours) of the completion of the r-tPA infusion for removal of the BEC(s) and final 
hemodynamic measurements.  
 
1. Under fluoroscopy, collapse the basket(s) of the BEC. 
2. Remove the BEC by pulling the catheter(s) carefully into the sheath(s) and then 
removing them from the body. 
3. Back bleed or aspirate the sheath(s) and flush with heparinized saline to prevent clot 
formation. 
4. Catheter for Hemodynamic Readings and Blood Draws:   Insert a Swan-Ganz or 
angled pigtail catheter through the sheath and record the following. 
 
a. Hemodynamic Readings 
i. SvO2 – Mixed Venous Oxygen Saturations  
ii. SpO2 – Arterial Oxygen Saturation (pulse oximeter) 
iii. PA Pressures:  PAS / PAD / PA Mean 


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iv. CO – Modified Fick calculation (Refer to Terms and Definitions for 
required calculation) 
v. CI – Calculation  
b. Fibrinogen – To be drawn at the time of the device removal in the IR suite/Cath 
lab.  The assay method must be recorded (e.g. Clauss, PT-derived fibrinogen 
assay, immunological, gravimetric, other) 
10.3  Tests Required at End of Infusion(s) and 24 Hours After r-tPA Infusion  
10.3.1 Laboratory Tests and Other Tests 
1. BMP, CBC, Cardiac Biomarkers Troponin I and BNP – These tests will 
be drawn 24 hours (±8 hours) after completion of the r-tPA infusion. 
 
2. aPTT – To be drawn once heparin gtt is stopped according to standard of 
care and ONLY IF it is standard of care to check aPTT after heparin gtt is 
discontinued.    
10.3.2 Imaging 
1. Echocardiogram – The echocardiogram will be done to determine the 
RV/LV end-diastolic diameter ratio at 24 hours (±8 hours) from the 
completion of the r-tPA infusion.  A core lab protocol will be followed for 
data acquisition. The echocardiogram will be sent to the core lab for 
analyses. 
10.3.3 Assessments 
1. Physical Examination – The physician will perform a physical 
examination at the end of the infusion and 24 hours (±8 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. 
10.3.4 Data Collection 
The following data will be collected and documented in the CRF in 
addition to the required pre-procedure testing. 
1. Medications – All medications 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. 
3. RV/LV End Diastolic Diameter Ratio – This will be measured and 
calculated by echocardiogram at 24 hours (±8 hours) following completion 
of the r-tPA infusion. The imaging will be sent to the independent core lab 
for analysis. 


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10.4 Tests Required 48 Hours Following End of r-tPA Infusion  
10.4.1 Imaging 
1. Contrast Enhanced CTA of the Chest – A contrast enhanced chest CTA 
will be performed at 48 hours (±6 hours) after completion of the r-tPA 
infusion.  The contrast enhanced chest CTA is used to determine the post-
procedure RV/LV diameter ratio and Modified Miller Index Score. Please 
note that subject must be on Lovenox 1mg/kg every 12 hours through the 
completion of the 48-hour CTA. The CT will be sent to the core lab for 
analyses. 
10.4.2 Assessments 
1. AE/SAEs – Adverse events will be monitored and reported on the CRF 
post-procedure through 48 hours. 
10.4.3 Data Collection 
1. Medications – All medications will be recorded that are administered 
within 48 hours following the infusion completion. 
2. RV/LV End Diastolic Diameter Ratio – This will be measured and 
calculated by CTA at 48 hours (±6 hours) following completion of the r-
tPA infusion. The imaging will be sent to the independent core lab for 
analysis. 
3. Modified Miller Index Score – This will be documented by the core lab 
after the contrast-enhanced chest CTA is performed. This will also be 
performed by the independent core lab. 
10.5 Anticoagulation and Sheath Removal 
10.5.1 Lovenox Administration 
The subject must continue Lovenox 1mg/kg administered sub-Q every 12 hours (±30 
minutes) through the completion of the 48-hour CTA.   
10.5.2 FDA Approved Anticoagulation Regimen  
At the time of r-tPA infusion completion and through the completion of the 48-hour CTA, 
administer Lovenox 1mg/kg subcutaneously.  Study subjects may be prescribed any FDA 
approved regimen of anticoagulation after the 48-hour CTA scan is complete. The long-
term anticoagulation administration is according to the physician’s discretion. 
10.5.3 Sheath Removal   
The sheath removal date and time will be determined by the treating investigator and the 
study subject’s condition and coagulation status.  The sheath(s) shall be removed as soon 
as possible after removal of the BEC. Before removal, the sheath should be carefully 
aspirated then flushed to eliminate any clots. 


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10.6 Tests Required 72 Hours (+12 hours) Following Start of r-tPA Administration 
10.6.1 Assessments 
1. AE/SAEs – Adverse events will be monitored and reported on the CRF 
post-procedure through discharge. Bleeding complications will be 
assessed through 72 hours (-4 / +12 Hours) following initial 
administration of the first r-tPA dose that was administered in the IR 
suite/Cath lab.   
10.6.2 Data Collection 
1. Medications – All medications will be recorded that are administered 
within 72 hours following the infusion.  
10.7 Tests Required Just Prior to Hospital Discharge 
10.7.1 Assessments 
1. Physical Examination – The physician will perform a physical 
examination within eight (8) hours (-8 Hours) of discharge.   
2. AE/SAEs – Adverse events will be monitored and reported on the CRF 
post-procedure through discharge. 
3. 12-Lead Electrocardiogram – To be done prior to and no greater than 
within eight (8) hours (-8 Hours) prior to discharge. 
11.0 
30-DAY FOLLOW-UP VISIT POST PROCEDURE 
11.1 
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.    
 
  
11.2 
Data Collection 
1. 
Medications – All medications since discharge will be recorded at 30-day follow-up. 
12.0 
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 associated with the use of a 
drug in humans, whether or not considered drug related (21 CFR 312.32(a)). 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug caused the adverse event. For the purposes of IND safety reporting, ‘reasonable 
possibility’ means there is evidence to suggest a causal relationship between the drug and the 
adverse event. A suspected adverse reaction implies a lesser degree of certainty about causality 
than adverse reaction, which means any adverse event caused by a drug. A suspected adverse 
reaction is an adverse event where there is a reasonable possibility the drug caused the adverse 
event. The sponsor is responsible for making the causality. 


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12.1 
Bashir Endovascular Catheter Anticipated Adverse Events  
Table 3. Anticipated Adverse Events Related to the Investigational Device18 
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 
12.2 
r-tPA Anticipated Adverse Events 
Table 4.  Anticipated Adverse Events Related to r-tPA Infusion15 
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 blood vessel  
Thromboembolism 
Obstruction of a blood vessel by a clot that has become dislodged 
 
 
12.3 
Anticipated Adverse Events Related to the Procedure 
Table 5. Anticipated Adverse Events Related to the Procedure20 
Adverse Event 
Definition 


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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 
 
13.0 
ADVERSE EVENT REPORTING 
13.1 
Serious Adverse Events and Serious Suspected Adverse Reactions 
Serious adverse events (SAE) or serious suspected adverse reaction (SUSAR) 
must be reported to the study manager within 24 hours of knowledge of the 
event.   
Serious adverse event or serious suspected adverse reaction:   An adverse event or 
suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes:  
1. Death;  
2. A life-threatening adverse event; 
3. Inpatient hospitalization or prolongation of existing hospitalization; 
4. A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, or a congenital anomaly/birth defect;  


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5. Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition.   
The following event definitions, as defined in 21 CFR 312.32(a) will be reported 
as serious adverse events and the reporting requirements above must be 
followed.  
Life-threatening 
adverse 
event (or life-threatening 
suspected 
adverse 
reaction):  An adverse event or suspected adverse reaction is considered "life-
threatening" if, in the view of either the investigator or sponsor, its occurrence places 
the patient or subject at immediate risk of death. It does not include an adverse event or 
suspected adverse reaction that, had it occurred in a more severe form, might have 
caused death. 
13.2 
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction 
The following event definitions, as defined in 21 CFR 312.32(a) will be reported 
as serious adverse events and the reporting requirements above must be 
followed.  
An Adverse Event or Suspected Adverse Reaction is considered "unexpected" if it is 
not listed in the investigator brochure or is not listed at the specificity or severity that 
has been observed; or, if an investigator brochure is not required or available, is not 
consistent with the risk information described in the general investigational plan or 
elsewhere in the current application, as amended.  
It is anticipated that no unexpected adverse reactions will occur as r-tPA is FDA 
approved for the treatment of pulmonary embolism.  The currently approved 
labeling requires 100mg of r-tPA to be administered intravenously over two (2) 
hours. This is 86mg more than the maximum dose required in this protocol 
administered over two (2) hours, not over approximately eight (8) hours as in 
this protocol. 
13.3 
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. 
 
13.4 
Adverse Event Relatedness 
Table 6. Adverse Event Categories of Device Relatedness 
Relatedness 
Term 
Relatedness Definition 


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Related 
The adverse event is clearly related to the investigational 
agent/procedure – i.e. an event that follows a reasonable 
temporal sequence from administration of the study intervention, 
follows a known or expected response pattern to the suspected 
intervention, that is confirmed by improvement on stopping and 
reappearance of the event on repeated exposure and that could 
not be reasonably explained by the known characteristics of the 
subject’s clinical state. 
Possibly 
Related 
An adverse event that follows a reasonable temporal sequence 
from administration of the study intervention follows a known or 
expected response pattern to the suspected intervention, but that 
could readily have been produced by a number of other factors. 
Not Related 
The adverse event is clearly not related to the investigational 
agent/procedure - i.e. another cause of the event is most 
plausible; and/or a clinically plausible temporal sequence is 
inconsistent with the onset of the event and the study intervention 
and/or a causal relationship is considered biologically 
implausible. 
13.5  
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 patients’ 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. Patients 
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.  
14.0 
REGULATORY REQUIREMENTS 
The following are requirements of the sponsor and of the investigators.  


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14.1 
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 CFR part 50. [21 CFR 312 Subpart D]. 
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 subpart G. 
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. The r-tPA, sterile water, and 0.9% NaCl for infusion 
will be provided by the site. Detailed documentation of the dosage and 
administration of the drug will be performed by the site for each study subject. 
Disposition of each study device will be documented by the site.   
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. Form 1572 will be completed and signed by the investigator prior to commencement 
of the study. 
7. 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. 
8. 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: 


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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. 
9. 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. 
10. The protocol, with documents showing the dates of and reasons for each deviation 
from the protocol. 
11. Any other records that FDA requires to be maintained by regulation or by specific 
requirement for a category of investigations or a particular investigation. 
12. 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 
13. 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 and Echocardiograms: 
Medical Metrics, Inc. 
2121 Sage Road 
Suite 300 
Houston, TX 77056 
14. 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 


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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).  
14.2 
Sponsor Responsibilities 
1. General Duties 
a. Submitting the IND 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 
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 312, 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. Investigator Brochure 
c. Case Report Form 
d. Informed Consent 
e. FDA Letter to Commence the Study 


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4. Refer to Section for Section 18 for Safety Reporting Requirements 
14.3 
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. 
15.0 
DEVICE AND DRUG ACCOUNTABILITY 
15.1 
Bashir™ Endovascular Catheter Packaging for the IR suite/Cath lab 
The Bashir™ Cather is packaged to provide protection during transportation and to 
facilitate introduction into the sterile environment.  The shaft of the Bashir Catheter 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. 
15.2 
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. 
15.3 
Drug Accountability 
The sites shall provide Cathflo® Activase (Alteplase) (r-tPA) and sterile water from their 
respective pharmacy for use in this study.   The site will document each vial and drug 
disposition on the drug accountability log provided to the site.  
16.0 
STATISTICAL CONSIDERATIONS 
16.1 
Sample Size Justification 
The sample size selected (10) is considered to be a number sufficient to gather essential 
early information on the safety and performance of the device. The essential information 
is identified in the primary and secondary endpoints defined. The sample size will also 
assist in identifying additional meaningful data points, refine study endpoints, and 
improve study procedures before proceeding to a larger statistically powered pivotal 
trial. 


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16.2 
Data Analysis 
Data collected will be summarized using descriptive statistics. The study is not 
statistically powered for the analysis of primary endpoints.   Concomitant medications 
will be coded using the World Health Organization (WHO)-drug dictionary and AEs 
will be coded using the Medical Dictionary for Regulatory Affairs (MedDRA). 
16.3 
Data Entry 
 
Data will be entered into a 21 CFR 11 compliant database, electronic data capture 
(EDC) for this study.  The site staff shall be responsible for data entry. 
17.0 
DATA SAFETY MONITOR 
A data safety monitor will be selected to review the study conduct, feasibility data, and safety data and 
will adjudicate all types of adverse events reported in this study.  The independent DSM shall have the 
final adjudication for the events.  A data safety charter will be established and will be approved by the 
data safety monitor.  Qualifications for the DSM, at a minimum, shall include current experience with 
catheter directed thrombolysis for the treatment of massive and 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 DSM meetings in addition to following the 
charter. 
18.0 
STUDY STOPPING CRITERIA 
This first-in-man study is to demonstrate safety and device success defined as the ability to use the 
Bashir™ Endovascular Catheter as intended for the treatment of pulmonary embolism.  The treatment 
for pulmonary embolism in this study utilizes the Bashir™ Endovascular Catheter for the delivery of r-
tPA into the pulmonary artery. The dose of r-tPA in this study is much less than the FDA approved 
prescribed dose (FDA approved dosing 100mg infused intravenously over two hours for massive PE 
versus this study dose of approximately 12mg [for unilateral PE] to approximately 14mg [for bilateral 
PEs] over approximately 8 hours into the PA).   The study stopping criteria will be based on criteria 
related to bleeding, device use, and early efficacy. 
 
18.1 
General Study Stopping Rules 
18.1.1 The Sponsor, DSM, 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.  
18.1.2 If the study is terminated or suspended, prompt notification will be provided to 
all parties involved in the conduct of the study. 
18.1.3 Patient enrollment may be paused or terminated early if the Sponsor or DSM 
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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18.2 
Safety Study Stopping Rule 
If two (2) patients undergoing the investigational procedure die or experience 
an unprovoked intracranial hemorrhage, confirmed by independent DSM 
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.  
18.3 
Efficacy Study Stopping Rule 
Should the treatment not achieve a reduction in RV:LV ratio as measured by 
CT at 48 hours by at least 0.06 compared to baseline, in three of the first three 
patients, the study shall be paused for re-evaluation. 
18.4 
Device Study Stopping Rules 
18.4.1 Should it be suspected that a device caused a serious adverse event, the serious 
adverse event will be adjudicated by the independent DSM and the device shall 
be returned to the manufacturer.  A root cause analysis shall be performed. The 
DSM will determine if the study should be stopped, temporarily suspended, or 
continued after each such event.   
 
18.4.2 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 three (3) 
patients from being treated in this study, the study shall be paused for re-
evaluation.   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.   
18.5 
Study Safety Reporting Requirements 
The following reporting requirements are the responsibility of the sponsor and are 
transferred to Eminence Clinical research, Inc. to meet these reporting obligations.  For 
investigations of marketed drugs under an IND, such as in this study requiring the 
administration of FDA approved r-tPA, Eminence Clinical Research, Inc. shall submit 
IND safety reports for suspected adverse reactions that are observed in the clinical study 
at study sites (21 CFR 312.32).   
Diane Horwitz, PhD 
Eminence Clinical Research, Inc. 
Principal Regulatory Consultant 
dhorwitz@ecr-inc.com 
Phone: (703) 307-2921 
 
 


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19.0 
VERSION CONTROL 
Add to table below for each protocol amendment 
PROTOCOL THRO-CLIN-2018-01 
VERSION 
SUMMARY OF THE CHANGE 
RATIONALE 
0.0 
Original for FDA Review 
N/A 
1.0 
Efficacy study stopping rule added 
Response to FDA 
Clinical Hold Letter 
2.0 
Efficacy study stopping rule wording clarified; 
Core Lab Contact Updated; Supplier of 
CathFlo® Activase changed from Sponsor to 
Site; Typographical errors corrected 
Respond to FDA 
request; make 
additional 
corrections 
3.0 
r-tPA Infusion calculation correction; 
elimination of “end diastolic” referenced with 
CTA; Modify anticoagulation protocol for 
patients on Lovenox 
Additional 
corrections and 
clarifications 
4.0 
Change BMI exclusion to >45; clarify heparin 
infusion duration; specify use of 7Fr sheath of 
appropriate length; add instruction to maintain 
patency of BEC with infusion pump after r-tPA 
infusion; re-order procedure steps for heparin 
bolus after obtaining access; Change 24 and 48 
hour assessments start point from “start of r-
tPA administration” to “end of r-tPA infusion” 
Additional 
corrections and 
clarifications 
5.0 
Remove heparin infusion following completion 
of r-tPA infusion; administer Lovenox for anti-
coagulation at completion of r-tPA through the 
completion of the 48-hour CTA. Continue anti-
coagulation according to standard of care after 
the CTA is complete.  
Edit protocol with 
recommendations 
from the sponsor’s 
Scientific Advisory 
Board 
6.0 
Change time of commencing r-tPA infusion in 
the IR Suite / Cath Lab and specify the window 
of time permitted for Lovenox to be started and 
then administered every 12 hours.    
Prevent blood from 
clotting in the 
infusion limbs of the 
basket. Window 
added for 
clarification. 
 
 
 


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20.0 
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7. Aggarwal V, Nicolais C, Lee A, Bashir R. et al. Acute management of pulmonary 
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8. Zarghouni M, Charles H, Maldonado T et al. Catheter-directed interventions for 
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10. Jaff M, McMurtry S, Archer S et al. Management of massive and submassive pulmonary 
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11. Daley MJ, Murthy MS, and Peterson EJ.  Bleeding risk with systemic thrombolytic 
therapy for pulmonary embolism: scope of the problem. Therapeutic Advances in Drug 
Safety; 2015;6(2):57-66. 
12. Jarrett H, Bashir R. Interventional management of venous thromboembolism: state of the 
art. Amer J of Roentgenol 2017; 208(4):1-8 
13. Enden T, Wik H, Kvam A et al. Health-related quality of life after catheter-directed 
thrombolysis for deep vein thrombosis: secondary outcomes fo the randomized, non-
blinded, parallel-group CaVenT study. Brit Med J Open 2013:3:1-8 
14. Søgaard K, Schmidt M, Pedersen L et al. 30-year mortality after venous 
thromboembolism: a populated-based cohort study. Circulation. 2014;130:829-36. 
15. Ferrigno L, Bloch R, Threlkeld et al. Management of pulmonary embolism with rheolytic 
thrombectomy. Can Respir J, Vol 18(4):e52-e58 
16. Activase_prescribing package, 2017 Revision. 
17. Piazza G, Hohlfelder B, Jaff M et al. A prospective, single-arm, multicenter trial of 
ultrasound-facilitated, catheter-directed, low-dose fibrinolysis for acute massive and 
submassive pulmonary embolism-SEATTLE II Study. J Am Coll Cardiol Interv. 
2015;8:1382–92. 


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part without written permission from Thrombolex, Inc. 
18. Sterling KM.  Late-breaking Trial Results: Long-term Results of the OPTALYSE PE 
Trial. Oral Presentation: International Society of Endovascular Therapy, January 2018. 
19. Bashir™ Endovascular Catheter Instructions for Use, 2017 Thrombolex, Inc. 
20. Evans DC, Doraiswamy VA, Prosciak MP et al. Complications of pulmonary artery 
catheters: A comprehensive critical review.2009;98:199-208. 
21. http://www.calculator.net/body-surface-area-calculator.html accessed online January 28, 
2018. Archives of Internal Medicine 17 (6): 863-71.    
22. 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 Radiol, 2001;176:1415-20. 
23. Schulman S, Angeras U, Bergqvist D et al. Definition of major bleeding in clinical 
investigations of antihemostatic medicinal products in surgical patients. Journal of 
Thrombosis and Haemostasis, 2009;8:202-04. 
 


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21.0 APPENDICES 
 
 


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Thrombolex, Inc. 
APPENDIX 21.1  
REQUIRED STUDY PROCEDURES 
Test 
Pre- 
Procedure Procedure
Post- 
Procedure 
End of  
Infusion 
24 Hrs 
Post-r-tPA 
Completion 
48 Hrs  
Post-r-tPA 
Completion 
72 Hrs  
Post- r-tPA 
Initiated 
Before 
Dis- 
charge 
30-day 
Follow-
up 
Visit Window 
≤ 48 Hrs of 
procedure 
 
 
+8  
Hrs 
±8  
Hrs 
±6 
Hrs 
-4 / +12 
Hrs 
-8  
Hrs  
±7  
Days 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Demographics and Medical History  
X 
 
 
 
 
 
 
 
 
Physical Examination 
X 
 
 
X 
X 
 
 
X 
X 
12 Lead ECG 
X 
 
 
 
 
 
 
X 
 
CBC, INR1 
X 
    
 X2 
 
X 
 
 
 
 
aPTT 
 X2 
    
X 
X 
 
 
 
 
 
Fibrinogen3 
X 
 
 
X 
 
 
 
 
 
CMP 
X 
 
 
 
 
 
 
 
 
BMP 
 
 
 
 
X 
 
 
 
 
Cardiac Biomarkers: Troponin I, 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 
 
 
 
Echocardiogram 
X 
 
 
  
X 
 
 
 
 
RV/LV Diameter Ratio with each Echocardiogram 
X 
 
 
 
X 
 
 
 
 
Eligibility Criteria 
X 
X 
 
 
 
 
 
 
 
Anticoagulation3  (Heparin, Lovenox) 
X 
X 
X 
X 
X 
X 
 
 
 
IR / Cath Lab: Invasive Hemodynamic Data / ACT4 
 
X 
 
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 q 30 Min via BEC 
 
 
X 
X 
 
 
 
 
 
ICU:  Mixed venous SvO2 q2 Hours via BEC 
 
 
X 
X 
 
 
 
 
 
r-tPA Infusion  
 
X 
X 
 
 
 
 
 
 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs / SAEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
Contrast Enhanced CTs to Core Lab 
X 
 
 
 
 
X 
 
 
 
Echocardiograms to Core Lab 
X 
 
 
 
X 
 
 
 
 
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 60-80s.  Suggested aPTT during r-tPA administration is 40-60s. Check aPTT and CBC 4 hr (±1 hr) after heparin is restarted in the IR suite/Cath lab (suggested range 60-80s). 
3 Unfractionated Heparin will be infused IV pre-procedure or Lovenox. Stop Heparin prior to start of procedure. Restart Heparin post procedure with r-tPA infusion. Fibrinogen to be drawn at time of BEC removal in IR suite/Cath lab. 
 Heparin infusion will continue until the completion of the r-tPA infusion. Lovenox 1mg/kg Sub-Q will be started 45 minutes (±15 minutes) from the completion of the r-tPA infusion and given q12hrs (±30 min). 
4Required: PAS, PAD, PA Mean, CO, CI, SpO2, SvO2 / ACT - in IR/Cath lab at baseline (print waveforms) and post-infusion in the IR suite/Cath Lab. Swan-Ganz or angled pigtail may be used. CO= Modified Fick calculation. ACT 
will be done to achieve  (and document) an ACT ≥ 200 seconds.  
5IV 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 at the rate prescribed in this protocol, which is a duration of approximately 8 
 hours. Once the r-tPA infusion is complete, heparinized saline must infuse TKO using the infusion pump until BEC removal.


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without written permission from Thrombolex, Inc. 
APPENDIX 21.2 
STUDY SCHEMA 
 
Informed Consent 
CBC, aPTT, Fibrinogen, 
CMP, (INR if on Coumadin),  
Cardiac biomarkers: Troponin I and BNP 
Echo, Contrast Enhanced  
Chest CTA, ECG 
Physical Exam Demographics & 
History Data 
Determine Eligibility 
Dx:  Submassive PE 
DUS to evaluate access site if free 
of DVT (Can also be done in Lab) 
IR/Cath Lab 
Stop Heparin GTT(s) 
Verify Labs, Start Heparin GTT to 
prolong the aPTT  
(Suggested levels 60-80 seconds). 
Attach r-tPA Infusion and flush Basket Infusion Port(s) then Insert BEC Catheter(s) 
r-tPA Pulse Sprays 
r-tPA Infusion(s) 
Remove guidewire(s), print and measure 
systolic PA, diastolic PA, mean PA pressures and 
mark on paper where readings are interpreted 
for each PA with PE. 
PAS/PAD/PA Mean/SvO2/Modified Fick CO/CI 
SpO2 (O2 Sat by pulse oximetry) 
Check ACT – if less than 200 seconds, give additional bolus of heparin 
Study Schema 
Part 1 
Please note any 
study 
requirements 
that are tests 
performed 
according to the 
standard of care 
may be 
performed prior 
to informed 
consent 


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Transfer to ICU 
PAS / PAD / PA Mean q 30” from tip of 
BEC Catheter(s) (R and L if bilateral) 
Mixed Venous SvO2 q 2 hrs in ICU from tip of BEC Catheter, 
continuous SpO2 by Pulse Oximeter  
Stop r-tPA Infusion(s) at approximately  
8 hrs through BEC Basket Infusion Port(s).  
Once r-tPA infusion is complete, maintain patency 
through the BEC by replacing r-tPA with heparinized 
saline infusion using the infusion pump, at TKO  
Stop Heparin GTT. 
Administer Lovenox 
1mg/kg Sub-Q starting 
45min (±15 min) after 
stopping r-tPA, then 
every 12 hrs (±30 min) 
until AFTER 
completion of the 48-
hour CTA. 
Return to IR/Cath Lab 
Remove BEC catheter(s) 
PAS/PAD/PA Mean/SvO2/Modified Fick CO/CI / SpO2  
Echocardiogram 24 Hrs after completion of 
r-tPA infusion 
Maintain Lovenox through completion of 
CTA scan 
Fibrinogen, Physical exam at completion of 
infusion 
Return to Floor or Unit MD Determines Is Appropriate  
Study Schema 
Part 2 
Patient 
Management 
Post BEC 
Placement 
Post r-tPA Infusion 
Starting 
CTA 48 Hrs (±6 Hrs) after  
completion of r-tPA infusion 
If waveform is dampened, record the time 
when the waveform becomes phasic and print 
and mark on the waveform where the SPA, 
DPA and mean PA pressures are interpreted. 


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without written permission from Thrombolex, Inc. 
APPENDIX 21.3 
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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without written permission from Thrombolex, Inc. 
APPENDIX 21.4    
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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without written permission from Thrombolex, Inc. 
APPENDIX 21.5  
CORE LAB PROTOCOLS 
 
(The core lab protocols are an appendix to the protocol and is provided separately.) 
`