The PEERLESS Study
Phase: NA
Conditions: Pulmonary Embolism, Pulmonary Thromboembolism
Sponsor: Inari Medical

Cover Page 
 
PEERLESS Study 
Protocol v. 4.0 
23AUG2023 
 
NCT05111613 

Inari Medical 
FlowTriever Retrieval/Aspiration System and CDT 
Version 4.0 
August 23, 2023 
 
 
 
 
 
 
PEERLESS Study (Protocol 21-002) 
CONFIDENTIAL 
Page 1 of 70 
 
 
 
PEERLESS Study 
 
A prospective, multicenter, randomized controlled trial of the FlowTriever System compared to Catheter-Directed 
Thrombolysis (CDT) for use in the treatment of acute pulmonary embolism. The trial includes a non-randomized 
cohort of subjects with an absolute contraindication to thrombolysis. 
 
 
 
 
Devices: FlowTriever® Retrieval/Aspiration System and CDT 
Protocol Number: 21-002 
Version: 4.0 
August 23, 2023 
Sponsor 
Inari Medical 
6001 Oak Canyon, Suite 100 
Irvine, CA 92618 
USA 
 
European Office 
Inari Medical Europe GmbH 
St. Jacob-Strasse 7 
4052 Basel 
Switzerland 
CONFIDENTIALITY STATEMENT 
This Clinical Investigation Plan and all attachments are considered confidential information. The contents must not 
be disclosed, unless authorized in writing by Inari Medical, except that this document may be disclosed to the 
appropriate Institutional Review Board (IRB) / Ethics Committee (EC) with similar requests for maintenance of 
confidentiality. All data and study results are similarly subjected to the same disclosure restrictions as the 
investigational plan, as stated above. All copies of this investigational plan remain the property of Inari Medical.  
 

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 CONTENTS 
1. 
INTRODUCTION AND BACKGROUND .................................................................................................................. 15 
Diagnosis of Pulmonary Embolism ..................................................................................................................... 15 
Risk Stratification of Pulmonary Embolism ......................................................................................................... 16 
Risk-Based Treatment Options For Pulmonary Embolism .................................................................................. 18 
Limitations of Currently Available Therapy ........................................................................................................ 21 
2. 
STUDY DEVICES ................................................................................................................................................... 22 
FlowTriever System ............................................................................................................................................ 22 
Regulatory Status ................................................................................................................................................ 22 
Manufacturer ...................................................................................................................................................... 22 
Indications for Use and Intended Use ................................................................................................................. 22 
Device Description .............................................................................................................................................. 23 
Catheter-Directed Thrombolysis (CDT) ............................................................................................................... 25 
Conventional CDT Catheters ............................................................................................................................... 25 
Ultrasound-Assisted CDT Catheters .................................................................................................................... 26 
3. 
PRIOR INVESTIGATIONS ...................................................................................................................................... 27 
FlowTriever System ............................................................................................................................................ 27 
FLARE Study Design and Summary of Results ..................................................................................................... 27 
FLASH Study Design, Status, and Results ............................................................................................................ 28 
FLAME Study Design and Status.......................................................................................................................... 29 
Additional Published Results............................................................................................................................... 30 
Catheter-Directed Thrombolysis ........................................................................................................................ 30 
Conventional Catheter-Directed Thrombolysis (CDT) ......................................................................................... 30 
Ultrasound-assisted Catheter-Directed Thrombolysis (USAT) ............................................................................ 30 
4. 
STUDY OBJECTIVE ............................................................................................................................................... 32 
5. 
OUTCOME VARIABLES ......................................................................................................................................... 32 
Primary Endpoint Definition ............................................................................................................................... 32 
Definition of Intracranial Hemorrhage................................................................................................................ 32 
Definition of Major Bleeding ............................................................................................................................... 32 
Definitions of Clinical Deterioration and Bailout ................................................................................................ 32 
Definition of ICU Admission and ICU Length of Stay ........................................................................................... 34 
Secondary Endpoints .......................................................................................................................................... 34 
6. 
STUDY DESIGN .................................................................................................................................................... 35 
Study Population ................................................................................................................................................ 35 

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Point of Enrollment ............................................................................................................................................. 36 
Enrollment considerations in study design ......................................................................................................... 36 
Inclusion Criteria ................................................................................................................................................. 38 
Exclusion Criteria ................................................................................................................................................ 38 
7. 
ASSESSMENTS AND FOLLOW UP SCHEDULE ....................................................................................................... 39 
Schedule of Assessments .................................................................................................................................... 39 
Baseline Assessments ......................................................................................................................................... 41 
Allocation and Randomization ............................................................................................................................ 41 
Index Procedure.................................................................................................................................................. 41 
Follow up Assessments ....................................................................................................................................... 42 
Unscheduled Follow up Visits ............................................................................................................................. 43 
Withdrawals and Lost to Follow up .................................................................................................................... 43 
COVID-19 Effect on Research ............................................................................................................................. 44 
8. 
RISK ANALYSIS ..................................................................................................................................................... 44 
Risks to Subjects ................................................................................................................................................. 44 
Risk Mitigation .................................................................................................................................................... 44 
Study Justification ............................................................................................................................................... 44 
9. 
SAFETY ASSESSMENT .......................................................................................................................................... 45 
Defining Adverse Events ..................................................................................................................................... 45 
Defining Adverse Device Effect (ADE) ................................................................................................................. 45 
Defining Serious Adverse Event (SAE) ................................................................................................................ 45 
Defining Serious Adverse Device Effect (SADE) .................................................................................................. 46 
Defining Unanticipated/Anticipated Serious Adverse Device Effect (USADE/ASADE) ....................................... 46 
Defining Unanticipated Adverse Device Effect (UADE) ...................................................................................... 46 
Device Deficiency (DD) ....................................................................................................................................... 46 
Event Severity ..................................................................................................................................................... 46 
Event Relationship .............................................................................................................................................. 47 
Adverse Event Reporting .................................................................................................................................... 47 
Product Complaint Reporting ............................................................................................................................. 48 
10. STATISTICS & DATA ANALYSIS ............................................................................................................................. 49 
Sample Size ......................................................................................................................................................... 49 
Statistical Methodology ...................................................................................................................................... 49 
11. STUDY MANAGEMENT CONSIDERATIONS .......................................................................................................... 50 
Protocol Modifications ....................................................................................................................................... 50 
Protocol Deviations ............................................................................................................................................ 50 
Information for Study Personnel ........................................................................................................................ 50 
12. STUDY ADMINISTRATION .................................................................................................................................... 51 

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Site Selection and Qualification .......................................................................................................................... 51 
Site Initiation....................................................................................................................................................... 51 
Site Monitoring ................................................................................................................................................... 51 
Site Close-Out ..................................................................................................................................................... 51 
Study Termination .............................................................................................................................................. 51 
Data Handling and Recordkeeping ..................................................................................................................... 52 
Completing, Signing and Archiving Case Report Forms ...................................................................................... 52 
Data Management and Archiving ....................................................................................................................... 52 
Direct Access to Source Data/Documentation ................................................................................................... 52 
13. ETHICS AND CONFIDENTIALITY ........................................................................................................................... 53 
Informed Consent ............................................................................................................................................... 53 
Institutional Review Board (IRB) / Ethics Committee (EC) .................................................................................. 53 
Study Subject Confidentiality.............................................................................................................................. 53 
Independent Image Review and Image Transfer ................................................................................................ 54 
Investigator Responsibilities ............................................................................................................................... 54 
14. ELECTRONIC DATA .............................................................................................................................................. 54 
15. Publication Of Trial Results ................................................................................................................................. 54 
16. Future Use of Data For Research Purposes ........................................................................................................ 55 
17. TERMS AND DEFINITIONS ................................................................................................................................... 55 
18. REFERENCES ........................................................................................................................................................ 62 
19. APPENDIX 1 ......................................................................................................................................................... 66 
Table A1: Known Risks For FlowTriever System * .............................................................................................. 66 
Table A2: Known Risks For Catheter-Directed Thrombolysis** ......................................................................... 68 
20. SIGNATURE APPROVAL PAGE.............................................................................................................................. 70 
 
Listing of Tables 
Table 1 VTE-BLEED Algorithm ...................................................................................................................................... 36 
 
Listing of Figures 
Figure 1 European Society of Cardiology Risk Stratification ........................................................................................ 18 
Figure 2 Triever Catheters ........................................................................................................................................... 23 
Figure 3 Large Bore Syringe ......................................................................................................................................... 23 
Figure 4 FlowTriever Catheter (3-disk Configuration Shown) ..................................................................................... 24 

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Figure 5 The FlowSaver Blood Return System ............................................................................................................. 24 
Figure 6 Cragg-McNamara Infusion Catheter .............................................................................................................. 25 
Figure 7 Uni-Fuse Infusion Catheters .......................................................................................................................... 26 
Figure 8 EKOS Endovascular System ............................................................................................................................ 26 
Figure 9 Subject Enrollment Flowchart ....................................................................................................................... 37 
 
 
 

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 PROTOCOL SIGNATURE PAGE 
 
 
 
 
 
 
Investigator Name 
 
Title 
 
 
 
Site Name 
 
Site Number 
 
 
 
I have read the protocol and agree that it contains all necessary details for carrying out this study. I will conduct 
the study as outlined therein.  
I will provide copies of the protocol and all information on the device relating to past non-clinical and clinical 
experience, which were furnished to me by the Sponsor, to all physicians and other study personnel responsible to 
me who participate in this study and will discuss this material with them to ensure that they are fully informed 
regarding the device and the conduct of the study. 
I agree to keep records on all patient information (e.g., source documents and informed consent forms) and all 
other information collected during the study, in accordance with local and national regulations. 
 
 
 
 
Investigator’s Signature 
 
 
Date 
 
 
 
 

Inari Medical 
FlowTriever Retrieval/Aspiration System and CDT 
Version 4.0 
August 23, 2023 
 
 
 
 
 
 
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 SYNOPSIS 
Protocol Number  
21-002 
Study Title 
PEERLESS Study 
Study Devices 
FlowTriever Retrieval/Aspiration System and any commercially available Catheter-
Directed Thrombolysis (CDT) System 
Regulatory Status 
The FlowTriever System is FDA-cleared in the United States for the treatment of 
Pulmonary Embolism under 510(k) number K211013 and CE Marked for 
distribution in Europe. 
The FlowTriever Retrieval/Aspiration System is indicated for: 
• 
The non-surgical removal of emboli and thrombi from blood vessels. 
• 
Injection, infusion, and/or aspiration of contrast media and other fluids 
into or from a blood vessel. 
The FlowTriever Retrieval/Aspiration System is intended for use in the peripheral 
vasculature and for the treatment of pulmonary embolism. 
Triever Catheters (Triever 16, Triever 20, Triever 20 Curve, and Triever 24) are also 
intended for use in treating clot in transit in the right atrium but not in conjunction 
with FlowTriever Catheters. 
The study will allow any market cleared CDT systems to be used per local 
regulations.  These products may include:  
• 
Cragg-McNamara™ Micro Therapeutics Infusion Catheter (Medtronic) 
• 
Uni-Fuse™ (AngioDynamics) 
• 
EkoSonic (EKOS™) Endovascular System (Boston Scientific) 
Sponsor 
Inari Medical Inc. 
6001 Oak Canyon, Suite 100 
Irvine, CA 92618 (USA) 
 
European Office 
Inari Medical Europe GmbH 
St. Jacob-Strasse 7 
4052 Basel 
Switzerland 
Study Objective 
The primary study objective is to compare the clinical outcomes of patients treated 
with the FlowTriever System versus Catheter-Directed Thrombolysis (CDT) for use 
in the treatment of acute pulmonary embolism (PE).  

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Study Population 
RCT Cohort: Up to 550 subjects with acute PE will be enrolled and randomized at 
up to 60 study sites. All subjects who sign informed consent and who meet all of 
the baseline inclusion criteria and none of the exclusion criteria will be randomized 
(1:1, FlowTriever or CDT).  
• 
One-to-one (1:1) randomization will be stratified by bleeding risk, as 
measured by the VTE-BLEED score3.   
• 
Stratification by the VTE-BLEED algorithm will occur automatically in the 
Electronic Data Capture (EDC) system upon data entry, and randomization 
will be assigned accordingly.  
Contraindication Cohort: Up to 150 additional subjects who meet study eligibility 
criteria and who have an absolute contraindication to thrombolytics, whose initial 
planned primary treatment strategy includes FlowTriever, will be evaluated as part 
of the Contraindication Cohort.  The same RCT Cohort clinical assessments and 
follow up schedule will be administered in this Contraindication Cohort. 
Number of Sites 
This study will be conducted at up to 60 study sites (locations in US, UK, and/or 
Europe). 
Study Design 
This study is a prospective, multicenter, randomized controlled trial of the 
FlowTriever System compared to CDT for acute PE, and includes a non-randomized 
cohort for subjects with an absolute contraindication to thrombolytics. The study 
will collect data on demographics, comorbidities, details from the PE diagnosis and 
treatment, and clinical outcomes through 30-day follow up. 
Randomized Controlled Trial Cohort (RCT Cohort): 
This study is a prospective, multicenter, randomized controlled trial of the 
FlowTriever System compared to Catheter-Directed Thrombolysis (CDT) for 
treatment of acute PE. 
Non-Randomized Absolute Contraindication to Thrombolytics Cohort 
(Contraindication Cohort): 
Subjects who meet study eligibility criteria and who have an absolute 
contraindication to thrombolytics, whose initial planned primary treatment 
strategy includes FlowTriever, will be evaluated as part of the Contraindication 
Cohort.  The same RCT Cohort clinical assessments and follow up schedule will be 
administered in this Contraindication Cohort. 

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Primary Endpoint 
The primary endpoint is a composite clinical endpoint constructed as a win ratio, a 
hierarchy of the following, assessed at hospital discharge or at 7 days after the 
index procedure, whichever is sooner: 
1. All-cause mortality, or 
2. Intracranial hemorrhage (ICH), or 
3. Major bleeding per ISTH definition4, or  
4. Clinical deterioration defined by hemodynamic or respiratory worsening, 
and/or escalation to a bailout therapy, or 
5. ICU admission and ICU length-of-stay during the index hospitalization and 
following the index procedure. 
Secondary Endpoints 
The secondary endpoints of the study will assess safety, effectiveness, and utility 
measures, as follows: 
• 
Composite clinical endpoint constructed as a win ratio hierarchy of the 
following four components, assessed at hospital discharge or at 7 days 
after the index procedure, whichever is sooner: 
o 
All-cause mortality, or 
o 
Intracranial hemorrhage (ICH), or 
o 
Major bleeding per ISTH definition4, or  
o 
Clinical deterioration defined by hemodynamic or respiratory 
worsening, and/or escalation to a bailout therapy 
• 
Individual components of the win ratio composite endpoint, assessed at 
hospital discharge or at 7 days after the index procedure, whichever is 
sooner: 
o 
All-cause mortality 
o 
Intracranial hemorrhage (ICH) 
o 
Major bleeding per ISTH4 definition 
o 
Clinical deterioration defined by hemodynamic or respiratory 
worsening, and/or escalation to a bailout therapy 
o 
ICU admission and ICU length of stay during the index 
hospitalization and following the index procedure 
• 
All-cause mortality within 30 days from index procedure 
• 
PE-related and all-cause readmission within 30 days from index procedure 
• 
Device and drug-related serious adverse events through the 30 day visit 
• 
Clinically Relevant Non-Major (CRNM) and Minor bleeding events through 
hospital discharge or at 7 days after the index procedure, whichever is 
sooner 
• 
Change in right-ventricular/left-ventricular (RV/LV) ratio from baseline to 
24 hour visit, as measured by echocardiography or CT 
• 
mMRC Dyspnea score at 24 hour visit and 30 day visit 
• 
Length of total hospital stay and post-index-procedure hospital stay (to a 
maximum of 30 days) 
• 
Disease-specific and general health-related quality of life at the 30 day 
visit (PEmb-QoL and EQ-5D-5L) 

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Inclusion Criteria 
Subjects must meet each of the following criteria to be included in the study: 
1. Age ≥ 18 years 
2. Echo, computed tomographic pulmonary angiography (CTPA), or 
pulmonary angiographic evidence of any proximal filling defect in at least 
one main or lobar pulmonary artery 
3. Including ALL of the following: 
a. Clinical signs and symptoms consistent with acute PE, or PESI 
class III-V, or sPESI ≥1 
AND 
b. Hemodynamically stable 
AND 
c. 
RV dysfunction on echocardiography or CT 
AND  
d. Any one or more of the following present at the time of 
diagnosis:  
i. Elevated cardiac troponin levels 
ii. History of heart failure 
iii. History of chronic lung disease 
iv. Heart rate ≥110 beats per minute 
v. SBP <100mmHg  
vi. Respiratory rate ≥30 breaths per minute 
vii. O2 saturation <90% 
viii. Syncope related to PE 
ix. Elevated lactate 
4. Intervention planned to begin within 72 hours of the later of either  
a. Confirmed PE diagnosis 
OR 
b. If transferring from another hospital, arrival at the treating 
hospital 
5. Symptom onset within 14 days of confirmed PE diagnosis 
Exclusion Criteria 
Subjects will be excluded from the study for any of the following criteria:  
1. Unable to anticoagulate with heparin, enoxaparin or other parenteral 
antithrombin 
2. Index presentation with hemodynamic instability that are part of the high-
risk PE definition in the ESC Guidelines 20191, including ANY of the 
following: 
a. Cardiac arrest 
OR 
b. Systolic BP < 90 mmHg or vasopressors required to achieve a BP 
≥90 mmHg despite adequate filling status, AND end-organ 
hypoperfusion 
OR 
c. 
Systolic BP < 90 mmHg or systolic BP drop ≥40 mmHg, lasting 
longer than 15 min and not caused by new-onset arrhythmia, 
hypovolemia, or sepsis 
3. Known sensitivity to radiographic contrast agents that, in the 
Investigator’s opinion, cannot be adequately pre-treated 

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4. Imaging evidence or other evidence that suggests, in the opinion of the 
Investigator, the patient is not appropriate for catheter-based intervention 
(e.g., inability to navigate to target location, clot limited to 
segmental/subsegmental distribution, predominately chronic clot)  
5. Patient has right heart clot in transit identified at baseline screening  
6. Life expectancy < 30 days (e.g., stage 4 cancer or severe COVID-19 
infection), as determined by the Investigator 
7. Current participation in another drug or device study that, in the 
Investigator’s opinion, would interfere with participation in this study 
8. Current or history of chronic thromboembolic pulmonary hypertension 
(CTEPH) or chronic thromboembolic disease (CTED) diagnosis, per ESC 
2019 guidelines1  
9. Invasive systolic PA pressure ≥70 mmHg prior to study device entering the 
body 
10. Administration of bolus or drip/infusion thrombolytic therapy or 
mechanical thrombectomy for the index PE event within 48 hours prior to 
enrollment   
11. Ventricular arrhythmias refractory to treatment at the time of enrollment 
12. Known to have heparin-induced thrombocytopenia (HIT) 
13. Subject has any condition for which, in the opinion of the Investigator, 
participation would not be in the best interest of the subject (e.g., 
compromise the well-being or that could prevent, limit, or confound the 
protocol-specified assessments). This includes a contraindication to use of 
FlowTriever or CDT System (for example, EKOS System) per local approved 
labeling 
14. Subject has previously completed or withdrawn from this study 
15. Patient unwilling or unable to conduct the follow up visits per protocol. 
Follow Up Schedule 
Subjects will have follow-up evaluations after the Index Procedure at:  
• 
24 hours (24 hours ±8 hours)  
• 
Hospital discharge 
• 
30 days (30 days +15 days) 
Safety Monitoring:  
Clinical Events Committee 
(CEC) 
A Clinical Events Committee (CEC) will be utilized in this study for the purposes of 
adjudicating safety-related primary and secondary endpoints.  Site-reported safety 
and outcome data will be provided to the CEC for review and adjudicated for all 
subjects enrolled in the study. 
Global Principal 
Investigators 
Wissam Jaber, M.D. and Carin Gonsalves, M.D. 
European Principal 
Investigator 
Stefan Stortecky, M.D., MPH FESC 
 
 
 

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 ABBREVIATIONS  
Abbreviation 
Term 
AC 
Anticoagulation 
ADE 
Adverse device effect 
AE 
Adverse event 
AHA 
American Heart Association 
ASADE 
Anticipated serious adverse device effect 
CCU 
Coronary care unit 
CDT 
Catheter-directed thrombolysis 
CEC 
Clinical Events Committee 
CI 
Cardiac Index 
CRNM 
Clinically Relevant Non-Major 
CT 
Computed Tomography 
CTED 
Chronic thromboembolic disease 
CTEPH 
Chronic thromboembolic pulmonary hypertension 
CTPA 
Computed tomographic pulmonary angiography 
DD 
Device deficiency  
DVT 
Deep venous thrombosis 
EBL 
Estimated Blood Loss 
ECMO 
Extracorporeal membrane oxygenation 
eCRFs 
Electronic case report forms 
ED 
Emergency Department 
EKOS 
EkoSonic catheter system 
ESC 
European Society of Cardiology 
EC 
Ethics Committee 

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Abbreviation 
Term 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
FLAME 
FlowTriever for Acute Massive Pulmonary Embolism 
FLARE 
FlowTriever Clinical Embolectomy Clinical Study 
FLASH 
FlowTriever All-Comer Registry for Patient Safety and Hemodynamics 
FT 
FlowTriever 
GDPR 
General Data Protection Regulation 2016/679 
H-FABP 
Heart type fatty acid binding 
HGB 
Hemoglobin 
HIPAA 
Health Insurance Portability and Accountability Act 
HIT 
Heparin-induced thrombocytopenia 
ICF 
Informed consent form 
ICH 
Intracranial hemorrhage 
ICU 
Intensive Care Unit 
IFU 
Instructions for use 
IRB 
Institutional review board 
ISTH 
International Society on Thrombosis and Haemostasis 
LMWH 
Low molecular weight heparin 
LOS 
Length of stay 
LV 
Left ventricle 
MAE 
Major adverse events 
MEC 
Medical Ethics Committee 
mMRC  
Modified Medical Research Council Dyspnea Scale 
PA 
Pulmonary Artery 

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Abbreviation 
Term 
PAP 
Pulmonary Artery Pressure 
PAPi 
Pulmonary Artery Pulsatility Index 
PE 
Pulmonary Embolism 
PEmb-QOL 
Pulmonary Embolism Quality of Life 
PESI 
Pulmonary Embolism Severity Index 
PHI 
Protected Health Information 
QOL 
Quality of life 
RA 
Right Atrial 
RV 
Right ventricle 
RV/LV 
Right ventricular to left ventricular diameter ratio 
RVSWI 
Right ventricular stroke work index 
SAE 
Serious adverse event 
SADE 
Serious adverse device effect 
SIV 
Site initiation visit 
sPAP 
Systolic Pulmonary Artery Pressure 
sPESI 
Simplified Pulmonary Embolism Severity Index 
SVI 
Stroke volume index 
tPA 
Tissue plasminogen activator 
TPVR 
Total pulmonary vascular resistance 
TTE 
Transthoracic echocardiography 
UADE 
Unanticipated adverse device effect 
UAT 
Ultrasound-accelerated thrombolysis 
USADE 
Unanticipated serious adverse device effect 
USAT 
Ultrasound-assisted thrombolysis 

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Abbreviation 
Term 
VTE 
Venous thromboembolism 
1. INTRODUCTION AND BACKGROUND  
Pulmonary embolism (PE) is a debilitating and potentially lethal disease, leading to an estimated 300,000 
hospitalizations per year in the US, and over 400,000 PE events in Europe in 2004 with 10-30% mortality.5-7 PE and 
deep vein thrombosis (DVT) are the 2 main clinical consequences of venous thromboembolism (VTE), which 
together lead to over 500,000 annual hospitalizations in the US, and a similar number in Europe.5, 7 Data from the 
Nationwide Inpatient Sample from 1993-2012 showed that US hospital admissions for PE rose from 23 per 100,000 
in 1993 to 65 per 100,000 in 2012.8 While a reduction in mortality was seen over that time period, mortality in 
2012 still ranged from 1.6% to 39.1%, depending on the severity of the disease.8  VTE is also the leading cause of 
preventable in-hospital death.9, 10  
PE occurs when venous thrombi travel from the peripheral veins, through the right heart, and lodge in the 
pulmonary arterial system. The emboli often arise from existing DVTs of the legs, but they may also initiate within 
the large veins of the upper extremities. While small PEs may remain asymptomatic and go unnoticed, larger 
emboli can result in significant pulmonary artery obstruction, leading to right heart decompensation and mortality. 
In fact, because VTE may remain undetected in the initial stages, sudden death is the first symptom of PE in up to 
25% of cases.6 PE may also occur in a repeated fashion, over months or even years, insidiously obliterating the 
pulmonary arterial outflow to culminate in debilitating pulmonary hypertension and the syndrome known as 
chronic thromboembolic pulmonary hypertension (CTEPH). Due to high mortality and debilitating long-term 
outcomes, better treatment options that provide rapid hemodynamic relief and reduction in acute mortality, as 
well as improved long-term functional outcomes, are clearly needed.  
DIAGNOSIS OF PULMONARY EMBOLISM 
Clinical signs of PE tend to be non-specific, and include dyspnea, chest pain, elevated heart rate, and syncope. 
Because of the non-specific nature of PE symptoms, assessment of predisposing factors for VTE becomes an 
important component of the clinical work-up. These factors include recent trauma or surgery, prolonged inactivity, 
active cancer, and previous VTE. Several predictive scores have been developed to help diagnosis and prediction of 
disease severity, including the Wells1 and Geneva11 scores, but studies suggest the predictive value of these scores 
fared no better than empirical clinical evidence, or clinical “gestalt”.12, 13 
Once PE is suspected based on clinical signs and predisposing factors, a more definitive diagnosis as well as 
assessment of severity can be obtained by imaging. The most informative approach is computed tomography 
pulmonary angiography (CTPA), which is now readily available at most clinical sites with rapid acquisition time. The 
Prospective Investigation On Pulmonary Embolism Diagnosis (PIOPED) II study demonstrated a sensitivity of 83% 
and a specificity of 96% for CTPA in diagnosing PE.14 CTPA can reveal right ventricle (RV) dilatation and provide an 
RV/left ventricle (LV) ratio, which is an independent predictor of an adverse outcome when RV/LV ≥ 0.9.15 In 
addition, it provides visualization of both location and size of emboli within the pulmonary arterial system down to 
the subsegmental level. 
Transthoracic echocardiography (TTE) can be effective at detecting right heart dysfunction and RV dilatation 
associated with PE, along with other parameters, including estimated right atrial (RA) pressure and RV systolic 
pressure. It can also detect RA clot-in-transit, which if left untreated, may result in acute PE. 
Laboratory biomarkers can contribute to both the diagnosis and the risk assessment of PE patients. Plasma D-
dimer concentration can be elevated in patients with acute thrombosis, and it has a high negative predictive value 

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for PE.1 However, its positive predictive value is low,16 and elevated D-dimer is seen in other disease states, such as 
cancer or severe infection. Thus, a negative test safely excludes PE in patients with low clinical probability of the 
disease, but further imaging is necessary when the D-dimer test is positive.1 
The guideline-recommended diagnosis and treatment of PE depends on its severity, which is defined by the risk of 
mortality. This risk is tightly correlated with the hemodynamic consequences of the embolism, namely, acute RV 
dysfunction. RV dysfunction is the principal determinant of a patient’s clinical course.17 The risk of hemodynamic 
compromise is related to the interplay between the size of the embolus and the baseline cardiorespiratory state of 
the patient. For instance, a PE of moderate size in a healthy patient may be unassociated with hemodynamic 
compromise while the same embolus in an elderly patient with preexisting cardiac disease may result in fulminant 
right heart decompensation and mortality. In this regard, the severity of pulmonary embolism is only partially 
represented by the presenting hemodynamic condition of the patient, and baseline comorbidities should be 
considered. 
RISK STRATIFICATION OF PULMONARY EMBOLISM  
Once the diagnosis of PE has been made, it becomes essential to identify those patients at highest risk for 
mortality in order to triage them to advanced therapies that can quickly reduce the right heart strain and thus the 
risk of mortality. A variety of indices have been used to predict outcomes following PE. The Pulmonary Embolism 
Severity Index (PESI) has been well-validated.18 PESI risk strata I and II patients have a low risk of 30-day mortality. 
A simplified PESI score, sPESI, was also developed and validated.19-21 Patients with an sPESI score of 0 have a very 
low risk of early adverse outcome. Adding a negative cardiac troponin further increases the negative predictive 
value of the scores.20 It should be noted, however, that the PESI and sPESI risk stratifications were developed as 
epidemiologic tools and were not designed to guide the management of PE. 
Approximately 30-60% of acute PE patients have elevated cardiac troponins I or T22, 23 and elevated troponin is 
associated with an increased risk in mortality, even in patients who initially present as hemodynamically stable.24 
In addition, B-type natriuretic peptide (BNP) and N-terminal (NT) proBNP have low positive predictive value for 
mortality in normotensive PE patients but have a high sensitivity and a negative predictive value for ruling out PE.25 
Additional biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and lactate, have been studied and 
shown to have some utility in the diagnosis of PE, risk assessment, or both,26, 27 but these have not yet become 
routinely used. 
There are several well-established guidelines for classifying the mortality risk and PE severity for affected patients. 
The most recent and widely used of these are the American Heart Association Scientific Statement on 
Interventional Therapies for Acute Pulmonary Embolism28 and the European Society of Cardiology Guidelines for 
Diagnosis and Management of Acute Pulmonary Embolism.1 
American Heart Association. The 2019 American Heart Association (AHA) Scientific Statement on Interventional 
Therapies for Acute Pulmonary Embolism reiterates the established classification of PE into three traditional 
categories utilized in the literature: massive, submassive, and low-risk.28   
• 
Massive PE is defined as hypotension with systolic blood pressure < 90 mm Hg, a drop of > 40 mmHg for 
at least 15 minutes or requiring vasopressor support. Mortality is ~30% within 1 month. 
• 
Submassive PE is defined as RV strain without hypotension, with RV strain identified by either RV 
dysfunction on CTPA or myocardial necrosis as measured by elevated troponins or BNPs. Mortality varies 
widely in published studies, ranging between 3 - 15% over 7 - 90 days. 
• 
Low-risk PE is a PE that falls short of the criteria for submassive PE, in other words, a PE without RV 
dysfunction or elevation of biomarkers. Mortality at one month is ~1% in this group. 

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While these categories correlate roughly with the risk of mortality, the AHA statement stresses that concurrent 
comorbidities must be accounted for in the prediction of mortality and the decision for treatment options. While 
most low-risk patients do well on anti-coagulation (AC) alone, advanced therapies should be increasingly 
considered as the mortality/risk stratification level increases, with the possible treatment risks weighed against the 
PE severity and mortality risk. As such, the development of new therapies with lower risk profiles could allow these 
advanced therapies to be a compelling option for more than just the highest risk patients. Potential but unproven 
benefits of treating intermediate-risk (sub-massive) PE patients beyond the immediate hemodynamic relief and 
mortality benefit seen when treating high-risk patients may be improved long-term functional outcomes and 
prevention of CTEPH. 
European Society of Cardiology. The 2019 European Society of Cardiology (ESC) Guidelines for Diagnosis and 
Management of Acute Pulmonary Embolism specified risk stratification using combinations of hemodynamic 
instability, clinical parameters of PE severity and/or co-morbidity, RV dysfunction by imaging, and cardiac troponin 
levels (Figure 1).1 This risk stratification differs slightly from the AHA stratification in the definition, and further 
stratification, of the sub-massive (AHA), or intermediate-risk (ESC) category into intermediate-high and 
intermediate-low categories, resulting in four risk levels. 
High-risk PE patients present with acute hemodynamic instability and imaging evidence of RV dysfunction, 
analogous to the massive category in the AHA guidelines. These patients present in shock and have PESI scores III 
or greater or sPESI scores greater than 0 (if assessed) and positive cardiac troponins indicative of myocardial 
necrosis (if assessed). An intermediate-risk category is defined by the ESC guidelines, analogous to the submassive 
category in the literature and AHA guidelines. The intermediate-risk subgroup is further divided into intermediate-
high-risk and intermediate-low-risk subcategories, depending on whether both RV dysfunction and elevated 
cardiac troponin levels are present (intermediate-high-risk) or only one or neither of the two are present 
(intermediate-low-risk). The last category is the low-risk group and is similar to the AHA low-risk category. These 
patients present without hemodynamic compromise, have low PESI/sPESI scores, and normal RV imaging or 
laboratory assessments when they are performed.  

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RISK-BASED TREATMENT OPTIONS FOR PULMONARY EMBOLISM  
Anticoagulation (AC) 
AC is the mainstay of therapy for VTE, directed at decreasing the risk of recurrent embolic events and propagation 
of existing thrombi. Upon suspicion of PE, AC should be started immediately with either subcutaneous 
 
Figure 1 European Society of Cardiology Risk Stratification 
From Konstantinides et al.1 
 
aOne of the following clinical presentations: cardiac arrest, obstructive shock (systolic BP <90 mmHg or 
vasopressors required to achieve a BP ≥ 90 mmHg despite an adequate filling status, in combination with end-
organ hypoperfusion), or persistent hypotension (systolic BP <90 mmHg or a systolic BP drop ≥ 40 mmHg for 
>15 min, not caused by new-onset arrhythmia, hypovolaemia, or sepsis). 
bPrognostically relevant imaging (TTE or CTPA) findings in patients with acute PE. 
cElevation of further laboratory biomarkers, such as NT-proBNP ≥ 600 ng/L, H-FABP ≥ 6 ng/mL, or copeptin ≥ 
24 pmol/L, may provide additional prognostic information. These markers have been validated in cohort 
studies but they have not yet been used to guide treatment decisions in randomized controlled trials. 
dHaemodynamic instability, combined with PE confirmation on CTPA and/or evidence of RV dysfunction on 
TTE, is sufficient to classify a patient into the high-risk PE category. In these cases, neither calculation of the 
PESI nor measurement of troponins or other cardiac biomarkers is necessary. 
eSigns of RV dysfunction on TTE (or CTPA) or elevated cardiac biomarker levels may be present, despite a 
calculated PESI of I_II or an sPESI of 0.2 Until the implications of such discrepancies for the management of PE 
are fully understood, these patients should be classified into the intermediate-risk category.  
BP = blood pressure; CTPA = computed tomography pulmonary angiography; H-FABP = heart-type fatty acid-
binding protein; NT-proBNP = N-terminal pro B-type natriuretic peptide; PE = pulmonary embolism; PESI = 
Pulmonary Embolism Severity Index; RV = right ventricular; sPESI = simplified Pulmonary Embolism Severity 
Index; TTE = transthoracic echocardiogram 

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administration of low-molecular weight heparin or fondaparinux, with a Class 1C recommendation in the ESC 
guidelines.1 For low-risk patients, AC therapy on an outpatient basis may be sufficient if proper outpatient care and 
medication compliance can be assured (Class IIa-A recommendation, ESC guidelines).1 
Open Surgical Thrombectomy  
Open surgical thrombectomy was perhaps the first definitive interventional treatment for PE. Open surgical 
thrombectomy can result in rapid, life-saving hemodynamic improvement in patients with significant PE.29, 30 
However, it is a major invasive procedure, fraught with complications in unstable patients. The in-hospital 
mortality rate is more than 25%, although this figure must be considered in the context of alternative therapies in 
this high-risk group. No randomized trials have been performed to compare the outcome with alternate therapies 
in similar patient populations. For these reasons, AHA and ESC guidelines suggest that open surgical intervention 
be reserved for hemodynamically-unstable patients with contraindications to thrombolysis.1, 28 However, selected 
indications remain appropriate for open thrombectomy; for example, emboli in transit such as within the right 
heart or a patent foramen ovale. In this regard, the American College of Chest Physicians advocates open surgical 
intervention for patients who are severely compromised such that mortality is likely to occur before thrombolytic 
therapies can improve the patient’s hemodynamic state.31 
Thrombolysis  
While anticoagulation is effective in preventing formation of new thrombus and thus reducing recurrent PE, it does 
little to treat existing thrombus. Pharmacologic lysis of the obstructive pulmonary artery thromboembolism has 
the potential to provide rapid relief of right heart strain, and thus reduce mortality risk, in patients with 
intermediate-risk (submassive) and high-risk (massive) PE, where normalization of right heart function is critical to 
reduce mortality. For this reason, systemic infusion of thrombolytic drugs was evaluated in order to more directly 
reduce the burden of existing thrombus. These thrombolytic drugs consisted of various early-generation 
plasminogen activators, such as urokinase and streptokinase. These enzymatic pharmacologic agents target the 
breakdown of fibrin within acute thrombi. After initial anecdotal success with intravenous urokinase for PE 
reported in 1968 by Sasahara,32 the landmark randomized clinical trials upon which the initial US Food and Drug 
Administration (FDA) approval for urokinase was based demonstrated improved outcome with thrombolysis versus 
anticoagulation for submassive and massive PE.33-38 The benefits were limited to short-term improvement in 
cardiac function, but the studies were not powered to detect mortality differences. For the first time, however, 
lysis of pulmonary artery thrombus was demonstrated to be safe, effective, and appeared advantageous compared 
to anticoagulation alone.  
Systemic Thrombolysis: Over the next five decades, intravenous, systemic thrombolysis was demonstrated to be 
effective in reducing the thrombus load after PE. However, this outcome was achieved at the cost of a five-fold 
increase in major bleeding, which in some cases included intracranial hemorrhage.39-41 These findings remained 
unchanged despite the use of newer modern thrombolytic agents and better periprocedural patient management 
over the years.  
Catheter-Directed Thrombolysis (CDT): Noting the hemorrhagic complications associated with systemic 
thrombolysis for PE, lower-dose, CDT approaches were studied in which catheters were maneuvered into the 
pulmonary arteries to selectively deliver thrombolytics directly to the location of the obstructing thrombus. 
Catheter-directed thrombolysis for PE was the subject of a meta-analysis published in 2009.42 In summary, 
catheter-directed thrombolysis appeared effective and probably safer than the systemic approach. The authors 
recommended that catheter-directed thrombolysis be considered as a first-line therapy for acute, massive PE. 
However, recent work suggests that even a catheter-directed approach may be associated with significant bleeding 
complications,43 although possibly at a lower rate than with systemic treatment.44 

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Ultrasound-Accelerated Thrombolysis: To further enhance the efficacy of CDT, ultrasound technology was 
incorporated into the CDT catheter to accelerate the lytic process by thinning and separating the fibrin strands 
within the thrombus, which led to the development of the EkoSonic catheter system (EKOS™). This ultrasound-
assisted thrombolysis (USAT) approach was evaluated for submassive and massive PE in two multicenter, 
prospective studies, ULTIMA and SEATTLE-II. ULTIMA was a randomized analysis of USAT vs. anticoagulation alone 
in 59 subjects with submassive PE.45 USAT was found to be more effective than anticoagulation in normalizing RV 
function. No intracranial bleeding was observed. The SEATTLE-II trial evaluated 24mg of tissue plasminogen 
activator (tPAa), infused over 24hr in one catheter, or over 12 hours in two catheters, in 150 subjects with 
submassive and massive PE.46 Further refinement of the lytic dose and infusion duration using EKOS was 
conducted in the OPTALYSE PE trial, which contained four study arms with tPA dose from 4 to 12 mg per lung and 
infusion duration from 2-6 hours.47 These studies concluded that catheter-directed pulmonary artery thrombolysis 
with tPA was safe and effective in the treatment of submassive (intermediate-risk) PE, at least with respect to 
reductions in RV/LV ratio, and suggested that lower doses and infusion durations were associated with significant 
RV/LV improvements and clot burden reduction at 48 hours. These conclusions, however, have not been without 
controversy. A 2017 review of 23 studies and 700 subjects found no difference in the rate of bleeding 
complications between USAT and conventional, catheter-directed thrombolysis, 12% with USAT vs. 10% with 
conventional catheter-directed thrombolysis.48 The review, however, documented a trend toward improved 
survival with USAT; mortality rates of 4% vs. 9% in the USAT and conventional thrombolytic subjects, respectively. 
A more recent prospective, randomized controlled trial (SUNSET PE) comparing USAT to CDT demonstrated no 
benefit of USAT compared to CDT.49 It should be noted that use of thrombolytics, whether by conventional or 
USAT approach, typically requires the patient be admitted to the Intensive Care Unit (ICU), due to the elevated 
bleeding risk, for the duration of the perfusion, which can last up to 48 hours. 
Percutaneous Pulmonary Artery Thrombectomy  
Pulmonary artery thrombectomy involves the mechanical removal of the thrombus from the vasculature, either 
through aspiration (suction) or through entrapment of the thrombus in mechanical tools that are then retracted 
after capturing the thrombus. Interest in this purely mechanical approach grew as it offers a rapid treatment 
option in contrast to the relatively slow thrombolytic treatment, without the inherent risk of bleeding 
complications seen with pharmacologic thrombolysis. In addition, percutaneous thrombectomy can be performed 
in the catheterization lab without the need for the ICU stay required during thrombolytic infusion. The lack of ICU 
requirement has been particularly attractive in the time of the Covid-19 pandemic with ICU bed shortages. 
Mechanical thrombectomy also provides a much-needed treatment option for the up-to-50% of PE patients who 
are contraindicated for thrombolytics. This treatment option may also be more effective at removing older 
thrombus, in which much of the fibrin has been replaced with collagen, against which thrombolytic drugs are 
ineffective. Direct pulmonary arterial thrombectomy thus offers the opportunity for rapid removal of thrombus in 
the catheterization lab for a broader range of PE patients without thrombolytic-related bleeding complications. 
Multiple mechanical thrombectomy devices with slightly differing approaches have been developed, although 
none to date have been evaluated in a head-to-head comparison of other treatment options in a randomized trial. 
Treatment Recommendations Based on Risk Stratification 
The risk stratification strategies of both the 2019 AHA Scientific Statement and the 2019 ESC PE Guidelines provide 
a data-driven clinical decision strategy for optimal treatment of PE based on clinical presentation. Treatment of 
low-risk PE patients with no serious co-morbidities or aggravating conditions is straightforward, with data 
supporting early discharge and the use of AC for at least 3 months after diagnosis, with a Class IIa-A 
recommendation in the ESC guidelines.  
 
a Authors of this study refer to the thrombolytic agent as ‘tPA,’ which is presumably alteplase but not specified. 

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Early, aggressive treatment beyond AC therapy is necessary for the massive, or high-risk, PE patient to prevent the 
rapid, downhill spiral that culminates in a patient’s demise. Based on existing clinical data at the time of 
publication, the 2019 ESC guidelines recommend systemic thrombolysis as the treatment choice for high-risk PE, 
with a Class IB recommendation. Surgical pulmonary embolectomy or percutaneous CDT as alternative treatments 
in patients in whom thrombolysis is contraindicated or has failed is given a Class IIa-C recommendation. Of note, 
extracorporeal membrane oxygenation (ECMO) may be considered with any of these treatments to provide 
hemodynamic support in patients with refractory circulatory collapse or cardiac arrest until stabilization is 
achieved.  
More controversial and less well-defined is the treatment of intermediate-risk patients. There has been recent 
enthusiasm for endovascular interventional treatment modalities utilizing catheter-directed thrombolysis, 
ultrasound-accelerated thrombolysis, or mechanical thrombectomy.48, 50-53 Currently, however, there is scant data 
on which to base therapeutic decisions for the intermediate-risk group, as randomized control trials comparing the 
different therapy options is lacking. Based on the current data available, thrombolytic treatment is recommended 
for those submassive, or intermediate-risk, patients with hemodynamic deterioration (Class I-B), but not for 
routine use in all intermediate- or low-risk patients. Surgical or percutaneous thrombectomy is given a “may also 
be considered in these patients” Class IIa-C recommendation.  
LIMITATIONS OF CURRENTLY AVAILABLE THERAPY  
Generally, the AHA Scientific Statement and ESC guidelines agree that the mainstay of treatment for massive and 
submassive PE is anticoagulation and that thrombolysis should be offered to unstable patients.1, 28 They further 
suggest that thrombolytics not be routinely used to treat submassive PE but should instead be considered on a per 
patient basis. The choice between treating the PE patient with standard AC alone versus advanced therapy, as well 
as which advanced therapy to use, should be based on clinical evidence, much of which to date is derived from 
clinical trials and meta-analyses of studies of systemic thrombolysis. While some trials have shown benefit of using 
either systemic or catheter-directed thrombolysis compared to AC alone,39 that benefit is typically offset by an 
increase in major bleeding risk. For this reason, and because many PE patients are contraindicated for 
thrombolytics, advanced treatment options that do not involve a thrombolytic component, such as mechanical 
thrombectomy, are being pursued, but clinical data are lacking.  
While a treatment’s impact on acute hemodynamic parameters is critical for reducing mortality, understanding the 
long-term outcomes and potential impact of unresolved, residual thrombus post-treatment is critically important 
to the long-term morbidity and quality of life of the PE patient. Residual thrombus can lead to post-PE syndrome 
and/or CTEPH in up to 50% of PE patients, with long-term, debilitating impact on functional status and quality of 
life.54-56 Data on residual thrombus post-treatment as well as the incidence of post-PE syndrome and CTEPH 
following the different treatment options is also lacking. 
The goal of a successful interventional procedure is to restore RV outflow through the pulmonary artery, thereby 
disrupting the potentially lethal cascade towards hemodynamic collapse. However, there remains a strong clinical 
need to develop a reliable, rapid, percutaneous method of thrombus removal for the treatment of clinically 
significant acute PE. The need is especially strong for a mechanical method that does not rely on the use of 
thrombolytics, as physicians are reluctant to administer thrombolytics given the high bleeding risk and because 
many patients cannot tolerate lytics. Once the immediate thrombus burden is removed, blood flow is restored and 
the acute physiological effects from pressure overload should begin to dissipate. The FlowTriever System was 
developed to meet this need to rapidly restore blood flow through the pulmonary vasculature in patients 
experiencing acute submassive or massive pulmonary embolism. However, clinical data from prospective, 
randomized control trials are still lacking for FlowTriever and other advanced therapies. The 2019 AHA document 
urges the pursuit of such studies, and suggests several components for these future trials, including patient-centric 
functional quality of life (QOL) outcomes in addition to the traditional outcomes of mortality and hemodynamic 
decompensation.28 

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2. STUDY DEVICES 
Subjects enrolled in this study will undergo PE treatment with either the FlowTriever System or standard 
commercially available CDT devices, depending on each patient’s randomization assignment (or inclusion into the 
Contraindication Cohort). These study devices are reviewed briefly in the following sections.  Future commercially 
available FlowTriever system components or commercially available CDT systems may be included in the study but 
may not be listed here due to current regulatory approval status. 
FLOWTRIEVER SYSTEM 
 
The FlowTriever Retrieval/Aspiration System is a single-use over-the-wire catheter-based system for the minimally 
invasive treatment of thromboemboli in the peripheral vasculature and for the treatment of pulmonary embolism. 
The system is comprised of two main components packaged separately: 
• 
Triever Catheters (available in 3 sizes: 16, 20 (and 20 Curved) and 24 Fr) 
• 
FlowTriever Catheters (available in 4 sizes: 6-10 mm, 11-14 mm, 15-18 mm, and 19-25 mm) 
Triever Catheters (Triever 16, Triever 20, Triever 20 Curve, and Triever 24) are inserted and advanced to the 
thrombus over a pre-placed 0.035" guidewire. After removal of its dilator, thrombus may be removed by aspiration 
with the provided 60 cc VacLok Vacuum syringe. After the procedure is complete, the Triever Catheter is removed 
from the patient.  
Regulatory Status  
The FlowTriever System is FDA-cleared in the United States for the treatment of Pulmonary Embolism under 510(k) 
number K211013 and CE Marked for distribution in Europe. 
Manufacturer 
The FlowTriever System is manufactured by Inari Medical, Inc. The manufacturer location: 
Inari Medical, Inc. 
6001 Oak Canyon, Suite #100 
Irvine, CA 92618 (USA) 
Indications for Use and Intended Use  
The FlowTriever Retrieval/Aspiration System is indicated for: 
• 
The non-surgical removal of emboli and thrombi from blood vessels. 
• 
Injection, infusion, and/or aspiration of contrast media and other fluids into or from a blood vessel. 
The FlowTriever Retrieval/Aspiration System is intended for use in the peripheral vasculature and for the 
treatment of pulmonary embolism. 
Triever Catheters (Triever 16, Triever 20, Triever 20 Curve, and Triever 24) are also intended for use in treating clot 
in transit in the right atrium but not in conjunction with FlowTriever Catheters. 

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Device Description  
The FlowTriever System is a single-use over-the-wire catheter-based system for the minimally invasive treatment 
of thromboemboli in the peripheral vasculature and the treatment of pulmonary embolism. The FlowTriever 
System is composed of two main components: the Triever aspiration catheter and the FlowTriever catheter. The 
FlowTriever System can be used in conjunction with the FlowSaver™ Blood Return System, which is a separate 
product for filtering and reintroducing blood aspirated by the FlowTriever System. Each of these devices is 
described below. 
Triever™ Aspiration Catheters 
The Triever Aspiration Catheter is a large-bore catheter used primarily for controlled aspiration of thromboemboli 
(Fig. 2A). The catheters are available in 16, 20, and 24Fr diameters, which are referred to as the Triever16™ (T16), 
Triever20™ (T20), and Triever24™ (T24) catheters, respectively. The Triever20 Curve™ (T20 Curve) pre-shaped 
catheter is designed with a bend of up to 260° to provide access to challenging anatomy (Fig. 2B) and must be used 
coaxially with the T24 catheter. After the distal end of the Triever catheter is positioned adjacent to thrombus, a 
vacuum is applied to the closed catheter side port via a 60 mL custom large-bore syringe (Fig. 3). Opening the side 
port valve produces an abrupt, high-flow suction to extract thrombus through the Triever catheter and into the 
syringe, while limiting blood loss to 60 mL per aspiration.  
Figure 2 Triever Catheters 
     
 
Figure 3 Large Bore Syringe 
 
FlowTriever™ Catheter 
The FlowTriever catheter, which is designed to be deployed coaxially through the Triever Catheter, consists of a 
flexible shaft attached to distal self-expanding nitinol disks. It is used to macerate and deliver thrombus to the 
Triever catheter for removal via aspiration and is often used for more chronic, wall-adherent thrombus. The 
A 
B 

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FlowTriever catheter is available in multiple configurations. One representative version of the FlowTriever catheter 
consists of 3 disks (Fig. 4) that are available in four sizes ranging in disk diameters from 12.5 to 28.0mm. 
Figure 4 FlowTriever Catheter (3-disk Configuration Shown) 
 
Additional FlowTriever catheters that have different nitinol disk configurations may be used during the course of 
this study depending on the status of regulatory clearances local to each geographic region in which the study is 
conducted. All FlowTriever catheter configurations have the same function to macerate and deliver thrombus to 
the Triever catheter for aspiration. 
A complete description of the FlowTriever System is provided in the Instructions for Use. 
FlowSaver™ Blood Return System 
The FlowSaver Blood Return System is used to filter the aspirated contents of the Large Bore Syringe from a 
FlowTriever System procedure. The provided 60cc syringe is connected to the outlet port and used to aspirate 
blood through the 40 µm filter (Fig. 5). The filtered blood is then re-introduced to the patient through a sheath or 
catheter. It is indicated to be used with the Triever Catheters for autologous blood transfusion.  
 
Figure 5 The FlowSaver Blood Return System 
 
A complete description of the FlowSaver System is provided in the Instructions for Use (FlowSaver is FDA-cleared in 
the United States under 510(k) number K210176). 

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CATHETER-DIRECTED THROMBOLYSIS (CDT) 
Catheter-directed thrombolysis devices are catheters introduced endovascularly and placed at the site of the 
thrombus for localized infusion of thrombolytic drugs, such as various tissue plasminogen activators (tPA), which 
are infused through side holes in the catheter to enhance thrombus dissolution. Due to the bleeding risks 
associated with thrombolytic drugs, patients undergoing CDT are typically admitted to the ICU and immobilized 
during the infusion, then returned to the catheterization lab to assess the degree of thrombus dissolution 
following treatment. Additional thrombolytic infusions may be attempted if the initial infusion resulted in 
insufficient thrombus dissolution.  
Various commercially available endovascular catheters may be used for CDT purposes, including both conventional 
CDT catheters and ultrasound-assisted CDT catheters. These two categories of CDT devices are described briefly in 
the following sections.  
Conventional CDT Catheters 
Conventional CDT catheters rely on their side hole designs to deliver targeted thrombolytic drugs to the local 
vicinity of the thrombus via a simple ‘drip’ infusion approach. Two types of catheters commonly used for 
conventional CDT in the setting of PE treatment are the Cragg-McNamara infusion catheter and the Uni-Fuse 
infusion catheter, though other similar catheters may be used depending on the standard of care at the particular 
clinical facility.  Both these conventional CDT systems are market cleared in the geographies for this study. 
Cragg-McNamara™ Micro Therapeutics Infusion Catheter 
The Cragg-McNamara Micro Therapeutics Infusion Catheter (Fig. 6; Medtronic, Dublin, Ireland) is intended to be 
used for the controlled selective infusion of physician-specified pharmacologic agents or contrast into the general 
vasculature. It comes in 4 and 5 French (F) sizes with a valved-tip, single-lumen catheter designed to be used 
without a guidewire. 
Figure 6 Cragg-McNamara Infusion Catheter 
 
 
Uni-Fuse™  
The Uni-Fuse infusion catheters (Fig. 7; AngioDynamics, Latham, NY) are indicated for the administration of fluids, 
including thrombolytic agents and contrast media in the peripheral and pulmonary artery vasculature. The 
catheter system includes a 4 or 5 F catheter with an occluding ball wire. When inserted into the catheter, the 
occluding ball wire provides force, activating pressure response outlets (slits) and resulting in the consistent 
distribution of thrombolytic agent to an area of thrombus. 
 

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Figure 7 Uni-Fuse Infusion Catheters 
 
Ultrasound-Assisted CDT Catheters 
Ultrasound-assisted thrombolysis (USAT) catheters are a specialized subset of CDT catheters that include miniature 
ultrasound transducers embedded within the distal portion of the catheter. Currently, these specialized catheters 
are available only in the EkoSonic (EKOS™) Endovascular System (Boston Scientific, Marlborough, MA). Like the 
conventional CDT catheters described above, the EKOS catheter is designed to deliver the thrombolytic agent to 
the location of the thrombus; however, in addition, this type of catheter actively emits controlled ultrasonic energy 
to theoretically enhance drug penetration.  The EKOS system is market cleared in the geographies for this study. 
EkoSonic (EKOS™) Endovascular System  
The EKOS Endovascular System (Fig. 8; Boston Scientific, Marlborough, MA) consists of a 5.4 F multi-side-hole 
catheter indicated for ultrasound-facilitated, controlled, and selective infusion of physician-specified fluids, 
including thrombolytics, into the vasculature for the treatment of pulmonary embolism. It is also indicated for the 
infusion of solutions into the pulmonary arteries, and the controlled and selective infusion of physician-specified 
fluids, including thrombolytics, into the peripheral vasculature. The emission of ultrasonic waves is thought to thin 
and separate the fibrin strands to facilitate thrombolytic drug infusion into the thrombus. 
Figure 8 EKOS Endovascular System 
 
 

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3. PRIOR INVESTIGATIONS 
FLOWTRIEVER SYSTEM 
The FlowTriever System was first evaluated for PE treatment in a US pivotal Investigational Device Exemption trial, 
the FlowTriever Pulmonary Embolectomy Clinical Study (FLARE) trial, in subjects with submassive (i.e., 
intermediate-risk) PE. The study was a prospective, multicenter study to evaluate the safety and effectiveness of 
the FlowTriever System in subjects eligible for endovascular treatment of acute PE. This study provided the data 
allowing FDA clearance for the FlowTriever System for use in treatment of PE. 
Following this FDA clearance, a subsequent post-market registry (FlowTriever All-Comer Registry for Patient Safety 
and Hemodynamics (FLASH)) was initiated to continue to evaluate the safety and effectiveness of the FlowTriever 
System for use in the removal of emboli from the pulmonary arteries in a real-world patient population. The all-
comer nature of the registry allows for the evaluation of FlowTriever outcomes in a real-world population including 
both intermediate-risk and high-risk PE patients, and enrollment in the study is ongoing.   
In addition, a second post-market registry (FlowTriever for Acute Massive Pulmonary Embolism (FLAME)) was 
recently initiated. The primary objective of this observational study is to evaluate treatment outcomes of patients 
diagnosed with high-risk (massive) pulmonary embolism who have received treatment with the FlowTriever 
System compared to an established performance goal (literature-based goal). These three Inari-sponsored studies 
(FLARE, FLASH, and FLAME) are summarized below, along with key published literature reporting outcomes from 
FlowTriever use in clinical practice. 
FLARE Study Design and Summary of Results 
FLARE Study Design 
The FLARE study was designed as a US pivotal Investigational Device Exemption trial, in subjects with submassive 
(i.e., intermediate-risk) PE. The study was a prospective, multicenter study to evaluate the safety and effectiveness 
of the FlowTriever System in subjects eligible for endovascular treatment of acute PE. A maximum of 20 study sites 
were planned to participate in the study, and no single study site could enroll more than 25% of the total subjects. 
The study population comprised 106 subjects with acute submassive PE.  
Primary safety and primary effectiveness performance goals were used in the study. To establish the safety 
performance goal, the results from seven studies published in the medical literature in which acute PE patients 
were treated with a heparin control arm were used to develop a composite Major Adverse Event (MAE) rate. MAEs 
were defined when one or more of the following occurred within 48 hours: Device-related death, major bleeding, 
treatment-related clinical deterioration, treatment-related pulmonary vascular injury, or treatment-related cardiac 
injury. Combining these composite MAE rates yielded an estimate of 16% with a 95% confidence interval of 6.7% 
to 25.8% after adjusting for heterogeneity among studies. The safety performance goal was chosen as the upper 
95% confidence limit rounded down to two digits, for a safety performance goal of 25%. 
The variable assessed in the primary effectiveness performance goal was the change in RV/LV ratio from baseline 
to 48 hours. The effectiveness performance goal was based on heparin-treated subjects from four studies 
published in the medical literature in which heparin was a control to an active pharmaceutical drug. Combining 
these results in a meta-analysis yielded a mean RV/LV ratio change from baseline of 12% with 95% confidence 
limits of 4% to 21% after adjusting for heterogeneity among studies. An effectiveness performance goal of 12% 
was selected. 
Subjects were followed for 30 days post-procedure with computed tomography pulmonary angiography (CTPA) at 
48 hours and assessment of Adverse Events (AEs) through 30 days. The primary safety endpoint was assessed from 

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the 48-hour MAE rate and the primary effectiveness endpoint from the change in RV/LV ratio between the 
baseline and 48-hour CTPA imaging studies. Powering considerations for detecting results exceeding the 
established performance goals led to a final sample size of 106 enrolled subjects. 
FLARE Study Results 
In all, 106 subjects were enrolled and treated with the FlowTriever System in FLARE, and 104 of these did not 
receive thrombolytics. Among these, 101 had evaluable CTPA studies suitable for the primary effectiveness 
endpoint. There were also 101 subjects that had 48-hour data suitable for the primary safety endpoint. The mean 
baseline RV/LV ratio was 1.5 ± 0.4, and the mean 48-hour RV/LV ratio was 1.2 ± 0.3. Three subjects had missing 
values for the primary effectiveness endpoint at the 48-hour visit resulting in 101 subjects with both a pre- and 
post-treatment RV/LV ratio for comparison. For these paired subjects, the mean change (reduction) in RV/LV ratio 
from pre- to post-treatment was 0.38 ± 0.3, with a range from an increase of 0.4 to a decrease of 1.4. This mean 
change in RV/LV ratio was 0.38 (25.1%, P < 0.0001), indicating that the null hypothesis was rejected and the 
FlowTriever System met the performance goal.b 
For the primary safety endpoint, 4 subjects (3.8%) in the modified intention to treat population (all subjects with 
treatment attempted and no thrombolytics administered) experienced one or more MAEs. The composite 
endpoint of 3.8% was statistically lower than the performance goal of 25% (P < 0.0001), with an upper one-sided 
95% confidence limit of 8.6%. None of the MAEs reported were device related.57 
In summary, the FLARE trial met its primary safety and effectiveness endpoints. This trial was the basis for the US 
FDA 510(k) clearance of the FlowTriever System for PE treatment in May 2018. 
  FLASH Study Design, Status, and Results 
FLASH Study Design 
The primary study objective of FLASH is to evaluate the safety and effectiveness of the next-generation 
FlowTriever System for use in the removal of emboli from the pulmonary arteries in the treatment of acute 
pulmonary embolism (PE). The use of the device is being assessed in a real-world population, with eligibility criteria 
that closely approximate its use in clinical practice. 
The FLASH Study is a prospective, single-arm, multicenter all-comer registry of the FlowTriever System for 
intermediate-risk (submassive) and high-risk (massive) PE.  While originally designed to enroll up to 500 subjects at 
up to 50 registry sites in the United States, the study has been expanded to enroll up to 1,000 subjects treated 
with FlowTriever, including up to 800 subjects in up to 70 US sites and up to 200 in up to 30 Europe sites. The study 
will also include an additional 300 subjects with anticoagulation treatment as the initial planned primary treatment 
strategy for intermediate-risk PE.  Enrollment in the FLASH registry is ongoing. 
The primary endpoint is the rate of Major Adverse Events (MAE). MAEs are defined as a composite, when one or 
more of the following events occur: 
• 
Device-related mortality through 48 hours after the index procedure, or 
• 
Major bleeding through 48 hours after the index procedure, or 
• 
Intra-procedural device or procedure-related adverse events, including: 
o 
Clinic deterioration defined by hemodynamic or respiratory worsening, or 
 
b The p-value is from a one-sided t-test (Wald statistic) from the multiple imputation analysis, testing the null hypothesis that the mean change 
is not greater than the performance goal of 0.12.  

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o 
Device-related pulmonary vascular injury, or 
o 
Device-related cardiac injury 
Secondary safety endpoints include individual components of the MAE composite endpoint, major access-site 
complications requiring open surgical or endovascular intervention or blood transfusion, all-cause mortality 
through 30 days, and device-related serious adverse events within 30 days. Secondary effectiveness endpoints 
include reduction in pulmonary artery pressure (PAP) and other hemodynamic improvements during the 
procedure, and reduction in RV/LV ratio from baseline to 30 days and 6 months. 
FLASH Interim Results 
An interim analysis of outcomes out to 30 days on the first 230 subjects was presented at the 2021 Society for 
Interventional Radiology Annual Conference in March, 2021, with the abstract from this conference published in 
the Journal of Vascular and Interventional Radiology, as well as earlier conferences.58-60 These subjects (60.7 ± 13.9 
years, 52.2% male) were enrolled across 17 sites, with 93.0% having intermediate-risk PE and 7.0% high-risk PE. 
The average baseline RV/LV ratio was 1.6 ± 0.5 and sPESI was 1.6 ± 1.1. 96.3% of subjects had elevated biomarkers, 
and 69.7% of subjects had concomitant DVT. The primary endpoint of composite MAEs occurred in three (1.3%) 
subjects, all of which were non-ICH major bleeds, and no deaths occurred within 48 hours.  
In-hospital outcomes demonstrated significant improvements across several acute parameters. Subjects 
experienced significant on-table hemodynamic improvements, including a 21.9% decrease in mean pulmonary 
artery pressure (32.0 mmHg to 25.0 mmHg, P < 0.0001) and a 20.1% decrease in heart rate (pre-procedural high of 
113.2 bpm to 90.5 bpm immediately post-procedure, P < 0.0001). There was only one (0.4%) access site 
complication. The median post-procedure hospital length of stay was 3.0 [2.0 – 5.1] days and ICU length of stay 
was 0.0 [0.0 – 1.1] days.  
30-day follow up data was available for 201 subjects in this analysis. In this population, there was one death (0.5% 
mortality), which was unrelated to the device, and there were ten hospital readmissions, one of which was related 
to the procedure. The average RV/LV ratio improved by 33.2% at a median follow up of 30 days (P < 0.0001) and 
subjects with confirmed baseline dyspnea had a significant improvement from baseline to 30 days (Modified 
Medical Research Council Dyspnea Scale, 3.0 ± 1.0 to 1.4 ± 1.3, P < 0.0001). 
These results of the FLASH all-comer registry demonstrate both safety and efficacy of the FlowTriever System, with 
a low all-cause mortality rate (0.0% at 48 hours, 0.5% at 30 days; no device-related deaths), along with significant 
and immediate hemodynamic improvements and continued improvements in RV/LV ratio and dyspnea out to 30 
days. 
FLAME Study Design and Status 
The primary study objective of FLAME is to evaluate treatment outcomes of subjects diagnosed with high-risk 
(massive) pulmonary embolism who have received treatment with the FlowTriever System compared to an 
established performance goal (literature-based goal). In addition to the primary objective, outcomes of subjects 
diagnosed with high-risk (massive) pulmonary embolism who have received treatment with other (non-
FlowTriever) therapies will also be analyzed.  It is expected that 250 subjects will be enrolled across all therapies 
utilized in the study.  The study will be conducted at up to 20 US sites. 
The primary endpoint of this study will be an in-hospital composite endpoint of:  
• 
All-cause mortality  
• 
Bailout to an alternative thrombus removal strategy  
• 
Clinical deterioration  

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• 
Major bleeding 
Additional secondary endpoints and utility measures will be collected and analyzed as well.  Safety events will be 
adjudicated by an external Clinical Events Committee (CEC).  
Enrollment is currently ongoing, and no interim data have been reported to date. 
 Additional Published Results 
Several analyses of FlowTriever outcomes from single-center clinical experiences have been published for PE 
patients who are not part of the FLASH registry.61-63 Toma, et al., reported results from a multicenter retrospective 
analysis of 34 high-risk or very sick submassive PE patients, demonstrating significant improvements in cardiac 
index and mean pulmonary artery pressure, with low procedural failure rate (2/34, 5.9%) and low mortality (1/34, 
2.9%).62 A more recent single-center retrospective analysis from Buckley and Wible compared outcomes in 
intermediate-high and high-risk PE patients treated with FlowTriever to those who receive routine care (AC alone, 
AC + CDT, or systemic thrombolysis). Results demonstrate significantly lower in-hospital mortality (3.6% vs 23.3%, 
P < 0.001) and length of hospital stay (2.1 ± 1.2 days vs 6.1 ± 8.6 days, P < 0.001) for FlowTriever patients than 
those receiving routine care.64  Additional single-center retrospective studies demonstrate similar results, with 0% 
mortality and 0-4% major complicate rate, as well as significant improvements in acute hemodynamic 
measurements.61, 63 FlowTriever System has also recently been used to effectively remove thrombus from 
intermediate- to high-risk PE patients experiencing a “thrombotic storm”-like response to COVID-19.65 Taken 
together with the data from FLARE and FLASH, these data demonstrate the safe and effective treatment of 
intermediate- and high-risk PE patients, even for those patients contraindicated to thrombolysis, with the 
FlowTriever System. Comparative data assessing these outcomes in a randomized trial including other advanced 
therapies is still lacking and will be the focus of this study. 
CATHETER-DIRECTED THROMBOLYSIS 
Conventional Catheter-Directed Thrombolysis (CDT) 
Due to the elevated bleeding risk noted with systemic thrombolysis, the use of CDT to deliver thrombolytics locally 
rather than systemically has increased. While many mostly retrospective studies have been published on CDT 
outcomes, randomized studies comparing systemic to catheter-directed thrombolytics administration have been 
lacking. To address this, Kuo, et al., published a systematic review and meta-analysis comparing the two treatment 
options using data collected from 594 patients across 35 studies.42 Results demonstrate an 86.5% clinical success 
rate, with minor and major procedural complications of 7.9% and 2.4%, respectively, which compared favorably to 
the 22% major bleeding rate published in the ICOPER study for systemic thrombolysis.66 
Avgerinos, et al., published a retrospective review of patients receiving CDT versus AC alone.43 While RV/LV ratios 
showed a non-significant trend towards greater improvement in the CDT group, these patients still experienced 
significantly higher bleeding complications than those on AC alone (4 vs 3 major bleeds, and 7 vs 0 minor bleeds for 
CDT and AC (P = 0.028), respectively). A propensity-matched retrospective analysis of data from the National 
Readmission Database compared outcomes of patients treated with CDT and systemic thrombolysis, with CDT 
patients matched 2:1 with systemic thrombolysis patients (N=4,426). Results demonstrate significantly lower in-
hospital mortality (6.1% vs 14.9%, P <0.001) and a lower composite measurement of mortality + gastrointestinal 
bleeding + intracranial hemorrhage in the CDT group (8.4% vs 18.3%, P < 0.001). 
Ultrasound-assisted Catheter-Directed Thrombolysis (USAT) 
USAT using the EkoSonic catheter system (EKOS) incorporates ultrasonic pulses, along with thrombolytic infusion, 
to purportedly accelerate the lytic process by thinning and separating the fibrin strands. This device has the most 
published clinical evidence of the advanced therapies available for PE, with several retrospective studies,67-70 as 

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well as randomized controlled studies comparing EKOS outcomes to AC alone45 or to CDT.49 Two seminal 
multicenter, prospective studies, ULTIMA45 and SEATTLE-II46, evaluated the ultrasound-assisted thrombolysis 
(USAT) approach for submassive and massive PE.  
The ULTIMA study compared EKOS to AC (heparin) alone in a total of 59 intermediate-risk PE patients across eight 
centers in Switzerland and Germany.45 Results demonstrated a significantly greater reduction in RV/LV ratio, along 
with other echocardiographic right heart parameters, at 24 hours in EKOS patients compared to those treated with 
heparin. However, any significant difference in RV/LV ratios between EKOS and heparin was absent at 90 days.45 
There was no device-related mortality or major bleeding events related to either study treatment, but minor 
bleeding complications were observed in 10% and 3% of patients in the USAT and CDT arms, respectively (P=0.61). 
The SEATTLE II study was a single-arm prospective study of 150 submassive and massive PE patients to further 
evaluate the safety and efficacy of EKOS, with a primary efficacy outcome of the change in RV/LV ratio within 48 
hours of procedure initiation, and a primary safety outcome of major bleeding within 72 hours of procedure 
initiation. One hundred fifty submassive and massive PE patients each received 24mg of tPA, infused either in one 
catheter over 24hr, or in two catheters over 12 hours. Results demonstrated statistically significant improvements 
in RV/LV ratio, mean PAP, and thrombus burden as defined by the modified Miller Index score at 48 hours. One 
severe bleed and 16 moderate bleeding events in 15 patients (10%) occurred out to 72 hours.46 Further refinement 
of the lytic dose and infusion duration using EKOS was conducted in the OPTALYSE PE trial, a multicenter, 
prospective study with 101 intermediate-risk PE patients randomized to 1 of 4 study arms in which both tPA dose 
and infusion duration were varied.47 It is notable that randomization and enrollment into the study arm using 
12mg (unilateral)-24mg (bilateral) of tPA over 6 hours was stopped after an ICH developed that was considered 
probably related to thrombolytic therapy and anticoagulation by the safety monitor. Results indicated that lower-
dose tPA (as low as 4 mg per lung) and infusion duration as low as 2 hours was as effective as 6mg or 12mg doses 
infused up to 6 hours. 
Taken together, these studies demonstrate that USAT is effective relative to AC, and like conventional CDT, the 
local delivery of smaller doses of thrombolytics compared to systemic administration likely provides greater 
patient safety. However, the question remained whether the ultrasound technology provided significant 
improvement over conventional CDT. To address this, Tafur, et al., performed a systematic review and meta-
analysis of 23 studies and 700 subjects to summarize the evidence on safety and efficacy for conventional CDT 
versus USAT.49 Of the included studies, 18 evaluated CDT only, 6 evaluated USAT only, and only one study 
evaluated and compared both treatments. The meta-analysis found no difference in the rate of bleeding 
complications between USAT and conventional catheter-directed thrombolysis, (total bleeding: 12% USAT vs. 10% 
CDT; major bleeding: 4% USAT vs. 10% CDT).48 The review, however, documented a trend toward improved 
survival with USAT; 4% vs. 9% mortality in the USAT and conventional CDT subjects, respectively. However, the 
methods used to evaluate efficacy varied amongst studies, preventing a pooled comparative analysis. The authors 
conclude, however, that while the bleeding risk appeared to be lower with USAT treatments, the heterogeneity of 
the studies and lack of comparative data prevented them from reaching a definitive conclusion. They point out 
that the calculated mortality rates (4% for USAT and 9% for CDT) highlight the continued critical need for further 
study in this area.  
Results from a more recent prospective, randomized control trial (SUNSET sPE) comparing USAT to CDT were 
recently published.49 Eighty-one submassive PE patients from three clinical US centers were randomized 1:1 to 
either USAT or CDT and followed up out to 90 days. Primary efficacy outcomes of reductions in both pulmonary 
obstruction index and score were not different between the two groups. The reduction in RV/LV ratio from pre-
procedure to 48 hours was statistically greater in the CDT group (USAT: 0.37 ± 0.34; CDT: 0.59 ± 0.42; P=0.01), and 
the overall mean hospital stay was shorter in the CDT arm as well (USAT: 4.1 ± 8.8 days; CDT: 2.4 ± 1.2 days; 
P=0.03). Two major and three minor bleeding events and one in-hospital death were recorded, all in the USAT 
group. The conclusion of this publication is that USAT may not confer a benefit over CDT.49 

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EKOS is being further evaluated for safety and efficacy in the largest PE device registry to date, KNOCOUT, with 
1,500 patients enrolled and a 1-year follow up planned.71 No data has been published to date from this study. In 
addition, the recently-initiated HI-PEITHO study is a randomized controlled trial comparing EKOS to standard AC 
with a planned enrollment of 406 intermediate high-risk PE patients.72  
4. STUDY OBJECTIVE 
The primary study objective is to compare the clinical outcomes of patients treated with the FlowTriever System 
versus Catheter-Directed Thrombolysis (CDT) for use in the treatment of acute pulmonary embolism (PE). 
5. OUTCOME VARIABLES 
PRIMARY ENDPOINT DEFINITION  
The primary endpoint is a composite clinical endpoint constructed as a win ratio, a hierarchy of the following, 
which are assessed at hospital discharge or at 7 days after the index procedure, whichever is sooner: 
1. All-cause mortality, or 
2. Intracranial hemorrhage (ICH), or 
3. Major bleeding per ISTH definition4, or  
4. Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout 
therapy, or 
5. ICU admission and ICU length-of-stay during the index hospitalization and following the index procedure. 
Definition of Intracranial Hemorrhage 
Intracranial hemorrhage (ICH) is defined as ANY bleeding involving the brain parenchyma, ventricular system, or 
subarachnoid, subdural, or epidural regions, as identified by CT scan or MRI, regardless of symptoms.  
Definition of Major Bleeding 
Major bleeding is defined according to the International Society for Thrombosis and Haemostasis (ISTH) definition 
of major bleeding in non-surgical subjects4.  
1. Fatal bleeding, and/or 
2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, 
retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or 
3. Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of 
two or more units of whole blood or red cells.  
Definitions of Clinical Deterioration and Bailout 
Clinical deterioration is defined as documented objective hemodynamic or respiratory worsening that is new (i.e. 
not present at the time of enrollment).   
Clinical deterioration is when one or more of the following is definitively documented, with relation to both the 
severity and the duration of the event: 
• 
Hypotension with systolic blood pressure <90 mm Hg lasting at least 30 minutes, unresponsive to fluid 
resuscitation, and requiring the addition of or increased dose of vasopressors 

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• 
Fall in systolic blood pressure by 40 mm Hg or more, lasting at least 30 minutes, and accompanied end-
organ hypoperfusion (such as oliguria, mental status changes, ischemic extremities) 
• 
Cardiac arrest requiring cardiopulmonary resuscitation 
• 
Bradycardia lasting more than 10 minutes, accompanied by hypotension, and requiring pharmacologic 
intervention or insertion of a pacemaker 
• 
Ventricular tachycardia or fibrillation requiring pharmacologic intervention or defibrillation 
• 
Requirement for an increase in fraction of inspired oxygen requirements 0.20 or greater, lasting longer 
than 30 minutes (e.g. from 0.21 to 0.41) 
• 
Need for intubation in a previously non-intubated subject, or unplanned use of extracorporeal membrane 
oxygenation (ECMO) 
Note that transient fluctuations in hemodynamic and/or respiratory function may be common during 
thrombectomy and thrombolysis procedures, and events not meeting both severity and duration requirements are 
not considered meeting the definition of Clinical Deterioration.  Such changes may resolve spontaneously upon 
continuation of an existing treatment plan, and as such are unremarkable.  Vagal episodes are also, in themselves, 
not considered Clinical Deterioration.  Shorter term changes in hemodynamic or respiratory function, when 
accompanied by an unplanned escalation of therapeutic measures under the primary clinician’s judgement to 
avoid overt deterioration, may be considered Bailout Therapy.  Any such escalations of therapy will be 
documented in detail and adjudicated by a Clinical Events Committee (CEC). 
Bailout Therapy is an unplanned escalation of therapeutic measures, taken when the patient’s condition has not 
improved or is not improving according to expectations.  Potential Bailout Therapy events will be adjudicated by a 
Clinical Events Committee, including when any of the following occur: 
• 
Unplanned use of additional mechanical, pharmacomechanical, pharmacologic catheter-based therapies, 
or systemic thrombolytics, or changing from the assigned treatment strategy, after initial treatment 
strategy as assigned was initiated. 
o 
If catheter-directed thrombolysis (CDT) was the assigned treatment strategy and 
emergent/clinically driven systemic thrombolytic administration (e.g. ≥ 10 mg tPA) was required 
after CDT was initiated, this would be considered a bailout.  
 
If the length of thrombolytic administration is simply extended and is not emergent or 
clinically driven, this would not qualify as a bailout.   
o 
If mechanical thrombectomy was the assigned treatment strategy, low-dose catheter-directed 
adjunctive thrombolytic therapy (less than 10 mg tPA) that is administered intra-procedurally or 
post-procedurally will be strongly discouraged but not considered a bailout 
• 
Surgical thrombectomy 
Before escalating to a Bailout Therapy, physicians are encouraged to consider the patient’s condition and identify 
one or more reasons from the following list to justify the need for Bailout Therapy.  These reason(s) will be 
documented in the study case report forms (CRFs).  
• 
Persistent elevated respiratory rate 
• 
Ongoing or increased requirement for supplemental oxygen 
• 
Persistent or new-onset tachycardia 
• 
Sustained or sudden bradycardia 
• 
Sudden or persistent hypotension, not associated with a vagal episode, or signs of end-organ 
hypoperfusion 
• 
Hemodynamic worsening or lack of hemodynamic improvement 
• 
Lack of improved lung perfusion, or inadequate clot resolution 
• 
New-onset, persistent, or worsening symptoms of PE 

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Any unplanned escalation of therapy adjudicated by the CEC to not meet clinical definitions for Bailout Therapies 
will be considered a protocol deviation.  
Definition of ICU Admission and ICU Length of Stay 
ICU Admission will be defined as admission or transfer to an Intensive Care Unit (ICU), Critical Care Unit (CCU), or 
similar high-acuity floor, collectively referred to as “ICU.”  For the purpose of the endpoint assessment, ICU 
Admission is met under the following conditions: 
• 
Orders are entered for Subject to be admitted or transferred to the ICU after the end of the Index 
Procedure and before hospital discharge from the index hospitalization, up to a maximum of 7 days from 
the end of the Index Procedure, or 
• 
Subject had been in the ICU leading up to the Index Procedure, with plans to return to the ICU 
immediately after the end of the Index Procedure, with or without a transfer to a PACU, recovery room, 
or similar temporary step-down unit according to local standard.  
ICU Length of Stay (LOS) is the total number of hours a subject is medically required to be in the ICU, measured 
from the end of the Index Procedure or the time of ICU Admission, whichever is later, until the time of an order to 
discharge the subject from the ICU or transfer the subject to a standard or lower-acuity unit.  If a subject remains 
physically located in the ICU due to hospital bed availability, transport delays, or other non-medical reasons 
instead of a need for high acuity of care, the time of the order for discharge or transfer, rather than the actual time 
a subject physically leaves the ICU, is used for assessing ICU LOS.  
For subjects getting discharged from or transferred off the ICU and returning again during the index 
hospitalization, up to a maximum of 7 days after the Index Procedure, the total hours of all ICU admissions or 
transfers during that period (i.e., after the Index Procedure and until hospital discharge up to a maximum of 7 
days) are used for assessing ICU LOS. 
Subjects who had been in the ICU leading up to the Index Procedure, but not returning to the ICU after the end of 
the Index Procedure, are not considered to have had an ICU Admission per the endpoint definition. 
For the win ratio primary endpoint, ICU admission and ICU LOS are characterized hierarchically as follows: 
1. No ICU Admission 
2. ICU Admission, lasting between 0 – 24 hours 
3. ICU Admission, lasting longer than 24 hours 
SECONDARY ENDPOINTS  
The secondary endpoints of the study will assess safety, effectiveness, and utility measures, as follows: 
• 
Composite clinical endpoint constructed as a win ratio hierarchy of the following four components, 
assessed at hospital discharge or at 7 days after the index procedure, whichever is sooner: 
o 
All-cause mortality, or 
o 
Intracranial hemorrhage (ICH), or 
o 
Major bleeding per ISTH definition4, or  
o 
Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a 
bailout therapy 
• 
Individual components of the win ratio composite endpoint, assessed at hospital discharge or at 7 days 
after the index procedure, whichever is sooner: 
o 
All-cause mortality 
o 
Intracranial hemorrhage (ICH) 

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o 
Major bleeding per ISTH4 definition 
o 
Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a 
bailout therapy 
o 
ICU admission and ICU length of stay during the index hospitalization and following the index 
procedure 
• 
All-cause mortality within 30 days from index procedure 
• 
PE-related and all-cause readmission within 30 days from index procedure 
• 
Device and drug-related serious adverse events through the 30 day visit 
• 
Clinically Relevant Non-Major (CRNM) and Minor bleeding events through hospital discharge or at 7 days 
after the index procedure, whichever is sooner 
• 
Change in right-ventricular/left-ventricular (RV/LV) ratio from baseline to 24 hour visit, as measured by 
echocardiography or CT 
• 
mMRC Dyspnea score at 24 hour visit and 30 day visit 
• 
Length of total hospital stay and post-index-procedure hospital stay (to a maximum of 30 days) 
• 
Disease-specific and general health-related quality of life at the 30 day visit (PEmb-QoL and EQ-5D-5L) 
6. STUDY DESIGN 
This study is a prospective, multicenter, randomized controlled trial of the FlowTriever System compared to CDT 
for acute PE, and includes a non-randomized cohort for subjects with an absolute contraindication to 
thrombolytics. The study will collect data on demographics, comorbidities, details from the PE diagnosis and 
treatment, and clinical outcomes through 30-day follow up. 
Randomized Controlled Trial Cohort (RCT Cohort): 
This study is a prospective, multicenter, randomized controlled trial of the FlowTriever System compared to 
Catheter-Directed Thrombolysis (CDT) for treatment of acute PE. 
Non-Randomized Absolute Contraindication to Thrombolytics Cohort (Contraindication Cohort): 
Subjects who meet study eligibility criteria and who have an absolute contraindication to thrombolytics, whose 
initial planned primary treatment strategy includes FlowTriever, will be evaluated as part of the Contraindication 
Cohort.  The same RCT Cohort clinical assessments and follow up schedule will be administered in this 
Contraindication Cohort. 
STUDY POPULATION 
RCT Cohort: Up to 550 subjects with acute PE will be enrolled and randomized at up to 60 study sites. All subjects 
who sign informed consent and who meet all of the inclusion criteria and none of the exclusion criteria will be 
randomized (1:1, FlowTriever or CDT).  
• 
One-to-one (1:1) randomization will be stratified by bleeding risk, as measured by the VTE-BLEED score3.     
 
 
 
 

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Table 1 VTE-BLEED Algorithm 
Parameter 
Points 
Active cancer 
2 
Male patient with uncontrolled hypertension (≥140 mmHg) 
1 
Anemia 
1.5 
History of bleeding 
1.5 
Renal dysfunction (Cr clearance 30-60 ml/min) 
1.5 
Age ≥60 years 
1.5 
TOTAL 
≥2 indicates higher risk of bleeding on stable AC vs <2 
9 
 
• 
Stratification by the VTE-BLEED algorithm will occur automatically in the Electronic Data Capture (EDC) 
system upon data entry, and randomization will be assigned accordingly.  
Contraindication Cohort: Up to 150 additional subjects who meet study eligibility criteria and who have an 
absolute contraindication to thrombolytics, whose initial planned primary treatment strategy includes FlowTriever, 
will be evaluated as part of the Contraindication Cohort.  The same RCT Cohort clinical assessments and follow up 
schedule will be administered in this Contraindication Cohort. 
POINT OF ENROLLMENT  
To participate in the study, the patient must sign the informed consent.  If a subject signs the informed consent but 
is later deemed NOT to meet the invasive systolic PA pressure eligibility criteria, the subject would be considered a 
screen failure and not enrolled in either the RCT Cohort or the Contraindication Cohort.  Screen failures will be 
tracked in the EDC system with rationale for the screen failure.  The point of enrollment is when the subject meets 
all eligibility criteria and study device enters the subject’s body.   
Enrollment considerations in study design 
Any patient with a documented absolute contraindication to thrombolytics will be excluded from the RCT Cohort 
but may be enrolled in the Contraindication Cohort if treated with FlowTriever.  Absolute contraindications include 
(per ESC Guidelines 20191 and AHA Scientific Statements 2019): 
• 
History of hemorrhagic stroke or stroke of unknown origin 
• 
Ischemic stroke in previous 6 months 
• 
Presence of intracranial conditions that may increase the risk of bleeding, such as neoplasms, 
arteriovenous malformations, or aneurysms  
• 
Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma  
• 
Bleeding diathesis 
• 
Active internal bleeding, excluding menses  
• 
Aortic dissection 

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• 
Severe uncontrolled hypertension 
• 
Any other condition listed as an absolute contraindication on the product label for the thrombolytic agent 
planned for use by local standard and investigator discretion 
Subjects with a relative contraindication to thrombolytics are eligible for the RCT Cohort per protocol. Subjects 
with only relative contraindication(s) to thrombolytics are not eligible for the Contraindication Cohort. Relative 
contraindications include: 
• 
Transient ischemic attack in previous 6 months 
• 
Oral anticoagulation, except for aspirin 
• 
Therapeutic LMWH within 24 hours 
• 
Pregnancy or first post-partum week 
• 
Non-compressible puncture sites 
• 
Traumatic resuscitation, defined as prolonged (>10 min) cardiopulmonary resuscitation 
• 
Refractory hypertension (systolic BP >180 mmHg or diastolic BP >110 mmHg) on two confirmed 
measurements 
• 
Advanced liver disease 
• 
Infective endocarditis 
• 
Active peptic ulcer  
• 
Recent administration of glycoprotein (GP) IIb/IIIa inhibitors 
• 
Anemia (e.g. hemoglobin <10 g/dL) 
Figure 9 Subject Enrollment Flowchart 
 

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INCLUSION CRITERIA  
Subjects must meet each of the following criteria to be included in the study: 
1. Age ≥ 18 years 
2. Echo, computed tomographic pulmonary angiography (CTPA), or pulmonary angiographic evidence of any 
proximal filling defect in at least one main or lobar pulmonary artery 
3. Including ALL of the following: 
a. Clinical signs and symptoms consistent with acute PE, or PESI class III-V, or sPESI ≥1 
AND 
b. Hemodynamically stable 
AND 
c. 
RV dysfunction on echocardiography or CT 
AND 
d. Any one or more of the following present at the time of diagnosis:  
i. Elevated cardiac troponin levels 
ii. History of heart failure 
iii. History of chronic lung disease 
iv. Heart rate ≥110 beats per minute 
v. SBP <100mmHg  
vi. Respiratory rate ≥30 breaths per minute 
vii. O2 saturation <90% 
viii. Syncope related to PE 
ix. Elevated lactate 
4. Intervention planned to begin within 72 hours of the later of either  
a. Confirmed PE diagnosis 
OR 
b. If transferring from another hospital, arrival at the treating hospital 
5. Symptom onset within 14 days of confirmed PE diagnosis 
EXCLUSION CRITERIA  
Subjects will be excluded from the study for any of the following criteria:  
1. Unable to anticoagulate with heparin, enoxaparin or other parenteral antithrombin 
2. Index presentation with hemodynamic instability that are part of the high-risk PE definition in the ESC 
Guidelines 20191, including ANY of the following: 
a. Cardiac arrest 
OR 
b. Systolic BP < 90 mmHg or vasopressors required to achieve a BP ≥90 mmHg despite adequate 
filling status, AND end-organ hypoperfusion 
OR 
c. 
Systolic BP < 90 mmHg or systolic BP drop ≥40 mmHg, lasting longer than 15 min and not caused 
by new-onset arrhythmia, hypovolemia, or sepsis 
3. Known sensitivity to radiographic contrast agents that, in the Investigator’s opinion, cannot be adequately 
pre-treated 
4. Imaging evidence or other evidence that suggests, in the opinion of the Investigator, the patient is not 
appropriate for catheter-based intervention (e.g., inability to navigate to target location, clot limited to 
segmental/subsegmental distribution, predominately chronic clot)  
5. Patient has right heart clot in transit identified at baseline screening 
6. Life expectancy < 30 days (e.g., stage 4 cancer or severe COVID-19 infection), as determined by the 
Investigator 

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7. Current participation in another drug or device study that, in the investigator’s opinion, would interfere 
with participation in this study 
8. Current or history of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic 
thromboembolic disease (CTED) diagnosis, per ESC 2019 guidelines1  
9. Invasive systolic PA pressure ≥70mmHg prior to study device entering the body 
10. Administration of bolus or drip/infusion thrombolytic therapy or mechanical thrombectomy for the index 
PE event within 48 hours prior to enrollment   
11. Ventricular arrhythmias refractory to treatment at the time of enrollment 
12. Known to have heparin-induced thrombocytopenia (HIT) 
13. Subject has any condition for which, in the opinion of the investigator, participation would not be in the 
best interest of the subject (e.g., compromise the well-being or that could prevent, limit, or confound the 
protocol-specified assessments). This includes a contraindication to use of FlowTriever or CDT System (for 
example, EKOS System) per local approved labeling 
14. Subject has previously completed or withdrawn from this study 
15. Patient unwilling or unable to conduct the follow up visits per protocol. 
7. ASSESSMENTS AND FOLLOW UP SCHEDULE  
SCHEDULE OF ASSESSMENTS 
The schedule of assessments comprises the assessments to be performed for all subjects enrolled in the study.  
Any departures from the follow up schedule will be documented as protocol deviations.  
 
 

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Schedule of Assessments  
Assessment 
Baseline 
(≤ 72 hrs)a 
 
Index Procedureh 
(Day 0) 
24 Hour Visit 
(24 hrs. ± 8 hrs.) 
Hospital 
Discharge e 
30 Day Visit 
(30 days + 15 
days) 
Unscheduled 
Visit 
Informed Consent  
X 
 
 
 
 
 
Inclusion/exclusion review 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical history, risk factors, and PE condition 
X 
 
 
 
 
 
Anticoagulation regimen 
X 
X 
X 
X 
X 
X 
Clinical labs (Hemoglobin, Troponin) 
X 
 
 
 
 
 
Clinical labs (Hemoglobin, ACT, and PTT) 
 
X 
 
 
 
 
Imaging (Echo or CT)f 
X 
 
X 
 
 
 
mMRC dyspnea score, Borg, and NYHA  
X 
 
X 
X 
X 
 
Oxygenation status 
 
X d 
X 
X 
X 
 
Invasive PA pressures (required Pre-Index 
Procedure) 
 
X b 
 
 
 
 
Invasive PA pressures (optional Post-Index 
Procedure) 
 
X c 
 
 
 
 
Bleeding measures 
 
X 
X 
X 
 
 
Evaluation of primary endpoint componentsg 
 
 
 
X 
 
 
PEmb-QoL and EQ-5D-5L  
 
 
 
 
X 
 
Adverse event assessment 
 
X 
X 
X 
X 
X 
a Baseline assessment must be done ≤ 72 hours of Index Procedure  
b Interventionalists will collect pulmonary artery pressures immediately before primary therapeutic catheter insertion.   
c Trained interventionalists will collect pulmonary artery pressures at least 10 minutes after primary therapeutic catheter (for CDT) begins therapy, or after the 
primary therapeutic catheter (for FlowTriever) is removed for the last time.  Additional PA pressures are requested to be collected in the CDT subjects 6 hours 
(± 2 hours) post procedure using the same technique.  
d Collect oxygenation status just prior to index procedure 
e Note that the Discharge Visit can be done at the same time as the 24-hour visit if applicable.  However, if both visits are completed at the same time, both 
CRFs will need to be filled out.  There are no windows from Index Procedure determining when the Discharge Visit must be completed.  The Discharge Visit is 
completed when the patient is discharged from the hospital and the assessments are completed within the 12 hours prior to discharge.  If the subject has not 
been discharged from the hospital by the 30-day visit, then the Discharge Visit is missed and the 30-day assessment (including evaluation of primary endpoint 
components) and patient exit is completed. 
f Imaging can be either echo or CT, but needs to be the same modality within each patient at Baseline and 24-hour visit 
g Note that the evaluation of endpoint considerations include All-cause mortality, ICH, Major bleeding, Clinical deterioration and/or escalation to a bailout 
therapy, and ICU admission and ICU length-of-stay.  These are assessed at hospital discharge or 7 days after the index procedure, whichever is earlier.  If a 
subject is still in the hospital and exits the study for any reason before the 30-day Visit, evaluation of primary endpoint components should be completed at 
the time of patient exit. 
h The Index Procedure begins when access for treatment is obtained.  The Index Procedure is considered complete upon exit from the procedure room.  The 
time of exit from the procedure room is the time reference used for the subsequent visit windows including the 24-hour visit. 
 
 

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BASELINE ASSESSMENTS 
The baseline assessments must be done ≤ 72 hours of Index Procedure including: 
• 
Informed consent 
• 
Inclusion/exclusion review 
• 
Demographics 
• 
Medical history, risk factors, and PE condition 
• 
Anticoagulation regimen 
• 
Clinical labs (Hemoglobin, Troponin) 
• 
Cardiac imaging (Echo or CT) 
o 
Imaging can be either echo or CT, but needs to be the same modality within each patient at 
baseline and 24-hour visit. 
• 
mMRC dyspnea score, Borg, and NYHA 
ALLOCATION AND RANDOMIZATION 
Upon the patient meeting baseline eligibility criteria and providing informed consent, a check against the list of 
absolute contraindications to thrombolytics is performed (see Figure 9: Patient Enrollment Flowchart).  Subjects 
with one or more absolute contraindications to thrombolytics and whose initial treatment plan includes 
FlowTriever are allocated to the Contraindication Cohort.  Subjects without any absolute contraindications 
(whether there are relative contraindications to thrombolytics or no contraindication to thrombolytics) are 
allocated to the RCT Cohort.   
Study sites will receive the subject randomization assignment electronically in the electronic data capture (EDC) 
system upon completion of baseline information used to stratify randomization using the calculated VTE-BLEED 
score.   Subjects will be randomized to and treated with (a) mechanical thrombectomy with FlowTriever or (b) 
catheter-directed thrombolysis per local practice standards. 
INDEX PROCEDURE  
The initial catheter-based intervention for acute PE is considered the Index Procedure.  The procedure is 
conducted under fluoroscopic/angiographic guidance. Refer to the Instructions for Use (IFU) for techniques and 
methods for device deployment. The following assessments are collected during the index procedure including:  
• 
Anticoagulation regimen 
• 
Clinical labs (Hemoglobin, ACT, and PTT collected just prior to index procedure intervention) 
• 
Oxygenation status collected just prior to index procedure 
• 
Invasive PA pressures (required pre-index procedure) 
o 
Interventionalists will collect pulmonary artery pressures immediately before primary 
therapeutic catheter insertion.   
• 
Invasive PA pressures (optional post-index procedure) 
o 
Trained interventionalists will collect pulmonary artery pressures at least 10 minutes after 
primary therapeutic catheter (for CDT) begins therapy, or after the primary therapeutic catheter 
(for FlowTriever) is removed for the last time. Additional PA pressures are requested to be 
collected in the CDT subjects 6 hours (± 2 hours) post procedure using the same technique. 
• 
Bleeding measures 
• 
Adverse event assessment 
The Index Procedure begins when access for treatment is obtained.  The Index Procedure is considered complete 
upon exit from the procedure room.  The time of exit from the procedure room is the time reference used for the 
subsequent visit windows including the 24-hour visit.  The 7-day maximum for in-hospital primary endpoint 

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assessment is defined as 168 hours from the end of the Index Procedure.  The 30-day Visit window refers to 30 
calendar days from the day the Index Procedure ends. 
Recommendations for Anticoagulation Management and Thrombolytic Therapy 
In order to approximate real-world practice, the use of pre-procedure, intra-procedure, and post-procedure 
anticoagulation should be guided by investigator discretion, local standard of care, and in accordance with IFU for 
the assigned therapy.   
Similarly, dose and duration of thrombolytic agents in subjects assigned to CDT is guided by investigator discretion, 
local standard of care, and in accordance with IFU.  Initial dosing strategy should be recorded in the corresponding 
CRF, along with any changes in dose throughout the infusion, including extended infusion times.  Bolus 
thrombolytics that are part of initial treatment plan are not considered bailout, although bolus lytics are 
discouraged in subjects assigned to FlowTriever therapy.   
Suggested PTT target to avoid bleeding during CDT, per SEATTLE-II, is PTT 40-60s. 
FOLLOW UP ASSESSMENTS 
Follow up evaluations will include the 24-hour visit (24 hrs ±8 hrs), hospital discharge, and the 30-day visit (30 days 
+15 days).  All windows reference time from Index Procedure completion (defined as time of exit from the 
procedure room).   
24-hour visit:  The following assessments will be performed at the 24-hour visit: 
• 
Anticoagulation regimen 
• 
Cardiac imaging (Echo or CT required) 
o 
Imaging can be either echo or CT, but needs to be the same modality within each patient at baseline 
and 24-hour visit. 
• 
Oxygenation status 
• 
mMRC dyspnea score, Borg, and NYHA 
• 
Bleeding measures 
• 
Adverse event assessment 
Note that the discharge visit can be done at the same time as the 24-hour visit if applicable.  However, if both visits 
are completed at the same time, both CRFs will need to be filled out. 
Discharge visit:  The following assessments will be performed at the discharge visit: 
• 
Anticoagulation regimen 
• 
mMRC dyspnea score, Borg, and NYHA 
• 
Oxygenation status 
• 
Bleeding Measures 
• 
Evaluation of primary endpoint components including all-cause mortality, ICH, major bleeding, clinical 
deterioration and/or escalation to a bailout therapy, and ICU admission and ICU length-of-stay 
• 
Adverse event assessment 
 
Note that the Discharge Visit can be done at the same time as the 24-hour visit or the 30-day visit, if applicable.  
However, if two visits are completed on the same day, both CRFs will need to be filled out.  There are no windows 
from Index Procedure determining when the Discharge Visit must be completed.  Rather, the Discharge Visit is 

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completed when the patient is discharged from the hospital and the assessments are completed within the 12 
hours prior to discharge.  If the subject has not been discharged from the hospital by the 30-day visit, then the 
Discharge Visit is missed and the 30-day assessment (including evaluation of primary endpoint components) and 
patient exit is completed. 
Note that the evaluation of endpoint considerations include All-cause mortality, ICH, Major bleeding, Clinical 
deterioration and/or escalation to a bailout therapy, and ICU admission and ICU length-of-stay.  These are assessed 
at hospital discharge or 7 days after the index procedure, whichever is earlier.  If a subject is still in the hospital and 
exits the study for any reason before the 30-day Visit, evaluation of primary endpoint components should be 
completed at the time of patient exit. 
30-day visit:  The following assessments will be performed at the 30 day visit (30 days +15 days): 
• 
Anticoagulation regimen 
• 
mMRC dyspnea score, Borg, and NYHA 
• 
Oxygenation status 
• 
PEmb-QoL and EQ-5D-5L  
• 
Adverse event assessment 
The 30-day visit assessments can be conducted in-person or remotely, if allowed by the IRB/EC. 
The patient will be exited from the study at this visit if not already exited earlier for other reasons. 
Note that the evaluation of endpoint considerations include All-cause mortality, ICH, Major bleeding, Clinical 
deterioration and/or escalation to a bailout therapy, and ICU admission and ICU length-of-stay.  These are assessed 
at hospital discharge or 7 days after the index procedure, whichever is earlier.  If a subject is still in the hospital and 
exits the study for any reason before the 30-day Visit, evaluation of primary endpoint components should be 
completed at the time of patient exit. 
UNSCHEDULED FOLLOW UP VISITS  
The study will only record subject visits during the follow up period (defined as discharge through completion of 
the 30-day visit, up to a maximum 45 days from Index Procedure) that are related to the patient’s PE condition and 
treatment. The following assessments will be performed at the unscheduled visit: 
• 
Anticoagulation regimen 
• 
Adverse event assessment 
WITHDRAWALS AND LOST TO FOLLOW UP  
Participation is completely voluntary, and each subject is free to withdraw consent to participate in the study at 
any time. An investigator also has the right to withdraw the subject from the study for reasons concerning the 
health or well-being of the subject, or in the case of lack of cooperation. Should a subject decide to withdraw 
consent for any reason, or should the investigator decide to withdraw the subject, all efforts will be made to 
complete and report the observations up to the time of withdrawal as thoroughly as possible. A complete final 
evaluation at the time of the subject’s withdrawal must be made and an explanation given as to why the subject is 
withdrawing or being withdrawn from the study. 
The reason for, and date of, withdrawal must be recorded on the subject’s Study Exit CRF. If the reason for the 
withdrawal is a device, drug, or procedure-related AE, the event must be reported to the Sponsor and recorded in 
the CRF. 

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If the index catheter-based intervention procedure is aborted before treatment catheter insertion or is not 
performed, the subject is considered a screen fail.  
All efforts will be made to return subjects for all follow up visits.  Due diligence in reaching the subject must be 
made by two documented telephone contact attempts, emails, or regular postal mail letters.  After the above 
attempts are made, if no response from the subject or their designated caregiver is obtained, the final evaluation 
of the subject and study exit will be dated on the last visit at which study-related assessments were performed.  
The Study Exit CRF page will be completed, and communication attempts will be documented. 
COVID-19 EFFECT ON RESEARCH 
This study was designed to compare the clinical outcomes of patients treated with the FlowTriever System versus 
Catheter-Directed Thrombolysis (CDT) for use in acute pulmonary embolism (PE).  As a result of the COVID-19 
pandemic, clinical practice patterns may be affected, and subject visits may be postponed or eliminated.  
Additionally, subjects may not be willing to be seen by their provider potentially exposing both parties to the virus.  
In order to protect subject and provider safety, some data may be collected from subjects over the phone if 
allowed by the IRB/EC.   
8. RISK ANALYSIS 
RISKS TO SUBJECTS 
The PEERLESS Study involves the use and disclosure of deidentified health information. It collects only information 
relevant to the subject’s PE condition and treatment.   
The PEERLESS Study involves the collection of specific information for research and educational purposes only. It 
does not specify how the FlowTriever System or CDT will be used to treat PE (all products are commercially 
available), and other than allocation to a therapy strategy for subjects in the RCT Cohort, decisions regarding a 
subject’s treatment are not influenced by the PEERLESS Study.   Physicians participating in the PEERLESS Study are 
expected to review the indications, contraindications, warnings, precautions, and safety events described in the 
IFUs and/or Investigator Brochure, as applicable. As with any endovascular procedure, thrombolytic or 
anticoagulation administration, the treating physician is expected to counsel the subject on the risks and benefits 
specific to the planned treatment and to obtain the local, procedure-related, or treatment-related informed 
consent per institutional policies and procedures. 
RISK MITIGATION 
The PEERLESS Study was designed to evaluate subject outcomes for PE Treatment using the FlowTriever System 
and catheter-directed thrombolytics (CDT). The risks of providing this personal health information have been 
mitigated, as no personal information directly identifying the subject will be collected in the study database.   At 
the time of participation, each participant will be assigned a unique study identification number. This number will 
be used in the database to identify the subject. All data handling will be in accordance with GDPR and HIPAA 
requirements and only de-identified information will be entered into the study database. 
STUDY JUSTIFICATION 
The Inari FlowTriever System offers an efficient treatment option for PE subjects without the need for thrombolytic 
drugs and the accompanying high bleeding risk including intracranial hemorrhage.  The use of FlowTriever may 
provide quicker relief due to the mechanical approach to clot removal compared to a pharmacological approach, 
which can take several hours to show an effect.  The study is designed to assess the treatment outcomes in acute 
subjects receiving FlowTriever Mechanical Thrombectomy versus subjects receiving Catheter-Directed 
Thrombolysis (CDT).  Due to lack of evidence in the treatment of PE, this study will compare outcomes amongst 

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two of the most common advanced therapies.  This study may guide therapies to minimize ICU bed usage 
providing potential benefit to cost and patient care. 
9. SAFETY ASSESSMENT  
DEFINING ADVERSE EVENTS 
An Adverse Event (AE) is an untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons, whether or not related to the 
investigational* medical device and whether anticipated or unanticipated (ISO 14155:2020, 3.2). 
*NOTE 1:  All medical devices in the context of this clinical trial are considered investigational devices. 
 NOTE 2: This adverse event definition includes events related to the procedures involved. 
Disease signs and symptoms that existed prior to study participation are not considered AEs unless the disease or 
condition recurs after the subject has recovered from pre-existing condition, or the disease or condition worsens in 
intensity or frequency during the study. 
Collection of adverse events will start after point of enrollment. Adverse events will be monitored throughout the 
study. Investigators must obtain all information available to determine the causality and outcome of the AE and to 
assess whether it meets the criteria for classification as a serious adverse event (SAE) requiring immediate 
notification to the sponsor or its designated representative. All reported AEs will be documented on the 
appropriate CRF and will include the event description (sign, symptom, or diagnosis), timing of onset and 
resolution, seriousness, severity, cause, and action taken. The investigator must assess causality and severity for all 
AEs. 
All AEs will be followed by the Investigator until resolution or until the 30 Day follow up visit is completed or until 
study exit.  When the study subject’s participation in PEERLESS has ended, after the 30-Day follow-up visit or in 
case of patient withdrawal, the patient will continue to be treated and followed-up as per the hospital’s standard 
of care. 
DEFINING ADVERSE DEVICE EFFECT (ADE)  
An Adverse Device Effect (ADE) is an AE related to the use of an investigational medical device.  
NOTE 1: This definition includes AEs resulting from insufficient or inadequate instructions for use, deployment, 
implantation, installation, or operation, or any malfunction of the investigational medical device.  
NOTE 2: This definition includes any event resulting from an error use or from intentional misuse of the 
investigational medical device.   
NOTE 3: This includes ‘comparator’ if the comparator is a medical device. (ISO 14155:2020, 3.1) 
DEFINING SERIOUS ADVERSE EVENT (SAE) 
A Serious Adverse Event (SAE) is an adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users or other persons as defined by one or more of 
the following:  

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1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, including chronic disease, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function, 
5) fetal distress, fetal death or a congenital abnormality or birth defect including physical or mental 
impairment 
NOTE 1: Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, without serious 
deterioration in health, is not considered an SAE.  (ISO 14155:2020, 3.45) 
DEFINING SERIOUS ADVERSE DEVICE EFFECT (SADE) 
A Serious Adverse Device Effect (SADE) is an adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event.  (ISO 14155:2020, 3.44) 
DEFINING UNANTICIPATED/ANTICIPATED SERIOUS ADVERSE DEVICE EFFECT (USADE/ASADE) 
A USADE is a serious adverse device effect which by its nature, incidence, severity or outcome has not been 
identified in the current risk assessment.  
An ASADE is an anticipated serious adverse device effect which by its nature, incidence, severity or outcome has 
been identified in the risk assessment.   (ISO 14155:2020, 3.51) 
DEFINING UNANTICIPATED ADVERSE DEVICE EFFECT (UADE) 
An unanticipated adverse device effect (UADE) is any serious adverse effect on health or safety or any life-
threatening problem or death caused by, or associated with, a device, if that effect, problem, or death, was not 
previously identified in a nature, severity, or degree of incidence in the investigational plan or application 
(including a supplementary plan or application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects. (21 CFR 812.3(s)) 
DEVICE DEFICIENCY (DD) 
A Device Deficiency (DD) is the inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, usability, safety or performance.  
 NOTE 1: DD include malfunctions, use errors and inadequacy in the information supplied by the manufacturer 
including labeling.  
NOTE 2: This definition includes device deficiencies related to the investigational medical device or the 
comparator. (ISO 14155:2020, 3.19)   
EVENT SEVERITY 
The severity of an adverse event is a qualitative judgment of the degree of intensity, as determined by the 
investigator or as reported by the subject. The severity of the adverse event should be evaluated according to the 
following scale: 

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• 
Mild: No limitation of usual activities, no therapy or only symptomatic therapy required to treat the injury 
or illness. 
• 
Moderate: Some limitation of usual activities or specific therapy is required. 
• 
Severe: Inability to carry out usual activities, hospitalization, emergency treatment, life threatening 
events, or death. 
The assessment of severity should be made independent of the relationship to the device and therapy or the 
seriousness of the event. 
EVENT RELATIONSHIP 
The investigator will categorize the relationship of the adverse event as follows: 
• 
Device-related: The event is directly related to the FlowTriever System or CDT system, as defined by its 
intended use. AEs will be considered unrelated to the device if the complication could have occurred if the 
device functioned entirely within its specifications. 
• 
Procedure-related: Procedure-related events include all AEs that occur at any time of patient 
participation that was directly related to the procedure. The exception to this rule is an event that is 
device-related; such events should not also be classified as procedure-related. 
• 
Drug-related: Event is attributable to thrombolytic or anticoagulant therapy. These events may occur 
from inadequate (thrombosis) or excessive therapy (bleeding). A drug-related AE cannot also be classified 
as device-related, but many will be classified as procedure-related, since the drug may be part and parcel 
of the index procedure. 
ADVERSE EVENT REPORTING 
Subjects will be carefully monitored during the study for possible adverse events. Any adverse event that occurs 
after the time of enrollment through end of study participation will be fully evaluated by the investigator. 
Appropriate treatment will be initiated for AEs and the study follow up will continue as completely as possible. 
The investigator will document all observations and clinical findings of adverse events, including the nature, 
severity and relationship, on the appropriate CRFs.  
For US sites, the investigator is required to report all SAEs as soon as possible but no later than 5 calendar days 
upon learning of the SAE. All UADEs must be reported to the sponsor within 24 hours after first learning of the 
event.  
For European sites, the investigator is required to report all SAEs as soon as possible but no later than 3 calendar 
days upon learning of the SAE. All UADEs and device deficiencies must be reported to the sponsor within 24 hours 
after first learning of the event.  
The investigator must follow their local IRB/EC policy for SAE/UADE reporting.  UADEs have special reporting 
requirements. The sponsor will notify the sites, IRBs/ECs and regulatory bodies as per specific regulations. 
The investigator will send the completed AE CRF and all available supporting source documentation to the sponsor. 
As additional information becomes available, the investigator will record all adverse events (serious and non- 
serious), unanticipated adverse device effects, device deficiencies, product complaints, or other reportable safety 
events on the appropriate CRFs. Copies of source documentation which contain significant information related to 
the event such as progress notes, consultations, nurse’s notes, operative reports and subject summaries etc. are 
required for evaluation of the event. Copies of such documentation shall be obtained from the investigator (de-
identified as to the subjects’ identity) and provided to the sponsor. 

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Regarding subject deaths, it is requested that a copy of the death certificate and a copy of the autopsy report, if 
applicable, be sent to the sponsor when available. Any other source documents related to the death should also be 
provided to the sponsor. In the event that no source documents are available, the PI is required to describe the 
circumstances of the subject’s death in a letter, e-mail, or other written communication. 
Clinical Events Committee (CEC) 
A Clinical Events Committee (CEC) will be utilized in this study for the purposes of adjudicating safety related 
primary and secondary endpoints.  Site-reported safety and outcome data will be provided to the CEC for review 
and adjudication of the following items for all subjects enrolled in the study. 
Events to be adjudicated by the CEC are as follows: 
Safety related Primary Endpoint: 
• 
All-cause mortality 
• 
Intracranial hemorrhage (ICH) 
• 
Major bleeding per ISTH definition4  
• 
Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout 
therapy 
Safety related Secondary Endpoints: 
• 
All-cause mortality within 30 days from index procedure 
• 
PE-related and all-cause readmission within 30 days from index procedure 
• 
Device and drug-related serious adverse events within 30 days from index procedure 
• 
Clinically Relevant Non-Major (CRNM) and Minor bleeding events before hospital discharge up to a 
maximum of 7 days after the index procedure 
For each event presented to the CEC, the following parameters will be adjudicated: 
• 
Determination if event meets an endpoint definition 
• 
Determination if the event is a Serious Adverse Event (SAE) 
• 
Determination of relatedness (unrelated, related, unknown): 
o 
Relation to the Index Procedure 
o 
Relation to the Index Device 
o 
Relation to subsequent thrombus removal Device/Therapy (Bailouts) 
o 
Relation to thrombolytic therapy 
o 
Relation to anticoagulation therapy 
• 
Determination of severity (mild, moderate, or severe) 
Event adjudication will be conducted according to the CEC Charter. 
PRODUCT COMPLAINT REPORTING 
Product complaint and vigilance reporting are applicable and AEs related to any market-released device during the 
study must be reported. The reporting of product complaints is not part of the study and should be done in 
addition to the AE reporting requirements per local regulations for market released product.  

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Product Complaint: Any written, electronic or oral communication that alleges deficiencies related to the identity, 
quality, durability, reliability, safety, effectiveness or performance of a medical device that has been placed on the 
market. 
In addition, the sponsor will comply with Medical Device Reporting (MDR) requirements. (21CFR803, EU MDR 
2017/745. 
10. STATISTICS & DATA ANALYSIS  
SAMPLE SIZE 
By assuming an 80% power with one-sided alpha of 2.5%, the win ratio methodology is applied to the primary 
endpoint that consists of five components. The required sample size is 432 subjects (216 subjects per arm); and 
planning for follow up attrition and further describing secondary endpoints/exploratory analysis, the study will 
enroll up to a total of 550 randomized subjects (RCT Cohort). The sample size assumptions are based on Inari 
sponsored studies and a review of literature.  
Up to 150 additional subjects who meet all eligibility criteria and who have an absolute contraindication to 
thrombolytics, whose initial planned primary treatment strategy includes FlowTriever, will be enrolled as part of 
the Contraindication Cohort.  The same clinical assessments and follow up schedule will be administered in this 
cohort as is described for the RCT Cohort.  The Contraindication cohort data will not be used for any PEERLESS 
protocol-defined hypothesis testing nor used to calculate any primary or secondary endpoints. 
STATISTICAL METHODOLOGY 
The statistical design objective for this trial is to compare the clinical outcomes of the FlowTriever System versus 
Catheter-Directed Thrombolysis (CDT) for use in the treatment of acute pulmonary embolism (PE). Since the 
primary endpoint is a composite clinical endpoint, a modified generalized Wilcoxon test (F-S test) proposed by 
Finkelstein & Schoenfeld73 will be applied to examine the performance differences between the two treatment 
arms.  
In this trial, the primary endpoint is a hierarchy of five clinical outcome components. Each subject in the study will 
be compared to each of the other subjects in a pairwise manner, regardless of which treatment arm the compared 
subject is in, and assigned a score, 𝑢𝑢𝑖𝑖𝑖𝑖, of 1, -1, or 0, depending on whether the comparison has a favorable, 
unfavorable, or unsettled outcome in the hierarchy of the clinical events; i is the index subject to be compared 
with all other subjects in a pairwise fashion and j represents jth subject comparison. For example, if a subject i is 
alive while a subject j died, the score is 1; if a subject i died while subject j is alive, the score is -1. If both subjects 
are alive or dead, the second clinical outcome (Intracranial hemorrhage) is compared and assigned a score of 1, -1, 
or 0 in a similar comparison logic. Subsequently, within each pairwise comparison, the score is determined by 
comparing five clinical outcomes sequentially in the order of outcome priorities. In summary, for each pair of 
subjects (i, j), the score is defined as 
𝑢𝑢𝑖𝑖𝑖𝑖= ൝
   1, if subject 𝑖𝑖 does better than subject 𝑗𝑗
−1, if subject 𝑗𝑗 does better than subject 𝑖𝑖
  0, if it cannot be determined                   
 
Finkelstein & Schoenfeld73 then assigned a score 𝑈𝑈𝑖𝑖= ∑
𝑢𝑢𝑖𝑖𝑖𝑖
𝑖𝑖≠𝑗𝑗
 to each subject i. Their proposed test is a score test 
based on the sum of the ranks for the treated group (see the following eqation). 
𝑇𝑇= ෍𝑈𝑈𝑖𝑖𝐷𝐷𝑖𝑖
𝑁𝑁
𝑖𝑖=1
 

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where  𝐷𝐷𝑖𝑖= 1 for subjects in FlowTriever arm and 𝐷𝐷𝑖𝑖= 0 for subjects in CDT arm, and N is the number of total 
subjects in the trial. The proposed FS statistic for the hypothesis of interest is 𝑇𝑇
√𝑉𝑉
ൗ
, where 𝑉𝑉=
𝑛𝑛𝐹𝐹𝐹𝐹𝑛𝑛𝐶𝐶𝐶𝐶𝐶𝐶
𝑁𝑁(𝑁𝑁−1) ∑𝑈𝑈𝑖𝑖
2
𝑖𝑖
 is 
the variance of T, 𝑛𝑛𝐹𝐹𝐹𝐹 and 𝑛𝑛𝐶𝐶𝐶𝐶𝐶𝐶 are the number of subjects in FlowTriever and CDT arms, respectively, and 𝑛𝑛𝐹𝐹𝐹𝐹+
 𝑛𝑛𝐶𝐶𝐶𝐶𝐶𝐶= 𝑁𝑁. The hypothesis is tested by comparing the FS statistic to the standard normal distribution (Finkelstein 
& Schoenfeld, 1999)73.  
To determine the sample size required to achieve 80% power given one-sided alpha of 2.5%, we first will simulate 
subject level data per data replicate. For a data replicate and within a treatment arm, clinical outcomes with event 
proportions are sampled from binomial distribution; ICU is from a multinominal distribution with 3 categories, 
including no ICU admission, < 24 hours, and ≥24 hours. We will assume each clinical outcome is independent of 
each other. For example, we may sample 100 subjects per treatment arm, and within each treatment arm has 
different clinical outcome proportions or means. Once we generate 200 subjects in total (100 per treatment arm), 
we may derive the F-S test statistic and its p-value. We will then repeat the process for 2,500 data replicates and 
derive 2,500 p-values based on F-S test statistics; power is the proportion of p-values that are ≤ 0.05. Each given 
sample size number will thus lead to one power number to be calculated. As we alter the sample sizes in the 
simulation scenario, we can conduct a grid search to determine the minimal sample size required to achieve at 
least 80% power. 
In addition, the win ratio defined by Pocock el al.,74 will be reported to summarize the performance differences 
between two treatment arms. The win ratio is defined as 
𝑁𝑁𝑊𝑊
𝑁𝑁𝐿𝐿, where 𝑁𝑁𝑊𝑊 is the number of winners for the 
FlowTriever System (i.e., counting the number of pairs in which the subject in FlowTriever System does better than 
that in CDT arms), and 𝑁𝑁𝐿𝐿 is the number of losers for the FlowTriever System (i.e., counting the number of pairs in 
which the subject in FlowTriever System does worse than that in CDT arms); the 95% CI of the win ratio estimate 
can be derived via a bootstrap method.  
The analysis population for primary and secondary endpoints is described in the statistical analysis plan (SAP). 
Meanwhile, for the contraindication cohort, the descriptive summary will be provided. 
11. STUDY MANAGEMENT CONSIDERATIONS  
PROTOCOL MODIFICATIONS 
No changes from the final approved study protocol will be initiated without the IRB/EC prior written approval of 
the amendment. The Principal Investigator will acknowledge the amendment by signing the Protocol Signature 
Page. 
PROTOCOL DEVIATIONS 
A protocol deviation is the non-adherence to or divergence from the protocol-required study procedures. For 
example, the inclusion and exclusion criteria, improper or lack of consent, and lack of IRB/EC approval would all be 
considered protocol deviations. Non-compliance with required assessments or out of window visits will result in a 
protocol deviation. 
The Sponsor will address deviations and take appropriate corresponding action. Protocol deviations will be 
reported to the IRBs/ECs by the sponsor and/or clinical sites, per local requirements.  Continued non-compliance 
with the study protocol may lead to termination of the Investigator’s participation in the study. 
INFORMATION FOR STUDY PERSONNEL 
The Sponsor or designee is responsible for explaining the protocol to all study staff, including the Investigator, and 
for ensuring their compliance with the protocol throughout the study. Additional information will be made 

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available during the study when new staff become involved in the study, and as otherwise agreed upon with either 
the Investigator or the Sponsor or designee. 
The Investigator is responsible for giving information about the study to all staff members involved in the study or 
any element of patient management, both before starting the study and during the study (e.g., when new staff 
become involved). The Investigator must ensure that all study staff members are qualified by education, 
experience, and training to perform their specific responsibilities. 
12. STUDY ADMINISTRATION  
SITE SELECTION AND QUALIFICATION 
A Site Qualification Visit (SQV) may be conducted by the Sponsor or designee in-person or via teleconference.  
Study sites and Investigators will be selected based on a variety of factors including, but not limited to, experience 
with endovascular techniques, access to required facilities and equipment, sufficient and adequately trained 
personnel, and availability of potential subjects. The criteria used for determination will be documented. 
SITE INITIATION 
A Site Initiation Visit (SIV) may be conducted by the Sponsor or designee in-person or via teleconference to ensure 
proper training of the Investigator and study staff members regarding the study protocol and data collection, as 
well as to ensure regulatory requirements are fulfilled prior to enrollment of the first study subject at a site. 
SITE MONITORING 
Interim monitoring visits may be conducted by the Sponsor or designee in-person or remotely to ensure 
compliance with the protocol, and other written instructions and regulatory guidelines according to a study-
specific monitoring plan. 
The main responsibilities of the Monitor or designee are to ensure adherence to the protocol; to verify all data are 
correctly and completely recorded and reported; confirm that informed consent is obtained and recorded for each 
subject before any medical record or personal health information is shared with any study representatives. The 
Investigator and assisting staff must agree to cooperate with the Monitor or Sponsor representative to resolve any 
study-related action items, errors, or possible misunderstandings concerning the findings detected during these 
monitoring visits or data review. 
SITE CLOSE-OUT 
A Site Close-out Visit (COV) visit may be conducted by the Sponsor or designee in-person or via teleconference to 
ensure proper close-out and archiving of trial documentation.  This may be combined with a final Interim 
Monitoring Visit.  Any COVs performed will be documented and kept in the study files. 
STUDY TERMINATION 
Inari Medical and applicable regulatory authorities have the right to terminate the entire study or a specific study 
site at any time. Situations that could warrant study termination include, but are not limited to: 
• 
Increased incidence of adverse experiences and/or the severity of such, suggestive of a potential, device-
related health hazard 
• 
Insufficient subject enrollment rates 
• 
Recurrent protocol deviations or other non-compliances 
• 
Inaccurate, incomplete, and/or untimely data recording on a recurrent basis 

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• 
Lack of cooperation with monitoring visits (e.g., failure to adequately prepare for visits, address action 
items from one visit to the next, or provide access to medical records) 
DATA HANDLING AND RECORDKEEPING 
Completing, Signing and Archiving Case Report Forms 
Clinical study data will be collected using electronic case report forms (eCRFs). A web-based electronic data 
capture (EDC) database will be used to record and manage study data. eCRF completion guidelines and instructions 
for electronic data-entry will be developed in conjunction with the Sponsor and/or EDC vendor. All eCRFs must be 
kept in good order and updated so they always reflect the latest observations on the subjects participating in the 
study. 
The Investigator will sign the appropriate eCRF pages and source documentation. Pertinent eCRF corrections will 
be made electronically and signed electronically by the Investigator. An embedded audit trail will capture the date, 
time, and user making entries and changes to the electronic data. 
It is important to have proper data collection in a timely manner (approximately 5 business days of the study 
visit/assessment).  When the Sponsor or designee requests additional data or clarification of data for the eCRF, the 
request must be answered satisfactorily in a timely manner. 
Data Management and Archiving 
The Sponsor and/or designee will be responsible for the processing and quality control of the data. All CRFs, copies 
of protocols and protocol amendments, correspondence, subject identification lists, informed consent forms, and 
other essential documents must be retained for a minimum of 10 years post study completion or 10 years after the 
last FlowTriever system or CDT system has been placed on the market (whichever is longer).  
No study document or image will be destroyed without prior written agreement between the Sponsor and the 
Investigator prior to the conclusion of the retention period. Should the Investigator wish to assign the study 
records to another party or move them to another location, advance written notice must be given to the Sponsor. 
Direct Access to Source Data/Documentation 
The Investigator must maintain the primary records (i.e., the original source of the data/source documents) of 
each subject’s data. Examples of source documents are hospital records, office visit records, examining physician’s 
findings or progress notes, consultant’s written opinion or notes, laboratory reports, imaging data, and worksheets 
that are used as the source. 
The Investigator may keep a separate subject identification list showing enrollment numbers and names to allow 
unambiguous identification of each subject included in the study.  The Sponsor will not collect subject 
identification lists. 
The Sponsor, auditors, and health authority inspectors (or their agents) will be given direct access to source data 
and documentation (e.g., medical chart/records, laboratory test results, images) for source data verification, 
provided that patient confidentiality is maintained in accordance with local requirements. 

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13. ETHICS AND CONFIDENTIALITY  
INFORMED CONSENT 
It is the Investigator’s responsibility to ensure written or electronic (if applicable) Informed Consent is obtained for 
each study subject in accordance with applicable regulations (e.g., ISO 14155-1, 21 CFR Part 50). 
Subjects will be screened to determine their initial eligibility and interest in the study.  Written or electronic (if 
applicable), study-specific Informed Consent will be obtained from each subject via the current IRB/EC approved 
Informed Consent Form (ICF) prior to the subject’s participation in any study-related procedures, and prior to de-
identified medical record or personal health information (PHI) being shared with any study representative. The 
subject’s willingness to participate in the study will be documented in a study-specific Informed Consent Form, 
which will be signed and dated by the subject or their Legally Authorized Representative.  The subjects will also be 
informed about study purpose, alternative treatments, potential risks/benefits of study participation, and the 
study assessment schedule. 
The Investigator will keep the original consent form and a copy may be given to the subject. It will be explained to 
the subjects that they are free to refuse entry into the study and free to withdraw from the study at any time 
without prejudice to future treatment.  
If, at any time during the study, new information becomes available or a protocol amendment requires an 
amendment to the ICF, active subjects may be asked to re-consent by signing an updated ICF.  Copies of all signed 
ICFs will be maintained by the Investigator and will be made available to the Sponsor for monitoring purposes.  
INSTITUTIONAL REVIEW BOARD (IRB) / ETHICS COMMITTEE (EC) 
This study must be approved by an appropriate IRB/EC at each study site. Securing IRB/EC approval is the 
responsibility of the Investigator, as defined by GCP, ISO 14155-1 and FDA regulations (21 CFR Part 56), prior to 
starting the study.  
The Sponsor must receive a copy of the IRB/EC approval letter (or equivalent documentation) for the study 
protocol and Informed Consent Form before the study can be started at that site. 
The IRB/EC and Sponsor must approve any changes to the protocol, as well as a change of Principal Investigator. 
Documentation of IRB/EC approval must be provided to the Sponsor. Records of all study review and approval 
documents must be maintained by the Investigator in the Study File/ Regulatory Binder and are subject to 
inspection by the Sponsor (or designee) or regulatory authority during or after completion of the study.  
The Investigator must notify the IRB/EC, as per their reporting guidelines, and the Sponsor when he or she deviates 
from the protocol. The Sponsor must be notified of all relevant action taken by the IRB/EC and must receive a copy 
of all study-related correspondence between the Investigator and the IRB/EC. 
The IRB/EC must receive notification of study completion and a final report upon study completion or closure. A 
copy of these reports must be provided to the Sponsor. The Investigator must maintain an accurate and complete 
record of all submissions made to the IRB/EC. 
STUDY SUBJECT CONFIDENTIALITY 
The Investigator must ensure that the privacy of all subjects, including their personal identity and all personal 
health information. In CRFs and other documents or image material submitted to the Sponsor, subjects will not be 
identified by their names, but by an individual identification code (i.e., subject identification number). 

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Personal medical information may be reviewed for the purpose of verifying data recorded in the CRFs. A monitor 
or Sponsor designee may conduct source-document verification on behalf of the Sponsor, the quality assurance 
unit, or regulatory authorities. Personal medical information will always be treated, also when sent abroad, as 
confidential and handled in compliance with the Health Insurance Portability and Accountability Act (HIPAA) and 
General Data Protection Regulation (GDPR). 
 INDEPENDENT IMAGE REVIEW AND IMAGE TRANSFER 
An independent reviewer may be utilized in the study, at the Sponsor’s discretion. The independent reviewer will 
evaluate selected CT and Echocardiography images collected at baseline, 24 hours, and any unscheduled visits (if 
collected).  
De-identified, electronic echocardiograms and CT images will be sent via secure electronic transfer to a secured 
imaging repository per US FDA/EU GDPR regulations. Where an electronic submission is not possible, de-identified 
images will be sent by other secure means per US FDA/EU GDPR regulations.  Copies of images will be securely 
stored for a minimum of 10 years post study completion or 10 years after the last FlowTriever system or CDT 
system has been placed on the market (whichever is longer).   
 
INVESTIGATOR RESPONSIBILITIES 
Investigator responsibilities include, but are not limited to, the following: 
• 
Conducting the study in accordance with this investigational plan, signed agreement, GCP, and applicable 
regulations protecting the rights and safety of study subjects 
• 
Ensuring that informed consent is obtained for each study subject in accordance with GCP and applicable 
regulations (e.g., ISO 14155-1, 21 CFR Part 50) 
• 
Ensuring that IRB/EC approval is secured prior to starting the study and ensuring continuing review and 
approval as required throughout the investigation 
• 
Ensuring all associates, colleagues, and employees assisting in the conduct of the study are informed 
about their obligations, are adequately qualified and trained, and meet their commitments 
• 
Maintaining adequate and accurate records and ensuring those records are available for inspection at any 
time 
• 
Ensuring that conducting the study does not give rise to a conflict of interest (financial disclosure is 
required)  
14. ELECTRONIC DATA 
Electronic data will only be accessible to authorized personnel with a unique user identifier and password for the 
EDC. Passwords will be set to expire periodically. Access to electronic study data will be provided to research 
personnel upon completion of training. Read and write access will be provided to investigational sites but only for 
information and subject data at their site. The Sponsor and designee will have read-only access and can post 
queries for potential data-related discrepancies. 
15. PUBLICATION OF TRIAL RESULTS 
A description of the clinical trial results will be available on http://www.ClinicalTrials.gov (Ref: NTC05111613), 
within 1 year after the completion of the clinical trial. This web site will not include any identifiable subject 
information but will include a summary of the results.  
The sponsor will also seek publication of the trial primary and secondary objectives in international peer-reviewed 
journals. 

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16. FUTURE USE OF DATA FOR RESEARCH PURPOSES 
The subject clinical data and echocardiography images collected in the PEERLESS Study could play an important 
role in answering clinical questions in the future and could therefore be used in clinical investigations that have not 
been defined yet (= further use).  
For research projects with not yet defined research questions we will collect the consent for “further use of data” 
and only data from patients who agreed to the “further use of data” will be considered. 
17. TERMS AND DEFINITIONS  
Primary Endpoint Definitions 
Index Procedure 
The index procedure begins when access for treatment is obtained.  The 
index procedure is considered complete when the subject leaves the 
procedure room. 
Intracranial Hemorrhage 
Intracranial hemorrhage (ICH) is defined as ANY bleeding involving the brain 
parenchyma, ventricular system, or subarachnoid, subdural, or epidural 
regions, as identified by CT scan or MRI, regardless of symptoms. 
Major Bleeding 
 
ISTH Major Bleeding4 in non-surgical subjects: 
• 
Fatal bleeding;  
and/or  
• 
Symptomatic bleeding in a critical area or organ, such as 
intracranial, intraspinal, intraocular, retroperitoneal, intraarticular 
or pericardial, or intramuscular with compartment syndrome;  
and/or  
• 
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. 
Clinical Deterioration 
 
Clinical deterioration is defined as documented objective hemodynamic or 
respiratory worsening that is new (i.e. not present at the time of 
enrollment).   
Clinical deterioration is when one or more of the following is definitively 
documented, with relation to both the severity and the duration of the 
event: 
• 
Hypotension with systolic blood pressure <90 mm Hg lasting at 
least 30 minutes, unresponsive to fluid resuscitation, and 
requiring the addition of or increased dose of vasopressors 
• 
Fall in systolic blood pressure by 40 mm Hg or more, lasting at 
least 30 minutes, and accompanied end-organ hypoperfusion 
(such as oliguria, mental status changes, ischemic extremities) 
• 
Cardiac arrest requiring cardiopulmonary resuscitation 
• 
Bradycardia lasting more than 10 minutes, accompanied by 
hypotension, and requiring pharmacologic intervention or 
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• 
Ventricular tachycardia or fibrillation requiring pharmacologic 
intervention or defibrillation 
• 
Requirement for an increase in fraction of inspired oxygen 
requirements 0.20 or greater, lasting longer than 30 minutes (e.g. 
from 0.21 to 0.41) 
• 
Need for intubation in a previously non-intubated subject, or 
unplanned use of extracorporeal membrane oxygenation (ECMO) 
Note that transient fluctuations in hemodynamic and/or respiratory 
function may be common during thrombectomy and thrombolysis 
procedures, and events not meeting both severity and duration 
requirements are not considered meeting the definition of Clinical 
Deterioration.  Such changes may resolve spontaneously upon 
continuation of an existing treatment plan, and as such are unremarkable.  
Vagal episodes are also, in themselves, not considered Clinical 
Deterioration.  Shorter term changes in hemodynamic or respiratory 
function, when accompanied by an unplanned escalation of therapeutic 
measures under the primary clinician’s judgement to avoid overt 
deterioration, may be considered Bailout Therapy.  Any such escalations of 
therapy will be documented in detail and adjudicated by a Clinical Events 
Committee (CEC). 
Bailout 
Bailout therapy is an unplanned escalation of therapeutic measures, taken 
when the patient’s condition has not improved or is not improving 
according to expectations.  Potential Bailout Therapy events will be 
adjudicated by a Clinical Events Committee, including when any of the 
following occur: 
• 
Unplanned use of additional mechanical, pharmacomechanical, 
pharmacologic catheter-based therapies, or systemic 
thrombolytics, or changing from the assigned treatment strategy, 
after initial treatment strategy as assigned was initiated. 
o 
If catheter-directed thrombolysis (CDT) was the assigned 
treatment strategy and emergent/clinically driven 
systemic thrombolytic administration (e.g. ≥ 10 mg tPA) 
was required after CDT was initiated, this would be 
considered a bailout.  
 
If the length of thrombolytic administration is 
simply extended and is not emergent or 
clinically driven, this would not qualify as a 
bailout.   
o 
If mechanical thrombectomy was the assigned 
treatment strategy, low-dose catheter-directed 
adjunctive thrombolytic therapy (less than 10 mg tPA) 
that is administered intra-procedurally or post-
procedurally will be strongly discouraged but not 
considered a bailout 
• 
Surgical thrombectomy 
Before escalating to a Bailout Therapy, physicians are encouraged to 
consider the patient’s condition and identify one or more reasons from the 

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following list to justify the need for Bailout Therapy.  These reason(s) will 
be documented in the study case report forms (CRFs).  
• 
Persistent elevated respiratory rate 
• 
Ongoing or increased requirement for supplemental oxygen 
• 
Persistent or new-onset tachycardia 
• 
Sustained or sudden bradycardia 
• 
Sudden or persistent hypotension, not associated with a vagal 
episode, or signs of end-organ hypoperfusion 
• 
Hemodynamic worsening or lack of hemodynamic improvement 
• 
Lack of improved lung perfusion, or inadequate clot resolution 
• 
New-onset, persistent, or worsening symptoms of PE 
Any unplanned escalation of therapy adjudicated by the CEC to not meet 
clinical definitions for Bailout Therapies will be considered a protocol 
deviation. 
ICU Admission/ICU Length of Stay 
ICU Admission will be defined as admission or transfer to an Intensive Care 
Unit (ICU), Critical Care Unit (CCU), or similar high-acuity floor, collectively 
referred to as “ICU.”  For the purpose of the endpoint assessment, ICU 
Admission is met under the following conditions: 
• 
Orders are entered for Subject to be admitted or transferred to 
the ICU after the end of the Index Procedure and before hospital 
discharge from the index hospitalization, up to a maximum of 7 
days from the end of the Index Procedure, or 
• 
Subject had been in the ICU leading up to the Index Procedure, 
with plans to return to the ICU immediately after the end of the 
Index Procedure, with or without a transfer to a PACU, recovery 
room, or similar temporary step-down unit according to local 
standard.  
ICU Length of Stay (LOS) is the total number of hours a subject is medically 
required to be in the ICU, measured from the end of the Index Procedure 
or the time of ICU Admission, whichever is later, until the time of an order 
to discharge the subject from the ICU or transfer the subject to a standard 
or lower-acuity unit.  If a subject remains physically located in the ICU due 
to hospital bed availability, transport delays, or other non-medical reasons 
instead of a need for high acuity of care, the time of the order for 
discharge or transfer, rather than the actual time a subject physically 
leaves the ICU, is used for assessing ICU LOS.  
For subjects getting discharged from or transferred off the ICU and 
returning again during the index hospitalization, up to a maximum of 7 
days after the Index Procedure, the total hours of all ICU admissions or 
transfers during that period (i.e., after the Index Procedure and until 
hospital discharge up to a maximum of 7 days) are used for assessing ICU 
LOS. 

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Subjects who had been in the ICU leading up to the Index Procedure, but 
not returning to the ICU after the end of the Index Procedure, are not 
considered to have had an ICU Admission per the endpoint definition. 
For the win ratio primary endpoint, ICU admission and ICU LOS are 
characterized hierarchically as follows: 
1. No ICU Admission 
2. ICU Admission, lasting between 0 – 24 hours 
3. ICU Admission, lasting longer than 24 hours 
 
Additional Safety Definitions 
Adverse Device Effect (ADE) 
An Adverse Device Effect (ADE) is an AE related to the use of an investigational 
medical device.  
NOTE 1: This definition includes AEs resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device.  
NOTE 2: This definition includes any event resulting from an error use or from 
intentional misuse of the investigational medical device.   
NOTE 3: This includes ‘comparator’ if the comparator is a medical device. (ISO 
14155:2020, 3.1) 
Adverse event (AE) 
An Adverse Event (AE) is an untoward medical occurrence, unintended disease 
or injury, or untoward clinical signs (including abnormal laboratory findings) in 
subjects, users or other persons, whether or not related to the investigational* 
medical device and whether anticipated or unanticipated (ISO 14155:2020, 3.2). 
*NOTE 1: All devices used in this study are commercially available and, 
therefore, not considered investigational. 
 NOTE 2: This adverse event definition includes events related to the procedures 
involved. 
CRNM 
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 bleeding4 but does meet at least one of the following 
criteria: 
i. 
requiring medical intervention by a healthcare professional 
ii. 
leading to hospitalization or increased level of care 
iii. 
prompting a face to face (i.e., not just a telephone or electronic 
communication) evaluation 

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Device Deficiency (DD) 
A Device Deficiency (DD) is the inadequacy of a medical device with respect to 
its identity, quality, durability, reliability, usability, safety or performance.  
 NOTE 1: DD include malfunctions, use errors and inadequacy in the information 
supplied by the manufacturer including labeling.  
NOTE 2: This definition includes device deficiencies related to the 
investigational medical device or the comparator. (ISO 14155:2020, 3.19)   
Device-related event 
The event is directly related to the FlowTriever System or CDT system, as defined 
by its intended use. AEs will be considered unrelated to the device if the 
complication could have occurred if the device functioned entirely within its 
specifications. 
Drug-related event 
Event is attributable to thrombolytic or anticoagulant therapy. These events may 
occur from inadequate (thrombosis) or excessive therapy (bleeding). A drug-
related AE cannot also be classified as device related, but many will be classified 
as procedure-related, since the drug may be part and parcel of the index 
procedure. 
Minor bleeding 
Any bleeding not classified as Major Bleeding or Clinically Relevant Non-Major, 
by ISTH definitions 
Procedure-related event 
Procedure-related events include all AEs that occur at any time of subject 
participation that was directly related to the procedure. The exception to this 
rule is an event that is device-related; such events should not also be classified as 
procedure-related. 
Serious Adverse Device Effect 
(SADE) 
A Serious Adverse Device Effect (SADE) is an adverse device effect that has 
resulted in any of the consequences characteristic of a serious adverse event.  
(ISO 14155:2020, 3.44) 
Serious Adverse Event (SAE) 
A Serious Adverse Event (SAE) is an adverse event that led to any of the 
following: 
a) death, 
b) serious deterioration in the health of the subject, users or other 
persons as defined by one or more of the following:  
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body 
function, including chronic disease, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening 
illness or injury or permanent impairment to a body structure 
or a body function, 

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5) fetal distress, fetal death or a congenital abnormality or birth 
defect including physical or mental impairment 
NOTE 1: Planned hospitalization for a pre-existing condition, or a procedure 
required by the CIP, without serious deterioration in health, is not considered 
an SAE.  (ISO 14155:2020, 3.45) 
Unanticipated/Anticipated 
Serious Adverse Device Effect 
(USADE/ASADE) 
A USADE is a serious adverse device effect which by its nature, incidence, 
severity or outcome has not been identified in the current risk assessment.  
An ASADE is an anticipated serious adverse device effect which by its nature, 
incidence, severity or outcome has been identified in the risk assessment.   (ISO 
14155:2020, 3.51) 
Unanticipated Adverse 
Device Effect (UADE) 
An unanticipated adverse device effect (UADE) is any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death, was not previously 
identified in a nature, severity, or degree of incidence in the investigational plan 
or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects. (21 CFR 812.3(s)) 
Other Definitions 
Asymptomatic PE 
Pulmonary embolism detected on an imagining study in a subject without 
clinical symptoms. 
CTED/Post PE Syndrome 
Chronic thromboembolic Disease: Per 2019 ESC Guidelines,1 some subjects may 
present with normal pulmonary hemodynamics at rest despite symptomatic 
disease. If other causes of exercise limitation are excluded, these subjects are 
considered as having chronic thromboembolic disease (CTED).  From 
Respiratory medicine journal on PE, CTED is characterized by similar symptoms 
and imaging findings to CTEPH but without pulmonary hypertension at rest. 
CTEPH 
Chronic thromboembolic pulmonary hypertension:  Per 2019 ESC Guidelines,1 
CTEPH is a disease caused by the persistent obstruction of pulmonary arteries 
by organized thrombi, leading to flow redistribution and secondary remodeling 
of the pulmonary microvascular bed.  The diagnosis of CTEPH is based on 
findings obtained after at least 3 months of effective anticoagulation, to 
distinguish this condition from acute PE. The diagnosis requires a mean PAP of 
≥25 mmHg along with a pulmonary arterial wedge pressure of ≤ 15 mmHg, 
documented at right heart catheterization in a subject with mismatched 
perfusion defects on V/Q lung scan. 
High-Risk PE 
Per ESC guidelines 20191: High-Risk PE determined by hemodynamic instability, 
PESI III-V or sPESI ≥1, RV Dysfunction, and Elevated cardiac troponins.  Note 
definition of hemodynamic instability, which delineates acute high-risk 
pulmonary embolism (one of the following clinical manifestations at 
presentation).  1. Cardiac Arrest: Need for cardiopulmonary resuscitation, 2. 
Obstructive Shock: Systolic BP < 90 mmHg or vasopressors required to achieve a 
BP ≥90 mmHg despite adequate filling status AND end-organ hypoperfusion 
(altered mental status; cold, clammy skin; oliguria/anuria; increased serum 

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lactate), OR 3. Persistent Hypotension: Systolic BP < 90 mmHg or systolic BP 
drop ≥40 mmHg, lasting longer than 15 min and not caused by new-onset 
arrhythmia, hypovolemia, or sepsis 
Intermediate-High-Risk PE 
Per ESC guidelines 20191: Intermediate-High-Risk PE determined by no 
hemodynamic instability, PESI III-V or sPESI ≥1, RV Dysfunction, and Elevated 
cardiac troponins 
Intermediate-Low-Risk PE 
Per ESC guidelines 20191: Intermediate-Low-Risk PE determined by no 
hemodynamic instability, PESI III-V or sPESI ≥1, and 1 or none of the following: 
RV Dysfunction; Elevated cardiac troponins. 
Patient/Subject 
Participants in the study. 
Product Complaint: 
Any written, electronic or oral communication that alleges deficiencies related 
to the identity, quality, durability, reliability, safety, effectiveness or 
performance of a medical device that has been placed on the market. 
Recurrent PE 
Symptomatic worsening from baseline of the embolism that was successfully 
treated with the index procedure with documentation of a change on CTPA or 
other suitable imaging modality. 
Symptomatic PE 
Clinical pulmonary embolism symptoms and/or signs such as chest pain, 
dyspnea, hemoptysis, palpitations, or tachycardia. 
 
 

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Pocock SJ, Ariti CA, Collier TJ, Wang D. The win ratio: a new approach to the analysis of composite 
endpoints in clinical trials based on clinical priorities. Eur Heart J. 2012;33(2):176-82. 
 
 

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FlowTriever Retrieval/Aspiration System and CDT 
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August 23, 2023 
 
 
 
 
 
 
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19. APPENDIX 1 
TABLE A1: KNOWN RISKS FOR FLOWTRIEVER SYSTEM * 
Event Category 
Event 
Cardiac 
Myocardial infarction 
Angina 
Arrhythmias, bradycardia, tachycardia 
Right bundle branch block 
Cardiac tamponade 
Cardiac perforation 
Pericardial effusion 
Valve disruption/injury 
Ventricular rupture 
Hypertension 
Hypotension 
Cardiogenic shock 
Wound 
Access site hematoma 
Peripheral vascular 
Vessel dissection/perforation 
Aneurysm 
Pseudoaneurysm 
Vessel stenosis 
Arteriovenous fistula 
Vascular spasm 
Vasovagal reaction 
Embolism, Distal embolism, foreign body embolism 
Air embolism 
Cerebrovascular 
Stroke/Transient ischemic attack 
Pulmonary 
Perforation of pulmonary arteries 
Pneumothorax 
Pulmonary edema 
Pulmonary infarct 
Hemoptysis 
Respiratory failure 
Miscellaneous 
Fever 
Infection 
Fistulation 

Inari Medical 
FlowTriever Retrieval/Aspiration System and CDT 
Version 4.0 
August 23, 2023 
 
 
 
 
 
 
PEERLESS Study (Protocol 21-002) 
CONFIDENTIAL 
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Event Category 
Event 
Hemoglobinuria 
Hemolysis 
Hypoxemia 
Drug reaction to contrast, thrombolytic or anticoagulation 
Adverse reaction to device materials 
Inflammatory response 
Nausea/vomiting 
General discomfort, tenderness, or pain 
Neurological deficit, peripheral nerve damage 
Organ impairment, renal failure 
Retroperitoneal hemorrhage 
Death 
* From IFUs for FlowTriever Catheter (LB-0047 RevJ), Triever 16 (LB-0060 RevL), Triever 20 (LB-0139 RevM), Triever 
20 Curve (LB-0144 RevJ), and Triever 24 (LB-0151 RevE) 
 
 

Inari Medical 
FlowTriever Retrieval/Aspiration System and CDT 
Version 4.0 
August 23, 2023 
 
 
 
 
 
 
PEERLESS Study (Protocol 21-002) 
CONFIDENTIAL 
Page 68 of 70 
 
TABLE A2: KNOWN RISKS FOR CATHETER-DIRECTED THROMBOLYSIS** 
Event Category 
Event 
Cardiac 
Arrhythmia  
 
Right bundle branch block and complete heart block 
 
Hypotension 
Tricuspid and pulmonic valve damage 
Intimal disruption 
Wound 
Hematoma  
Peripheral vascular 
Vessel perforation 
Arterial dissection 
Arteriovenous fistula 
Thromboembolic episodes 
Thrombophlebitis 
Distal embolization 
Vessel spasm 
Venous 
Vascular thrombosis 
Cholesterol embolization 
Thromboembolism 
Cerebrovascular 
Intracranial hemorrhage  
Pulmonary 
Perforation of the pulmonary artery 
Pulmonary re-embolization 
Pulmonary edema 
Pleural effusion 
Pneumothorax 
Pulmonary infarct due to tip migration and spontaneous wedging, air 
embolism, and/or thromboembolism 
Miscellaneous 
Hemorrhage 
Contrast extravasation 
Pain and tenderness 
Sepsis/Infection 
Drug reactions 
Allergic reaction to contrast medium 
Orolingual angioedema 
Neurological deficits including stroke and death 
Amputation 
Death 

Inari Medical 
FlowTriever Retrieval/Aspiration System and CDT 
Version 4.0 
August 23, 2023 
 
 
 
 
 
 
PEERLESS Study (Protocol 21-002) 
CONFIDENTIAL 
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** From EKOS Endovascular System product brochure (PI-726201-AA), Label for Activase (Reference ID: 3702389), 
Uni-Fuse Product information (https://www.angiodynamics.com/about-us/risk-information)