Cook IVC Filter Study
Phase: NA
Conditions: Pulmonary Embolism
Sponsor: Cook Research Incorporated

Cook Research Incorporated  
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IVC Filter Study 
 
 
COMPANY CONFIDENTIAL 
CIP 12-018-10, Version Date 01 March 2018 
CLINICAL INVESTIGATION PLAN 
 
 
COOK IVC Filter Study 
 
 
Global Clinical Number 12-018 
 
 
Sponsor: 
 
 
Cook Research Incorporated 
 
 
 
 
 
 

Cook Research Incorporated
IVC Filter Study
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CLINICAL INVESTIGATION PLAN SIGNATURE PAGEO
CONTINUED
Co-Global Principal Investigator:
I hereby confirm that I approve of this Clinical Investigation Plan and agree to comply
with its terms as laid out in this document.
09 /1^AJ zot8
Date (DD Month YYYY)
iAO
Printed Name
Title
{L\^A C.F"ezr
COMPANY CONFIDENTIAL
CIP 12-018-10, Version Date 0l March 2018

Cook Research Incorporated  
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CLINICAL INVESTIGATION PLAN SIGNATURE PAGE, 
CONTINUED 
 
 
 
Principal Clinical Investigator: 
 
I hereby confirm that I approve of this Clinical Investigation Plan and agree to comply 
with its terms as laid out in this document. 
 
 
X 
 
 
 
     Signature 
 
  Date (DD Month YYYY) 
 
 
 
 
 
     Printed Name 
 
  Title 
 
 
 

Cook Research Incorporated  
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COMPANY CONFIDENTIAL 
CIP 12-018-10, Version Date 01 March 2018 
 
 
 
CONFIDENTIALITY STATEMENT 
 
 
 
This document shall be treated as a confidential document  
for the sole information and use of the  
clinical study team and the institution’s 
 Institutional Review Board/Ethics Committee/Research Ethics Board 
(IRB/EC/REB). 
 
 
 

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COMPANY CONFIDENTIAL 
CIP 12-018-10, Version Date 01 March 2018 
Table of Contents 
1.0 
Clinical Investigation Plan Overview ......................................................................9 
2.0 
Objective of the Clinical Study ..............................................................................11 
3.0 
Device Description and Intended Use ....................................................................11 
3.1 
General Device Description ........................................................................11 
3.2 
Indication for Use .......................................................................................12 
3.3 
Device Identification and Tracking ............................................................13 
3.4 
Instructions for Use ....................................................................................13 
4.0 
Literature Review...................................................................................................13 
5.0 
Risk Analysis and Risk Assessment ......................................................................20 
5.1 
Anticipated Benefits ...................................................................................20 
5.2 
Risks and Foreseeable Adverse Events and Adverse Device Effects ........21 
5.3 
Methods to Minimize Risks ........................................................................21 
6.0 
Design of the Clinical Study ..................................................................................22 
6.1 
Type/Design of Study .................................................................................22 
6.2 
Inclusion and Exclusion Criteria ................................................................22 
6.3 
Endpoints ....................................................................................................24 
6.3.1 Primary Effectiveness Endpoint .....................................................24 
6.3.2 Primary Safety Endpoint .................................................................24 
6.3.3 Secondary Endpoints ......................................................................24 
6.3.4 Rationale for Endpoints ..................................................................26 
6.4 
Variables to be Measured to Demonstrate Achievement of Endpoints ......26 
7.0 
Methods..................................................................................................................28 
7.1 
Patient Consent ...........................................................................................28 
7.2 
Point of Enrollment ....................................................................................28 
7.3 
Medications ................................................................................................28 
7.4 
Pre-procedure ..............................................................................................29 
7.5 
Filter Placement Procedure .........................................................................29 
7.6 
Post-Filter Placement/Pre-Discharge ..........................................................29 
7.7 
Post-Placement Follow-up ..........................................................................30 
7.8 
Filter Retrieval Procedure ...........................................................................31 
7.9 
Post-Retrieval Follow-up ............................................................................32 
7.10 
Duration of Study and Patient Participation ...............................................32 
7.11 
Imaging .......................................................................................................32 
7.12 
Criteria and Procedures for Withdrawal .....................................................32 
7.13 
Participation Endpoints of the Study ..........................................................33 

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8.0  
Statistical Considerations .......................................................................................33 
8.1 
Hypotheses to be Tested .............................................................................33 
8.1.1  Primary Effectiveness Hypothesis ..................................................33 
8.1.2  Primary Safety Hypothesis .............................................................34 
8.2 
General Statistical Analyses .......................................................................35 
8.3 
Sample Size ................................................................................................35 
8.4 
Missing Data ...............................................................................................36 
8.5 
Site-level Poolability ..................................................................................37 
8.6 
Limitations of the Study .............................................................................38 
9.0 
Deviations from Clinical Investigation Plan ..........................................................38 
10.0 
Data Collection and Reporting...............................................................................38 
10.1 
Electronic Case Report Forms ....................................................................38 
10.2 
Data Reporting ............................................................................................39 
11.0 
Data Management and Quality Assurance .............................................................39 
11.1 
Data Entry and Quality Assurance .............................................................39 
11.2 
Data Monitoring Arrangements ..................................................................40 
12.0 
Safety Monitoring and Procedures for Reporting Adverse Events ........................40 
12.1 
Safety Monitoring .......................................................................................40 
12.2 
Adverse Event Reporting ............................................................................40 
13.0 
Early Termination or Suspension of the Study ......................................................41 
14.0 
Ethical Considerations ...........................................................................................41 
15.0 
Publication Policy ..................................................................................................41 
16.0 
Clinical Study Administration and Investigators ...................................................42 
16.1 
Approvals and Agreements ........................................................................42 
16.2 
Investigators................................................................................................42 
16.3 
Insurance .....................................................................................................42 
17.0 
Study Timeline .......................................................................................................42 
18.0 
References ..............................................................................................................43 
 
Appendices  
A 
Contact Information 
B 
Written Procedures for Monitoring Studies 
C 
Definitions 

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CIP 12-018-10, Version Date 01 March 2018 
1.0 
Clinical Investigation Plan Overview 
The commercially available Günther Tulip® and Cook Celect® inferior vena cava filters 
have been previously evaluated in clinical studies.1-3  This prospective, multicenter, 
single-arm clinical study will further evaluate the safety and effectiveness of Cook’s 
permanent and retrievable inferior vena cava (IVC) filters (specifically, the Günther 
Tulip® and the Cook Celect® filters) in patients in need of temporary or permanent IVC 
filter placement for the prevention of pulmonary embolism (PE).  This study will enroll 
320 patients in the Celect® filter stratum and up to 150 patients in the Günther Tulip® 
stratum at up to 40 clinical sites globally; patients will be stratified based upon the type of 
filter they receive.  Consistent with current clinical practice and already-completed 
studies of Cook’s IVC filters, the study will evaluate the performance and safety of filters 
in patients considered at risk for PE for a variety of clinical reasons (i.e., a broad patient 
population).   
 
Study assessments will include, but are not limited to: rate of technical placement 
success, rate of freedom from new symptomatic PE, rate of freedom from new PE, rate of 
clinical perforation, rate of migration, rate of filter fracture, rate of filter embolization, 
rate of IVC thrombotic occlusion, rate of new symptomatic deep vein thrombosis (DVT; 
total incidence and new incidence), rate of procedure-related complications, time to filter 
retrieval, number of successful retrievals, and rate of technical retrieval success.   
 
Patients will be followed until 1 month after successful filter retrieval or until study 
completion 2 years after filter placement.  Enrollment is expected to be completed within 
2 years of initiating the study.  The primary study endpoints for the Celect® filter stratum 
will be compared to performance goals for safety (i.e., freedom from major adverse 
events) and effectiveness (i.e., technical placement success and freedom from new 
symptomatic PE while a filter is indwelling).  Additional study outcomes will be 
evaluated separately for each stratum (i.e., separately for patients receiving the Günther 
Tulip® and Celect® filters) and for the combined patient set.  The study flow diagrams are 
presented in Figure 1.1 (filter placement and follow-up) and Figure 1.2 (filter retrieval 
and follow-up). 
 
 

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aImaging performed to document the presence of PE in patients with suspected PE is to be collected 
bImaging performed pre-placement to verify anatomical study criteria and post-placement to verify the 
position of the filter  
cType of filter is at the discretion of the physician 
dX-ray may be substituted with high quality still shot from venacavagram (2-view) to assess device 
integrity 
Figure 1.1. Study flow diagram (filter placement and follow-up schedule) 
 
 
Baseline assessments and screening in accordance with institutional standard of carea 
Informed consent obtained 
Study-specific baseline assessments and screening to ensure the patient meets inclusion/exclusion 
criteria based on patient history, clinical assessment, duplex ultrasound (or other imaging as required to 
assess thrombus), and diagnostic imagingb 
Patient is enrolled in the study 
IVC filter placement (Günther Tulip® or Celect®)c and completion imagingb 
Pre-discharge: clinical assessment, X-ray (2-view device)d, and assessment of medications 
3-month follow-up: clinical assessment, assessment of continued need for filtration, and assessment of 
medications, hospitalizations, and medical conditions 
6-month follow-up: telephone contact and assessment of hospitalizations and medical conditions 
12-month follow-up: clinical assessment, assessment of continued need for filtration, abdominal CT 
with contrast, X-ray (2-view device)d, duplex ultrasound, and assessment of medications, 
hospitalizations, and medical conditions 
18-month follow-up: telephone contact and assessment of hospitalizations and medical conditions 
2-year follow-up: clinical assessment, assessment of continued need for filtration, abdominal CT with 
contrast, and assessment of medications, hospitalizations, and medical conditions 

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aX-ray may be substituted with high quality still shot from venacavagram (2-view) to assess device 
integrity  
 
Figure 1.2. Study flow diagram (filter retrieval and follow-up schedule) 
2.0 
Objective of the Clinical Study 
The objectives of this study are to further evaluate the safety and effectiveness of Cook’s 
commercially available IVC filters (specifically, the Günther Tulip® filter and the Cook 
Celect® filters) in patients in need of temporary or permanent IVC filter placement for the 
prevention of PE.  This study is intended to address FDA’s concerns related to IVC 
filters.4 
3.0 
Device Description and Intended Use 
3.1 
General Device Description 
All Cook vena cava filter sets include an IVC filter intended for prevention of recurrent 
PE in specific situations, such as chronic, recurrent PE where anticoagulant therapy has 
failed or is contraindicated.  All Cook vena cava filter sets are available in a femoral vein 
access version, with which the filter is introduced through the femoral vein, a jugular vein 
access version, with which the filter is introduced through the jugular vein, and a 
universal vein access version, which includes the components for both femoral and 
jugular vein approaches.  Each filter set consists of a preloaded filter, a coaxial introducer 
sheath system with a Check-Flo® valve, a hydrophilically coated pre-dilator, and a three-
way stopcock.   
The jugular and femoral vein access versions of all filters are available with the NavAlign 
introducer system (K090140), with design improvements to the introducer sheath and 
filter introducer intended to ease the filter placement procedure and reduce the likelihood 
of procedure-related complications. 
Pre-retrieval assessment: X-raya (2-view device) and venacavagram  
IVC filter retrieval and post-retrieval venacavagram 
1-month post-retrieval follow-up: clinical assessment and assessment of medications, 
hospitalizations, and medical conditions 

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The femoral vein access version of all filters is available with a flexible tip (composed of 
flexible stainless steel cable tubing covered with polyether block amide (PEBAX) shrink 
tubing) on the filter introducer, which is intended to make the tip more flexible to 
improve trackability of the introducer through the venous anatomy (K121057).   
The femoral vein access version of the Günther Tulip® filter and the Celect® filter is also 
available with added markers along the introducer sheath to improve visibility on 
procedural imaging (K112119).  In this set, the femoral introducer sheath is made of 
polyethylene (as compared to fluorinated ethylene propylene, which is the material 
component of the femoral introducer sheath for all other femoral vein access sets) and has 
an attached clip (composed of stainless steel spring wire with polycarbonate, 
acrylonitrile/butadiene/styrene (PC-ABS) handle) to mark the position of the sheath at the 
insertion site. 
The Celect® filter is available with added platinum markers on its primary legs to 
improve visibility on procedural imaging (K121629).  The femoral vein access version of 
the Celect® with platinum markers on its primary legs is only available with a flexible tip, 
and is not available with markers along its introducer sheath. 
Please reference the manufacturer’s Instructions for Use (IFU) for a complete description 
of each of these devices. 
3.2 
Indication for Use  
The Günther Tulip® filter and the Cook Celect® filters are intended for the prevention of 
recurrent PE via placement in the vena cava in the following situations:  
 
• Pulmonary thromboembolism when anticoagulant therapy is contraindicated; 
• Failure of anticoagulant therapy in thromboembolic diseases; 
• Emergency treatment following massive PE where anticipated benefits of 
conventional therapy are reduced; and 
• Chronic, recurrent PE where anticoagulant therapy has failed or is 
contraindicated. 
 
In addition to the specific labeled indications, it is well-documented in clinical practice 
guidelines that IVC filters have additional clinical indications, and are frequently placed 
in patients with the following: severe trauma, closed head trauma, spinal cord injury, 

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multiple long-bone or pelvic fractures, or other conditions putting them at high risk for 
PE (e.g., prolonged immobilization, pre-/post-operatively).5-8  Outcomes from use in 
these broad patient populations have been widely reported in the literature1-3,9-22, 
including those based on results of previous studies for the Cook IVC filters.1-3  Based on 
available data, patient outcome is not specifically related to indication for filter 
placement, but may be related to each patient’s overall medical condition, including the 
patient’s state of hypercoagulability, body mass index, use of anticoagulation, comorbid 
conditions, etc.  Moreover, Cook has conducted three previous studies of the performance 
of its permanent and retrievable IVC filters in a broad patient population,1-3 and the 
results (or interim results) of these studies are included in product labeling.  Furthermore, 
these broad patient populations were included in the indications for use that were 
approved in the PMA for the Cook Bird’s Nest® Vena Cava Filter (P850049). 
3.3 
Device Identification and Tracking  
As commercially available devices, the Cook IVC filters will be obtained by each site 
through normal commercial procurement methods and stored and accounted for 
following site-specific policies.  Lot numbers for devices used in study patients will be 
recorded on the appropriate Case Report Forms (CRFs). 
3.4 
Instructions for Use   
The manufacturer’s IFU for each filter contains the following information: 
 
• Complete instructions including storage and handling requirements, preparation 
for use, pre-use checks, precautions to be taken after use, and disposal.  
• Complete summary of the necessary training and experience required for use of 
these devices. 
• Complete description of the procedures involved in the use of these devices. 
4.0 
Literature Review 
Background 
Venous thromboembolism (VTE) affects nearly 1,000,000 people in the US each year, 
and includes both DVT and PE.  Pulmonary emboli commonly result from DVT.  PE is a 
major cause of morbidity and mortality in the US, with estimates of 400,000 – 630,000 
nonfatal PEs and 50,000 – 200,000 fatal PEs per year.8  Populations at an increased risk 

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for VTE include those with an inherited hypercoagulability, those undergoing complex 
surgery (including orthopedic surgery and bariatric surgery, among others), those with 
cancer, those with trauma, those with prolonged immobilization, those with a previous 
episode of VTE, as well as those patients with acute medical situations such as stroke, 
heart failure, respiratory failure, or infections.  The typical prevention method for VTE is 
anticoagulation therapy (e.g., heparin, warfarin).  However, anticoagulation may be 
contraindicated in some patients; for instance, those undergoing complex surgery, those 
with acute or recent bleeding, those with liver disease, and those with trauma.  Therefore, 
IVC filter placement via percutaneous access is frequently utilized to mitigate the 
potential risk of PE, either as an individual prevention modality or in combination with 
anticoagulation therapy.   
IVC filter placement is a well-established method for PE prophylaxis.  The first IVC 
filter was introduced in the late 1960s as an alternative to surgical ligation, caval 
plication, and clips.  The early filters (Mobin-Uddin Umbrella and Greenfield) required 
surgical cut-down for placement; Cook’s Bird’s Nest® Filter was the first percutaneously 
placed filter, and was approved under a PMA with expert advisory panel review.  All 
early filters (Mobin-Uddin Umbrella, Greenfield, Bird’s Nest®) were intended for 
permanent placement, i.e., the filters could not be retrieved after placement.  Filter 
technology has evolved to include a variety of percutaneously placed retrievable filters, 
which were initially developed in response to the following clinical observations: 1) a 
need for temporary periods of PE prophylaxis and 2) potential complications of 
permanently indwelling filters.  Retrievable filters may be retrieved or left as permanent 
devices; treatment is at the discretion of the physician, with specific considerations to the 
individual medical condition of each patient.  Cook’s Günther Tulip® filter has the 
longest history of permanent and retrievable use in the US, and Cook’s Celect® filter has 
also been used as a permanent and retrievable filter for many years.   
Despite the clinical rationale for the development of retrievable filters, in particular in 
periods of temporary high risk for PE (which includes patients with trauma and those in 
the perioperative setting, among others), the labeled filter indications do not adequately 
reflect use in the clinical studies performed to date or in routine clinical practice.  It 
should be noted that the expert panel recommended approval of the Bird’s Nest® for use 
in a broad population of patients considered at risk for PE, reflective of the clinical data 
supporting the filter and more appropriate than the current labeled indication (the 
indications were changed following a 1995 letter from FDA mandating that the product 

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indications for use be modified).  It is well-documented in clinical practice guidelines that 
IVC filter placement is widely utilized for both patients with proven VTE and patients 
without proven VTE but considered at high risk for VTE.5-8  Patients with VTE receive 
filters because 1) they are at high risk for PE and have a contraindication to or 
complication or failure of anticoagulation therapy or 2) they are at high risk for PE 
despite anticoagulation therapy, have increased risks of complications with 
anticoagulation therapy, or are noncompliant with anticoagulation therapy.  Patients 
without proven VTE receive filters when they are considered at risk for developing VTE 
and cannot receive effective prophylaxis or be monitored for the development of VTE 
(e.g., trauma patients, patients undergoing certain surgical procedures).  In each category, 
filters provide prophylactic protection against the occurrence of PE. 
Filter Efficacy 
Two randomized studies on the efficacy of IVC filters have been performed.  In the first, 
Decousus et al. randomized 400 patients with proximal DVT to permanent filter 
placement or no filter (patients were also assigned to two different anticoagulation 
regimens) and found that the filter group had significantly fewer events of PE (p=0.008), 
albeit more events of DVT (p=0.042) through 8 years.23,24  Specifically, the eight-year PE 
rates were 15.1% in the no filter group and 6.2% in the filter group.  More recently, 
Rajasekhar et al. randomized 34 trauma patients to retrievable filter (Celect®) placement 
or no filter and observed one PE in the no filter group and no PE in the filter group 
through 6 months.25  Thus, the randomized data available suggest that filters do provide 
protection against PE, as intended. 
In addition to these data, a wide body of clinical literature supports filter efficacy in a 
broad range of patient populations.  These include data from primarily single and 
multicenter studies of individual filter types, and some randomized studies comparing 
outcomes with different filter types.  Based on Cook’s ongoing analysis of the published 
literature, IVC filter use in a broad patient population is associated with a low PE rate (an 
average of 1.7%).2,3,11-13,19,21,23-41  This rate is much lower than that observed in the 
PREPIC study; moreover, this rate is lower than the expected PE rate in specific patient 
populations (for example, a literature review suggests that the PE rate in trauma patients 
without an IVC filter is approximately 4.9%).  In general, the data are supportive of the 
use of filters to prevent PE, though there are important covariates that may impact patient 
outcomes (e.g., history of VTE, anticoagulation scheme).   

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The benefit of filter placement in specific patient populations has also been discussed in 
the literature, including: 
• A recent systematic review of 24 studies describing filter placement in trauma 
patients, in which the authors concluded that (for the trauma population) filter-
related complications are infrequent (and those that do occur tend not to be 
clinically-significant) and that filter placement does reduce the incidence of PE 
and PE-related mortality.42 
• A recent assessment of the impact of IVC filters on in-hospital fatality due to PE 
based on the Nationwide Inpatient Sample using ICD-9-CM codes to identify 
patients with PE.  Results of the analysis suggested that IVC filter placement 
resulted in significantly fewer in-hospital fatalities in: 1) unstable patients with PE 
(regardless of the use of thrombolytic therapy; 33% vs. 51% in patients without 
thrombolytic therapy and 7.6% vs. 18% in patients with thrombolytic therapy; 
p<0.0001); and 2) stable patients receiving thrombolytic therapy (6.4% vs. 15%; 
p<0.0001).  The incidence of in-hospital fatality in stable patients not receiving 
thrombolytic therapy was also significantly reduced (7.2% vs. 7.9%; p<0.0001), 
though this reduction was not as clinically-meaningful as for the other 
populations.43 
Therefore, the clinical body of evidence supports filter placement for the prevention of 
PE in a broad range of patients. 
Filter Safety 
As with any medical implant, IVC filters are associated with a range of potential adverse 
events; these events are clearly outlined in Cook’s IFUs for its IVC filters.  Recent 
clinical practice guidelines report the incidence of adverse events for IVC filters in 
general to be as follows:7,8  

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Table 4.1.  Incidence of adverse events for IVC filters as a class 
Adverse Event 
Reported Rate 
IVC penetration 
0-41% 
Clinically-significant penetration 
0.4% 
Filter migration 
0-18% 
Filter fracture 
2-10% 
Recurrent PE 
0.5-6% 
Access site thrombus 
0-25% 
IVC occlusion 
2-30% 
Insertion problems 
5-23% 
 
These event rates are derived from events reported in the clinical literature, and are based 
on studies for various types of IVC filters and with a wide range of sample sizes (which 
directly impacts the reported event rates).  Moreover, definitions for the events vary 
among publications; in particular, they include both those that are clinically-significant 
(i.e., those associated with patient symptoms and/or requiring an intervention) and those 
without clinical consequences.  Therefore, the data should be interpreted carefully.  
In 2010, FDA issued a public notice in which it expressed concerns related specifically to 
the number of adverse event reports for filter migration, filter embolization, filter 
fracture, and perforation of the IVC;4 notably, event rates cannot be deduced from the 
FDA database of reported events.  In light of these concerns, FDA recommended that 
filter retrieval be considered as soon as the mechanical protection against PE is no longer 
warranted.  FDA’s recommendation is consistent with literature reports which suggest 
that patients may be at increased risk of adverse events when filters are left indwelling for 
extended periods of time; despite the fact that most filters are retrievable, a large 
percentage are left in place permanently.  Several publications have documented the fact 
that dedicated patient follow-up, with recurring assessment for continued risk of PE, 
results in increased rates of filter retrieval.44-47  These same authors postulate that 
increased filter retrieval rates may correlate to reduced incidence of filter complications.  
This hypothesis has yet to be verified in clinical studies, but some filter practices (both 
filter placement decisions and clinical follow-up practices) have changed in light of these 
safety concerns.  
Recently, the SVS/SIR physician working group presented what they consider to be the 
clinically-acceptable 1-year event rates for filter-related safety and effectiveness 

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outcomes (Table 4.2).  As detailed below, Cook’s IVC filter data is favorable in 
comparison to the rates in Tables 4.1 and 4.2.  Finally, these rates were utilized in the 
development of the performance goals and sample size for this study (described in further 
detail in Sections 8.1 and 8.3).   
Table 4.2.  Clinically-acceptable 1-year event rates48 
Adverse Event 
Acceptable 1-Year Rate 
Freedom from PE and procedural technical success 
90% 
Freedom from perforation, embolization, caval 
thrombosis/occlusion, DVT, major procedure related 
complications 
80% 
Caval Thrombosis/Occlusion 
< 5% 
Perforation 
< 2% 
DVT 
< 5% 
Embolization 
< 2% 
Fracture 
< 5% 
Migration 
< 4% 
Tilt 
< 5% 
PE 
< 2% 
 
Cook’s IVC Filter Data 
Cook Incorporated has sponsored three prospective, multi-center, single arm clinical 
studies of Cook IVC filters that are currently marketed in the US.  Briefly, these include 
the IDE study of 41 US patients treated with the Günther Tulip® filter (G000242; results 
of which supported a retrievable indication, cleared in K032426), a second study of 554 
US patients treated with the commercially available Günther Tulip® filter, and a study of 
129 OUS patients treated with the Celect® filter (interim results of which supported 
permanent and retrievable indications).  Results from all three studies have been 
published in peer-reviewed journals. 1-3  
All three studies evaluated filter safety and effectiveness (outcome measures similar to 
those listed in Tables 4.1 and 4.2) in patients at risk for developing a PE; as such, a 
variety of reasons for filter placement are captured in the studies.  Approximately half of 
the filter placements in these studies were associated with bariatric procedures or trauma 
cases; specifically, 28/41 patients (68.3%) in the IDE Günther Tulip® study, 329/554 
patients (59.4%) in the second Günther Tulip® study, and 53/129 patients (41.1%) in the 

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Celect® study received filters for these types of indications.  Mean follow-up duration 
(with range in parentheses) was 70.4 ± 49.3 (0-160) days for the IDE Günther Tulip® 
study, 124 ± 75.3 (3-494) days in the second Günther Tulip® study, and 277 ± 146 (1-
602) days in the Celect® study (note: the Celect® study included an arm specifically 
intended to assess permanent filters).  Mean filter indwell times (for retrieved filters) 
were 11.0 days in the IDE Günther Tulip® study, 58.9 days in the second Günther Tulip® 
study, and 179 days in the retrieval arm of the Celect® study.   
The significant safety findings (including PE and those AEs associated with the safety 
endpoint specified in this clinical investigation plan) in each study are summarized as 
follows.  In the Günther Tulip® IDE study, events included one filter misplacement and 
migration requiring immediate retrieval and placement of a new filter, one filter 
migration to the right atrium (with successful retrieval), one PE, one patient with a caval 
thrombosis/occlusion, and four deaths (none were device related); in addition, one patient 
had a vena cava injury following the retrieval procedure (with a normal 3-month post-
retrieval follow-up examination).  Events in the second Günther Tulip® study included 
five PEs, one DVT, one filter fracture noted at retrieval, one vascular access site 
complication following filter implant, and 13 deaths (two were related to PE and six were 
within 30 days of filter placement).  In the Celect® study, related events included two 
PEs, one DVT, one migration (without clinical sequelae), and 26 deaths (one associated 
with a PE and eight within 30 days of filter placement); there was no difference in the 
type of events observed in the permanent and retrievable study arms.  The incidence of 
each type of event observed in Cook’s clinical investigations is on the low end of, or 
below, the rates reported in Tables 4.1 and 4.2 above (Table 4.3).  Moreover, the overall 
rate of events associated with the primary endpoints of this clinical investigation (i.e., PE, 
placement success, caval thrombosis/occlusion, perforation with clinical sequelae, DVT, 
embolization, fracture, and migration) for the Günther Tulip® filter was 3.7% and the 
overall rate of events for the Celect® filter was 9.3%.   

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Table 4.3.  Cook’s IVC filter adverse event rates 
Outcome Measure 
Rate observed in Cook’s 
studies 
PE 
1.1% 
Placement success 
0.14% 
Caval thrombosis/occlusion 
0.14% 
Filter perforation with 
clinical sequelae 
0% 
DVT 
0.41% 
Embolization 
0% 
Fracture 
0.14% 
Migration 
0.28% 
 
Conclusion 
Many clinical studies have been conducted on IVC filters, including Cook’s studies of its 
Günther Tulip® and Celect® filters; Cook’s study results support the safety and 
effectiveness of its filters.  In light of FDA’s ongoing concerns regarding the use, 
performance, and safety of IVC filters, this study is intended to collect additional safety 
and effectiveness data on Cook’s IVC filters (i.e., the Günther Tulip® and Celect® filters) 
in patients in need of temporary or permanent IVC filter placement for prevention of PE.  
The study population and endpoints of interest are similar to those investigated in Cook’s 
previous IVC filter studies, to those of interest in the literature, and to those of interest to 
FDA4 and several physician society groups.49  Results of this study will be provided to 
FDA and may be used to support expanded indications for Cook’s IVC filters, and may 
also be compared to safety and effectiveness results associated with implantation of other 
filter types to the extent that this protocol is consistent with the PRESERVE study.   
5.0 
Risk Analysis and Risk Assessment 
5.1 
Anticipated Benefits 
Filter implantation may prevent or reduce the incidence of PE. 

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5.2 
Risks and Foreseeable Adverse Events and Adverse Device Effects 
The following foreseeable adverse events, which are captured in the IFUs of these 
commercially available devices, may be considered as potential risks to patients receiving 
a Cook IVC filter:  
• Damage to the vena cava  
• PE 
• Filter embolization (including embolization of fractured components) 
• Vena cava perforation/penetration  
• Vena cava thrombosis or occlusion 
• Hemorrhage 
• Hematoma at vascular access site 
• Infection at vascular access site 
• Cardiac tamponade 
• Filter malpositioning 
• Postphlebitic syndrome 
• Death 
• DVT  
In addition, participation in this clinical study is associated with the risk of additional 
radiation exposure from study imaging requirements that are above and beyond the 
standard of care.   
5.3 
Methods to Minimize Risks  
The Cook IVC filters will be used only by trained healthcare professionals who are 
experienced in the study procedure/treatment.  Patients will be selected in accordance 
with the inclusion/exclusion criteria outlined in this document.  
 
The imaging required as part of this clinical investigation has been recommended by 
FDA, in order to provide additional data for interpreting the occurrence of adverse 
events.  The risk of radiation exposure associated with study imaging has been minimized 
by collecting imaging data only where essential for the study or otherwise clinically 
indicated or per institutional standard of care. 
The device design, non-clinical testing, clinical study design, and the IFUs are intended 
to minimize the risks associated with the use of these devices.  The risks of the study 

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have been minimized and the potential benefits outweigh the risks in light of the 
importance of the knowledge to be gained about the safety and effectiveness of Cook’s 
IVC filters. 
6.0 
Design of the Clinical Study 
6.1 
Type/Design of Study 
This prospective, multicenter, single-arm clinical study will further evaluate the safety 
and effectiveness of Cook’s commercially available IVC filters (specifically, the Günther 
Tulip® and the Cook Celect® filters) in patients in need of temporary or permanent IVC 
filter placement for prevention of PE.  This study will enroll 320 patients in the Celect® 
filter stratum and up to 150 patients in the Günther Tulip® filter stratum at up to 40 
clinical sites globally.  At least half of the study patients in the Celect® filter stratum will 
be enrolled at US sites.  Consistent with current clinical practice, the study is expected to 
evaluate the performance and safety of filters in a broad range of patients considered at 
risk for PE (i.e., in patients considered at risk for PE for a variety of clinical reasons).  
This could include patients ranging from those with PE or DVT and a contraindication to, 
complication of, failure of, or poor compliance with anticoagulation to patients without 
evidence of PE or DVT, but considered to be at risk for PE for other reasons.   
 
The results of the study will be compared to safety (i.e., freedom from major adverse 
events) and effectiveness (i.e., technical placement success and freedom from new 
symptomatic PE while a filter is indwelling) performance goals. 
6.2 
Inclusion and Exclusion Criteria 
Patient eligibility for enrollment shall be based on known information at the time of the 
procedure.  Information obtained at a later date may contradict these criteria, but this will 
not be considered a violation of the CIP. 
 
Inclusion Criterion 
 
A patient may be suitable for inclusion in the study if he/she requires temporary or 
permanent IVC filter placement for the prevention of PE. 
 
 

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Exclusion Criteria 
 
Patients will be excluded from study enrollment if any of the following are true: 
 
General Exclusion Criteria 
1. Less than 18 years of age 
2. Patient or legally authorized representative is unable or unwilling to provide 
written informed consent prior to initiation of study procedures 
3. Unable or unwilling to comply with follow-up schedule 
4. Known hypersensitivity or contraindication to contrast medium that cannot be 
adequately premedicated 
5. Known allergy or sensitivity to cobalt, chromium, or nickel 
6. Pregnant or planning to become pregnant in the next 12 months  
7. Simultaneously participating in another investigational drug or device study in 
which the patient has not completed the follow-up phase for that study’s primary 
endpoint 30 days or more prior to being enrolled in this study 
8. Patient refuses blood transfusions 
 
Medical Exclusion Criteria 
9. Unable to tolerate the amount of contrast required by the procedure (in the 
opinion of the investigator) 
10. At risk of septic embolism 
11. Medical condition or disorder that would limit life expectancy to less than  
12 months or that may cause noncompliance with the protocol or confound the 
data analysis  
12. Existing IVC filter 
 
Anatomical Exclusion Criteria 
13. Duplicate IVC 
14. Anatomy that would prevent safe filter placement (e.g., condition of access 
vessels) 
15. IVC diameter > 30 mm or < 15 mm 

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6.3 
Endpoints 
6.3.1 Primary Effectiveness Endpoint 
The primary effectiveness endpoint is the rate of technical placement success and 12-
month freedom from new symptomatic PE while a filter is indwelling.  Analysis of the 
primary effectiveness endpoint will be performed separately for each filter type (i.e., each 
stratum).   
 
Events of symptomatic PE occurring after filter retrieval (i.e., through the 1-month post-
retrieval follow-up period) will be collected; such events will not count against the 
primary effectiveness endpoint, but will be reported as a secondary measure.   
6.3.2 Primary Safety Endpoint 
The primary safety endpoint is the rate of 12-month freedom from major adverse events.  
Major adverse events are defined as: clinical perforation, clinical migration, clinical 
fracture, embolization of the filter or filter fragments to the heart or lungs, IVC 
thrombotic occlusion, new symptomatic DVT while a filter is indwelling, access site 
complications with clinical sequelae, and procedure-/device-related death.  Analysis of 
the primary safety endpoint will be performed separately for each filter type (i.e., each 
stratum).  
 
Events occurring after filter retrieval (i.e., through the 1-month post-retrieval follow-up 
period) will be collected, but only the events of access site complications with clinical 
sequelae and procedure-related death will count against the primary safety endpoint.  
Other events (i.e., potentially new DVT without symptoms) will be reported as a 
secondary measure. 
6.3.3 Secondary Endpoints 
The secondary endpoints include: 
• Rate of technical placement success and 12-month freedom from new 
symptomatic PE while a filter is indwelling for the combined patient 
population 
• Rate of 12-month freedom from major adverse events for the combined 
patient population 

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• Rate of 12-month freedom from Grade 2 or Grade 3 filter leg interaction with 
the IVC, filter migration, filter fracture, and filter embolization for both the 
individual stratum and the combined patient population 
 
All primary and secondary endpoints will also be reported at 24 months.  In addition, 
analysis of the following secondary measures will be performed separately for each filter 
type (i.e., each stratum) and for the combined patient population: 
 
• Filter leg interaction with the IVC wall 
• Clinical perforation  
• Migration > 2 cm (including direction) 
• Symptomatic PE (occurring before and after filter retrieval) 
• PE (occurring before and after filter retrieval) 
• IVC thrombotic occlusion (occurring before and after filter retrieval) 
• Symptomatic DVT (occurring before and after filter retrieval) 
• DVT (total incidence and new incidence; occurring before and after filter 
retrieval) 
• Retroperitoneal hematoma 
• Hematoma at access site 
• Infection at access site 
• Thrombosis at access site 
• Death 
• Filter tilt (with measurement) 
• Filter fracture 
• Filter embolization 
• Filter deformation 
• Length of procedure (insertion and retrieval) 
• Length of ICU stay 
• Length of hospital stay 
• Technical placement success 
• Filter retrieval attempts 
• Technical retrieval success 
• Failed retrieval attempts, with reason for failed attempt 
• Retrieval-related complications 
• Adverse events occurring after filter retrieval 
• Delivery system performance 

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6.3.4 Rationale for Endpoints 
The endpoints were chosen as applicable measures of device safety and effectiveness 
because of their similarity to those of interest in the literature and to those of interest to 
FDA4 and several physician society groups.49 
6.4 
Variables to be Measured to Demonstrate Achievement of Endpoints 
Independent core laboratories (to be designated) will be used to provide detailed analysis 
of imaging data collected. 
 
The clinical data and imaging measurements will be collected on standardized case report 
forms (CRFs), which may serve as source documents.  The schedule for assessments is 
summarized in Table 6.1. 
 

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Table 6.1.  Data collection schedule 
Pre-procedurea 
Placement 
Post-procedureb 
3 months post-placement 
6 months post-placement 
12 months post-placement 
18 months post-placement 
2 years post-placement 
Pre-retrievalc 
Retrieval 
1 month post-retrieval  
Chest CT or other 
imaging to document 
pre-procedure PE in 
patients with clinical 
indications 
Xa 
 
 
 
 
 
 
 
 
 
 
Medical history 
Xd 
 
 
 
 
 
 
 
 
 
 
Clinical assessment 
Xd 
 
X 
X 
 
X 
 
X 
 
 
X 
Duplex ultrasound 
Xe 
 
 
 
 
X 
 
 
 
 
 
Diagnostic imaging 
 
Xf 
 
 
 
 
 
 
 
 
 
Venacavagram 
 
 
 
 
 
 
 
 
 
Xg 
 
Abdominal CT with 
contrast 
 
 
 
 
 
X 
 
X 
 
 
 
X-ray (2-view device) 
 
 
Xh,i 
 
 
Xi 
 
 
Xi 
 
 
Telephone contact 
 
 
 
 
X 
 
X 
 
 
 
 
aImaging to document PE (i.e., pulmonary arteriography, cross-sectional imaging, or ventilation/perfusion lung 
scan) in accordance with the institution’s standard of care; the imaging will be collected 
bPotential adverse events following filter placement must be documented by an appropriate imaging modality 
(e.g., suspected DVT should be assessed by bilateral lower extremity ultrasound and/or CT venography, 
suspected PE should be assessed by pulmonary arteriography, cross-sectional imaging, or ventilation/perfusion 
lung scan, and suspected perforation should be assessed by CT) 
cIf a 2-view device X-ray was collected within 30 days prior to retrieval, an additional X-ray would not be 
required pre-retrieval   
dCan be collected up to 6 weeks prior to the index procedure  
eDuplex ultrasound of the IVC, bilateral pelvic veins, and bilateral lower extremity veins.  For patients in whom a 
CT with contrast was performed as part of routine care within 2 weeks of the filter placement procedure, the CT 
may be used to assess for thrombus in vein segments visualized on CT.  For cases in which a physician feels it is 
in the best interest of the patient to forego the ultrasound exam so the filter may be placed immediately and/or in 
which a duplex ultrasound may not be physically possible prior to filter placement (e.g., patients with trauma to 
the pelvis), the venogram may be used to assess for thrombus in vein segments visualized on the venogram.  If 
segment(s) of vein are not assessed before the filter is placed, assessments are to be completed within one day 
after the placement procedure.  Assessments of all vein segments of interest are to be completed, unless a 
patient’s injuries prevent examination of one or more vein segment(s) 
fImaging performed pre-placement to verify anatomical study criteria and post-placement to verify the position of 
the filter  
gVenacavagram performed pre- and post-retrieval 
hPatients undergoing bedside filter placement in whom a 2-view device X-ray could not be obtained prior to 
discharge must have a 2-view device X-ray within 45 days post-placement 
i2-view device X-ray may be substituted with high quality still shot from venacavagram (2-view) to assess device 
integrity  
 

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6.5 
Measures to be Taken to Avoid or Minimize Bias 
This study is designed as a prospective clinical trial to minimize bias in analyzing the 
results.  Specifically, the study will utilize event adjudication by an independent clinical 
events committee and imaging analysis by a centralized core laboratory to minimize bias 
in analyzing the results.  Patients requiring temporary or permanent IVC filter placement 
to prevent PE will be screened consecutively to mitigate selection bias.  Investigational 
sites will maintain a screening log of patients; for patients who are excluded from the 
study, the log will indicate the primary inclusion/exclusion criterion that is violated.  A 
single institution may enroll up to 20% of the patients in each stratum to minimize bias 
that may be introduced if the majority of patients are enrolled from one or two large 
clinical sites.  Finally, filter choice will be left to the discretion of the physician. 
7.0 
Methods 
7.1 
Patient Consent 
Patients who meet the inclusion criterion and none of the exclusion criteria will be invited 
to participate in this study.  All patients eligible for entry into the study will have the 
study explained to them, as well as potential risks and benefits of their participation in the 
study.  Each patient (or legally authorized representative) who agrees to participate will 
be required to sign an informed consent document prior to undergoing study-specific 
testing or the filter placement procedure.  If new information is obtained after a patient 
receives treatment with the device, patients who have not exited the study will be 
informed about the new information, and will be reconsented at the discretion of the 
investigators and/or the sites’ IRBs/ECs/REBs. 
7.2 
Point of Enrollment 
Patients will be considered enrolled in the study once the filter introducer sheath is 
inserted below the skin. 
7.3 
Medications 
Patients should receive medication(s) according to the institution’s standard of care 
and/or at the physician’s discretion, based on each patient’s individual medical condition. 
The use of antiplatelet and anticoagulation medications should be recorded on 
appropriate CRFs. 

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7.4 
Pre-procedure 
A pre-procedure clinical assessment will be completed (up to 6 weeks prior to the index 
procedure) including documentation of medical comorbidities and assessment of 
medications.  Duplex ultrasound of the IVC, bilateral iliac veins, and bilateral lower 
extremity veins will be performed; presence of DVT will be documented on the 
appropriate CRF.  For patients in whom a CT with contrast was performed as part of 
routine care within 2 weeks of the filter placement procedure, the CT may be used to 
assess for thrombus in vein segments visualized on CT.  For cases in which a physician 
feels it is in the best interest of the patient to forego the ultrasound exam so the filter may 
be placed immediately and/or in which a duplex ultrasound may not be physically 
possible prior to filter placement (e.g., patients with trauma to the pelvis), the venogram 
may be used to assess for thrombus.  If segment(s) of vein are not assessed before the 
filter is placed, assessments are to be completed within one day after the placement 
procedure.  Assessments of all vein segments of interest are to be completed, unless a 
patient’s injuries prevent examination of one or more vein segment(s).   
 
Patients with suspected PE should undergo appropriate assessment for the presence of 
PE, including appropriate imaging (i.e., pulmonary arteriography, cross-sectional 
imaging, or ventilation/perfusion lung scan), according to the institution’s standard of 
care.  This imaging will be collected and results of these assessments will be documented 
on the appropriate CRF.   
7.5 
Filter Placement Procedure 
• Diagnostic imaging will be performed prior to study enrollment to verify 
anatomical study criteria.     
• Only one Cook IVC filter should be placed in each patient.  The Cook IVC filter 
should be implanted in accordance with the respective IFU (i.e., caudal to the 
renal veins).   
• Completion imaging will be performed to assess filter position (including tilt) and 
to assess the vena cava for evidence of injury. 
7.6 
Post-Filter Placement/Pre-Discharge 
Post-placement care includes observation and discharge according to institutional 
standard of care and completion of clinical and medication assessments.  In addition, a 2-

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view device X-ray will be performed prior to hospital discharge; the X-ray should be 
performed in AP and LAT views.  Patients undergoing bedside filter placement in whom 
a 2-view device X-ray could not be obtained prior to discharge must have a 2-view 
device X-ray within 45 days post-placement. 
7.7 
Post-Placement Follow-up 
Follow-up windows are intended as guidelines only.  They are not absolute and are not 
intended to limit data collection due to scheduling conflicts. 
 
• 3 Months Post-Placement (90 ± 15 days): Office visit including an assessment of 
the need for continued filtration, and an assessment of medications, 
hospitalizations, and medical conditions. 
 
• 6 Months Post-Placement (180 ± 30 days):  Telephone contact by the clinical site 
to assess hospitalizations and medical conditions.  Up to three attempts should be 
made to contact the patient. 
 
• 12 Months Post-Placement (365 ± 30 days): Office visit including an assessment 
of the need for continued filtration, and an assessment of medications, 
hospitalizations, and medical conditions.  An abdominal CT with contrast to 
assess filter leg interaction with the IVC, a 2-view device X-ray to assess device 
integrity (the X-ray should be performed in AP and LAT views), and duplex 
ultrasound (IVC, bilateral pelvic veins, and bilateral lower extremity veins) to 
assess thrombus/DVT will be performed. 
 
• 18 Months Post-Placement (540 ± 60 days):  Telephone contact by the clinical 
site to assess hospitalizations and medical conditions.  Up to three attempts should 
be made to contact the patient. 
 
• 2 Years Post-Placement (730 ± 60 days): Office visit including an assessment of 
the need for continued filtration, and an assessment of medications, 
hospitalizations, and medical conditions.  An abdominal CT with contrast to 
assess filter leg interaction with the IVC will be performed. 
 

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The need for continued filtration will be assessed based on each patient’s overall medical 
condition.  The decision to proceed to a retrieval attempt should also be based on factors 
such as the patient’s ability and willingness to undergo the retrieval procedure and the 
physician’s assessment of the risk/benefit ratio associated with the retrieval procedure. 
If at any time during follow-up a patient presents with adverse clinical symptoms 
potentially related to his/her indwelling filter or the development of DVT/PE, appropriate 
assessments and treatment should be conducted according to the institution’s standard of 
care.  Clinical and imaging findings will be documented on the appropriate CRFs.  For 
example: 
• If the physician suspects a vena cava perforation, an abdominal CT with contrast 
will be performed to assess filter leg interaction with the IVC. 
• If the physician suspects DVT, the DVT will be documented by duplex 
ultrasound, contrast venography, CT, or MR venography. 
• If the physician suspects PE, the PE will be documented by pulmonary 
arteriography, cross-sectional imaging (e.g., CT, MRI), or ventilation/perfusion 
lung scan. 
7.8 
Filter Retrieval Procedure 
The Cook IVC filters may be retrieved if clinically indicated. 
 
Before retrieval, the following will be performed: 
• Two-view device X-ray to assess device integrity; X-ray should be performed in 
AP and LAT views; and 
• Venacavagram to assess filter position, presence and extent of thrombus in the 
filter, and IVC wall morphology. 
 
If a 2-view device X-ray was collected within 30 days prior to retrieval, an additional pre-
retrieval X-ray would not be required.  The venacavagram will be collected procedurally, 
just prior to filter retrieval.  
Filter retrieval should not be attempted in the instance that significant trapped thrombus 
(i.e., > 25% of the cone volume) is observed in the filter.  Filter retrieval should be 
performed using the Günther Tulip® Retrieval Set and in accordance with the IFU.  
Following retrieval, the IVC will be assessed by venacavagram. 

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If the filter retrieval attempt is unsuccessful, the patient will continue his/her post-
placement follow-up schedule, indexed to the filter placement procedure.  Another filter 
retrieval attempt can be made at a later date, depending on the patient’s medical 
condition. 
7.9 
Post-Retrieval Follow-up 
If the filter retrieval attempt is successful, the patient will assume the post-retrieval 
follow-up schedule.  Follow-up windows are intended as guidelines only.  They are not 
absolute and are not intended to limit data collection due to scheduling conflicts. 
 
• 1 Month Post-Retrieval (30 ± 15 days):  Office visit including an assessment of 
medications, hospitalizations, and medical conditions. 
 
Suspected PE post-retrieval must be objectively confirmed by imaging (i.e. pulmonary 
arteriography, cross-sectional imaging, or ventilation/perfusion lung scan) or at autopsy 
and will not count against the primary endpoint. 
7.10 
Duration of Study and Patient Participation 
Patients will be followed until 1 months after successful filter retrieval or until study 
completion 2 years after filter placement.  Total study duration (from study initiation 
through patient enrollment and follow-up) is expected to be less than 5 years. 
7.11 
Imaging 
An imaging manual will be provided by the sponsor.  The imaging criteria specified in 
the manual should be followed for all imaging required per this CIP.  Any imaging 
performed at pre-procedure, filter placement, filter retrieval, or at any time during follow-
up to evaluate potential adverse events will be recorded on the appropriate CRF and 
submitted to the data coordinating center. 
7.12 
Criteria and Procedures for Withdrawal 
A patient may decide to withdraw from the study at any time without prejudice or loss of 
care.  The patient should notify the investigator of his/her desire to withdraw.  The 
investigator will notify the sponsor.  The investigator may also decide to withdraw a 

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patient from the study at any time based on medical judgment.  In all instances of 
withdrawal, data collected up to the time of patient withdrawal, including the study exit 
form, should be submitted to the data coordinating center, and should include the reason 
why the patient has been withdrawn from the study.  Patients withdrawn from the study 
should be followed according to institutional standard of care.   
 
In the event a patient cannot be contacted for post-treatment assessments, at least three 
attempts should be made to contact the patient, and these efforts should be documented 
on the appropriate CRF.  If a patient misses post-treatment assessments and cannot be 
located, a lost to follow-up entry should be submitted. 
7.13 
Participation Endpoints of the Study 
A patient’s participation in the study will end after any of the following: 
• Completion of all scheduled clinical and imaging evaluations to 1 month post-
retrieval or 2 years post-placement; 
• Device not implanted; 
• Patient withdrawal or lost to follow-up; 
• Closure of the study; or 
• Patient death. 
Any data collected on the patient up to a participation endpoint (or until all queries 
involving the patient are resolved) may be used in the study. 
8.0  
Statistical Considerations 
8.1 
Hypotheses to be Tested 
The study hypotheses will be tested only for patients receiving Celect® filters.  No formal 
hypotheses will be tested for patients receiving the Günther Tulip® filter; rather, summary 
statistics will be presented for patients receiving the Günther Tulip® filter. 
8.1.1  Primary Effectiveness Hypothesis 
The primary effectiveness endpoint is the rate of technical placement success and 12-
month freedom from new symptomatic PE while a filter is indwelling.  The analysis 
requires that the performance goal of 90% be met for technical placement success and 
freedom from new symptomatic PE at 12 months while a filter is indwelling.  The 

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performance goal was derived based on what are considered clinically acceptable rates 
for technical placement success and new symptomatic PE in the overall population.48  
The performance goal will be said to have been met provided the null hypothesis is 
rejected in favor of the alternative with a one-tailed exact binomial test at the 0.025 level.  
The hypothesis will be tested only for patients receiving Celect® filters.  Given that π is 
the probability that a randomly selected patient did not experience any technical 
placement failure or new symptomatic PE within 12 months while a filter is indwelling, 
the null and alternative hypotheses are as follows. 
Null Hypothesis: The rate of technical placement success and 12-month freedom from 
new symptomatic PE while a filter is indwelling, π, does not meet the performance goal 
(90%). 
 
H0: π ≤ 90% 
Alternative Hypothesis: The rate of technical placement success and 12-month freedom 
from new symptomatic PE while a filter is indwelling, π, meets the performance goal 
(90%). 
 
Ha: π > 90%  
8.1.2  Primary Safety Hypothesis 
The primary safety endpoint is the rate of 12-month freedom from major adverse events.  
Major adverse events are defined as: clinical perforation, clinical migration, clinical 
fracture, embolization of the filter or filter fragments to the heart or lungs, IVC 
thrombotic occlusion, new symptomatic DVT while a filter is indwelling, access site 
complications with clinical sequelae, and procedure-/device-related death.  The analysis 
requires that the performance goal of 80% be met for freedom from major adverse events 
at 12 months.  The performance goal was derived based on what are considered clinically 
acceptable rates for each complication in the overall population.48 
 
The null (H0) and alternative (HA) hypotheses are expressed as follows: 
 
 
H0:  S(t) ≤ 80% 
 
Ha:  S(t)  > 80% 
 

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where:  
• t is time through 12 months  
• S(t) is the true rate of freedom from major adverse events at time t.  
 
The hypothesis will be assessed using a Z-statistic. The Z-statistic is given by  
 
 
 
Z = (𝑆̂(𝑡) – 0.8)/SE 
 
where: 
 
• 𝑆̂(𝑡) = Kaplan-Meier estimate of freedom from major adverse events 
(S(t)) at 12 months 
• SE = Standard Error =V(S(t)) , where 𝑉̂(𝑆̂(𝑡)) is the estimate of the 
variance of the Kaplan-Meier estimate using the methods described by 
Peto et al.50 
 
The performance goal will said to have been met provided the null hypothesis is rejected 
in favor of the alternative if 𝑆̂(𝑡) −0.8 > ZαSE , for α = 0.025.  The hypothesis will be 
tested only for patients receiving Celect® filters.  
8.2 
General Statistical Analyses 
Statistical analysis will be performed using SAS® for Windows® (release 9.3 or higher) or 
other widely accepted statistical software.  Clinically-relevant baseline variables will be 
tabulated by each stratum.  Continuous variables will be reported as means and standard 
deviations unless otherwise noted.  Categorical variables will be reported as percent.  
Unadjusted 95% confidence intervals will be presented for the secondary endpoints, with 
a footnote specifying that they are unadjusted.  Survival analysis techniques such as 
Kaplan-Meier or Cox Proportional Hazards will be incorporated if censoring of data 
occurs. 
8.3 
Sample Size 
The study is designed to enroll 320 patients in the Celect® filter stratum (to evaluate the 
safety and effectiveness hypotheses) and up to 150 patients in the Günther Tulip® filter 
stratum at up to 40 sites globally.  At least half of the study patients in the Celect® filter 
stratum will be enrolled at US sites. 
 
For the primary effectiveness endpoint, based on what are considered clinically 
acceptable rates for technical placement success and new symptomatic PE in the overall 

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population, a performance goal of the rate of technical placement success and 12-month 
freedom from new symptomatic PE while a filter is indwelling was established to be 
90%.48  Additionally, based on the data from previous Cook sponsored studies (as 
summarized in Section 4.0), the rate of technical placement success and 12-month 
freedom from new symptomatic PE while a filter was indwelling was estimated to be 
98.4% for the Celect® filter stratum.  A sample size of 70 patients will be required to 
assess the primary effectiveness hypothesis for the Celect® filter stratum, with a one-
sided exact binomial test, at a type I error rate of 0.025, and a power of 0.9.  The 
calculation was performed with the SAS UnifyPow macro. 
 
For the primary safety endpoint, based on what are considered clinically acceptable rates 
for each complication in the overall population, a performance goal of the rate of 12-
month freedom from major adverse events was established to be 80%.48  Based on the 
data from previous Cook-sponsored studies (as summarized in Section 4.0), the rate of 
12-month freedom from major adverse events was estimated to be 92.2% for the Celect® 
filter stratum.  A sample size of 88 patients will be required to assess the primary safety 
hypothesis for the Celect® filter stratum, with a one-sided exact binomial test, at a type I 
error rate of 0.025, and a power of 0.9.  The calculation was performed with the SAS 
UnifyPow macro. 
 
Based on sample size calculations, a minimum of 88 patients in the Celect® filter stratum 
will be required to evaluate the safety and effectiveness endpoints.  Cook intends to 
enroll 320 patients in the Celect® filter stratum; this sample size allows for an attrition 
rate of 72% (i.e., 60% of filters to be retrieved prior to 12 months and an additional 12% 
of patients who may die, withdraw, or become lost to follow-up).  The study may also 
enroll up to 150 patients in the Günther Tulip® filter stratum. 
8.4 
Missing Data 
If the amount of missing data does not result in a reduction of analyzable patients to a 
number that is below that which is required for sufficient statistical power of the primary 
endpoints, case deletion will be the primary method to handle missing data.   
 
However, if missing data results in a reduction of analyzable patients to a number that is 
lower than what is required for sufficient statistical power of the primary measures, then 
missing data will be addressed using multiple imputation with best available data, if 

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appropriate.  This method will be used to predict missing endpoint and imaging data.  
Previous clinical trial experience suggests that some portion of the imaging data may not 
meet the criteria for accurate review by the core laboratory; however, it is recognized that 
the investigator uses this information to provide the best possible care for the patient.  
Therefore, it is reasonable to substitute any missing core laboratory measurements with 
the corresponding measurements made by the investigator or institutional staff. 
 
Statistical imputation strategies originating from Schafer may also be used, supplemented 
with notes provided by Shafer.51,52  All missing endpoint and covariate data will be 
imputed with the values simulated from their respective empirical distributions.  The 
computations (with no covariates) will be performed using five imputed datasets and 
PROC MI and PROC MIANALYZE in SAS version 9.3, or WinBUGS 1.4 or later.  
Unless evidence suggests otherwise, missing at random data will be assumed. 
 
Additional analyses may also be performed to address missing data, including tipping 
point analysis. 
8.5 
Site-level Poolability 
At the final analysis, poolability of data from multiple sites will be verified by examining 
the primary safety and effectiveness endpoints using logistic regression models.  Site-
level poolability will be considered appropriate provided that these measures are similar 
among sites. 
 
It is expected that some sites may have too few patients to provide reasonable site-level 
estimates of the primary measures.  Each investigative site will be allowed to enroll no 
more than 20% of the patients in each stratum to ensure the overall results are not biased 
by the results from a single site.  Pooling of this information will be explored based on 
hospital size (large versus small, determined based on number of beds and annual number 
of discharges), site enrollment (large versus small), type of hospital (community versus 
teaching), and other group-wise strategies. 
 
It is recognized that patient baseline characteristics may differ among sites, with some 
sites routinely treating specific patient types (e.g., trauma patients).  It is anticipated that 
the primary endpoint measures may be related to covariates that reflect this.  Thus, 
observed site-specific differences among the primary endpoints will be checked for 

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confounding with other measured covariates (e.g., age, sex).  This can be accomplished 
using logistic regression models that include site and other measured covariates as 
independent variables. 
 
Should one or more sites be found to differ significantly from the rest, then logistic 
regression analysis will be performed with an intercept term and a covariate to 
distinguish between the unusual site(s) and those sites that are considered poolable. 
Analysis on the primary endpoints will be performed by constructing 95% confidence 
interval on odds ratio for the intercept term. 
8.6 
Limitations of the Study 
All patients will be required to meet the inclusion/exclusion criteria specified in this 
document, which may limit the overall range of patients to which inferences may be 
applied.  Additionally, this study is not designed to provide data beyond 2 years after 
filter placement or beyond 1 month after filter retrieval. 
9.0 
Deviations from Clinical Investigation Plan 
Investigators are not allowed to deviate from this CIP without prior authorization by the 
sponsor except under emergency situations when necessary to preserve the rights, safety, 
or well-being of study patients. 
 
Deviations (failures to follow requirements of the CIP) and noncompliances (failures to 
follow applicable regulations) will be recorded together with an explanation.  Deviations 
or noncompliances that impact the rights, welfare, or safety of patients shall be promptly 
reported to the sponsor and IRB/EC/REB as required. 
 
If appropriate, corrective and preventive actions will be discussed by the sponsor, 
investigator, and/or the IRB/EC/REB to determine a suitable course of action.  
10.0 
Data Collection and Reporting 
10.1 
Electronic Case Report Forms 
Patient data will be collected and entered by trained personnel at the clinical site onto 
electronic Case Report Forms (eCRFs) through an Electronic Data Capturing (EDC) 
system.  This is a secure, web-based system, allowing those with permission to access 

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data from any location at any time.  Source data are to be retained for data entered into 
the eCRF system.  Data obtained and simultaneously entered into the EDC system may 
also serve as source documentation.  Worksheets created from the eCRF are available to 
each site and may serve as source documentation (e.g., 18-month telephone follow-up).  
Site personnel are required to undergo data entry training and will have unique login 
names and passwords in order to enter patient data.  In accordance with 21 CFR Part 11, 
the eCRF system creates a secure, computer-generated, time stamped audit trail to record 
the date and time of operator entries and actions that create, modify, or delete electronic 
records. 
10.2 
Data Reporting 
Progress reports will be submitted to FDA every 6 months for the first 2 years of the 
study and annually thereafter, from the date that this CIP is approved by FDA.  A final 
report will be submitted to FDA no later than three months after study completion (i.e., 
after the last patient completes their last follow-up visit).  In the event the study is 
terminated prior to completion, a final report will be submitted to FDA no later than three 
months after study termination.   
 
Also, as required by local regulations, progress reports and a final report at the conclusion 
of the clinical study will be submitted by the investigators and sponsor to the regulatory 
authorities and/or IRB/EC/REB. 
11.0 
Data Management and Quality Assurance 
11.1 
Data Entry and Quality Assurance 
Each principal investigator or appropriately trained designee shall enter the clinical data 
into the electronic data capture system on standardized CRFs.  Investigators will provide 
all applicable clinical data and documentation to the sponsor.  Patient data and documents 
pertaining to the study will be kept and archived by the sponsor.  Data will be reviewed 
for missing data, data consistency, and reasonableness of responses.  Discrepancies will 
be resolved through a formal query process involving direct contact with investigators or 
research coordinators.  The data coordinating center is responsible for database 
management, data verification, data archiving, and data retention. 
 

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As needed to assist the sponsor in its research (e.g., during evaluation of an adverse 
event), data will be accessible to the sponsor, the participating investigators, the 
manufacturer, and companies or individuals the sponsor authorizes. 
11.2 
Data Monitoring Arrangements 
The conduct of the clinical study will be supervised through a process of remote and on-
site monitoring.  The data coordinating center will remotely monitor the study for data 
completeness and for adverse events.  On-site monitoring will be implemented as 
necessary throughout the course of the study.  The investigator/institution will provide 
direct access to source data/documents for study-related monitoring, audits, IRB/EC/REB 
review, and regulatory inspection.  Written procedures for monitoring the study are 
maintained by the data coordinating center and are summarized in Appendix B. 
12.0 
Safety Monitoring and Procedures for Reporting Adverse Events 
12.1 
Safety Monitoring 
An independent Clinical Events Committee (CEC) consisting of physicians, who are not 
investigators in the study and who do not have a perceived conflict of interest with the 
conduct and administration of the study, will be established to adjudicate clinical events 
reported during the study.  This adjudication will be performed to assess whether the 
events were due to a pre-existing or unrelated condition, or were procedure-related, 
technique-related, and/or device-related. 
 
A central core laboratory will be used for image analysis to provide uniformly defined 
analysis of images. 
 
Regularly scheduled reviewing/monitoring of all patient data will be conducted at the 
data coordinating center, in part, for identification of adverse events and assurance that 
they are correctly reported to the CEC.   
12.2 
Adverse Event Reporting 
Adverse events are to be reported to the data coordinating center using the appropriate 
CRF.  In cases of serious adverse events or adverse device effects (i.e., adverse event 
with relation to the study device), completed forms should be submitted to the data 
coordinating center as soon as possible upon knowledge of the event. 

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The data coordinating center will review the information submitted for possible reporting 
to the sponsor.  The sponsor shall, if required according to applicable regulations, report 
the event to the appropriate regulatory authority.  The principal investigator or designee 
will notify his/her IRB/EC/REB of applicable events according to institutional guidelines.  
Investigators and clinical sites will be notified of applicable events by the sponsor, as 
appropriate. 
13.0 
Early Termination or Suspension of the Study 
Any decision to suspend enrollment or terminate the study, either completely or at one or 
more sites, will be made by the sponsor and, if appropriate, the local IRB/EC/REB.  If a 
decision is made to terminate the study, all patients will be followed according to 
institutional standard of care.  
14.0 
Ethical Considerations 
This clinical study will be conducted in accordance with the ethical principles that have 
their origin in the Declaration of Helsinki and in accordance with global regulations 
including ISO 14155, ICH GCP, and 21 CFR 812. 
 
The investigator is responsible for obtaining approval of this clinical study from the 
relevant IRB/EC/REB at his/her associated institution.  The study will not begin until a 
favorable opinion of the IRB/EC/REB has been obtained.  The investigator is responsible 
for complying with requirements imposed by their IRB/EC/REB and/or regulatory 
authority.  Furthermore, the investigator will ensure that local regulations concerning data 
protection are followed. 
15.0 
Publication Policy 
Publication policy, rights, and obligations for this study have been negotiated, detailed, 
and defined in the study’s contractual documents with the clinical site and investigators. 

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16.0 
Clinical Study Administration and Investigators 
16.1 
Approvals and Agreements 
The sponsor, national principal investigator(s), and the principal clinical investigators for 
each clinical site shall agree to this document and any modifications.  A justification for 
any modifications will be documented.  Approval and agreement will be indicated by 
signing the signature page provided with this document. 
16.2 
Investigators 
To see a complete list of the sponsor, manufacturer, monitor, and data coordinating center 
along with their contact information, please refer to Appendix A.  A complete list of the 
national principal investigator(s), principal clinical investigators, and coordinating 
clinical investigators, along with their qualifications and contact information, will be 
maintained by the data coordinating center.  Names and addresses of all clinical sites and 
other institutions involved in the clinical study (e.g., core labs) will also be maintained by 
the data coordinating center. 
16.3 
Insurance 
Insurance for the study will be obtained by the sponsor prior to patient enrollment. 
17.0 
Study Timeline 
Table 17.1 projects the study timeline. 
Table 17.1.  Study timeline  
Estimated date of study initiation (at least one 
site with IRB/EC/REB approval, contract 
signed, and site training/initiation) 
Prior to completion of the second 
quarter of 2014 
Estimated monthly number of study sites with 
IRB approvals 
1 
Expected date of initiation of subject 
enrollment 
Prior to completion of the second 
quarter of 2014 
Estimated number of subjects enrolled per 
month 
2 per active site 
Estimated date for subject enrollment 
completion 
18-30 months after all sites are eligible 
to enroll 

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Expected date to complete follow-up of all 
study participants 
Approximately 24 months after the last 
patient is enrolled 
Expected date for final report submission 
3 months after study completion (i.e., 
after the last patient completes their last 
follow-up visit) 
18.0 
References 
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Günther Tulip filter retrievability multicenter study including CT follow-up: final report. 
J Vasc Interv Radiol. 2006;17:1017-1023. 
2. Smouse HB, Rosenthal D, Thuong VH, Knox MF, Dixon RG, Voorhees WD 3rd, et al. 
Long-term retrieval success rate profile for the Günther Tulip vena cava filter.  J Vasc 
Interv Radiol. 2009;20:871-877. 
3. Lyon SM, Riojas GE, Uberoi R, Patel J, Lipp ME, Plant GR, et al. Short- and long-
term retrievability of the Celect vena cava filter: results from a multi-institutional 
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4. US Food and Drug Administration. “Removing retrievable inferior vena cava filters: 
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Development of a research agenda for inferior vena cava filters: proceedings from a 
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8. Caplin DM, Nikolic B, Kalva SP, Ganguli S, Saad WE, Zuckerman DA.  Quality 
improvement guidelines for the performance of inferior vena cava filter placement for the 
prevention of pulmonary embolism.  J Vasc Interv Radiol. 2011;22:1499-1506. 
9. Paton BL, Jacobs DG, Heniford BT, Kercher KW, Zerey M, Sing RF.  Nine-year 
experience with insertion of vena cava filters in the intensive care unit.  Am J Surg. 
2006;192:795-800. 
10. Oliva VL, Perreault P, Giroux MF, Bouchard L, Therasse E, Soulez G.  Recovery G2 
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11. Given MF, McDonald BC, Brookfield P, Niggemeyer L, Kossmann T, Varma DK, et 
al.  Retrievable Gunther Tulip inferior vena cava filter: experience in 317 patients.  J Med 
Imaging Radiat Oncol. 2008;52:452-457. 
12. Ziegler JW, Dietrich GJ, Cohen SA, Sterling K, Duncan J, Samotowka M.  PROOF 
trial: protection from pulmonary embolism with the OptEase filter.  J Vasc Interv Radiol. 
2008;19:1165-1170. 
13. Pellerin O, Barral FG, Lions C, Novelli L, Beregi JP, Sapoval M.  Early and late 
retrieval of the ALN removable vena cava filter: results from a multicenter study.  
Cardiovasc Intervent Radiol. 2008;31:889-896. 
14. Doody O, Given MF, Kavnoudias H, Street M, Thomson KR, Lyon SM.  Initial 
experience in 115 patients with the retrievable Cook Celect vena cava filter.  J Med 
Imaging Radiat Oncol. 2009;53:64-68. 
15. Sangwaiya MJ, Marentis TC, Walker TG, Stecker M, Wicky ST, Kalva SP.  Safety 
and effectiveness of the Celect inferior vena cava filter: preliminary results.  J Vasc 
Interv Radiol. 2009;20:1188-1192. 
16. Binkert CA, Drooz AT, Caridi JG, Sands MJ, Bjarnason H, Lynch FC, et al.  
Technical success and safety of retrieval of the G2 filter in a prospective, multicenter 
study.  J Vasc Interv Radiol. 2009;20:1449-1453. 
17 Onat L, Ganiyusufoglu AK, Mutlu A, Sirvanci M, Duran C, Ulusoy OL, et al.  
OptEase and TrapEase vena cava filters: a single-center experience in 258 patients.  
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18. Lynch FC, Kekulawela S.  Removal of the G2 filter: differences between 
implantation times greater and less than 180 days.  J Vasc Interv Radiol. 2009;20:1200-
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19. Hammond CJ, Bakshi DR, Currie RJ, Patel JV, Kinsella D, McWilliams RG, et al.  
Audit of the use of IVC filters in the UK: experience from three centres over 12 years.  
Clin Radiol. 2009;64:502-510. 
20. Kalva SP, Marentis TC, Yeddula K, Somarouthu B, Wicky S, Stecker MS.  Long-
term safety and effectiveness of the “OptEase” vena cava filter.  Cardiovasc Intervent 
Radiol. 2011;34:331-337. 
21. Shaw CM, Scorza LB, Waybill PN, Singh H, Lynch FC.  Optional vena cava filter 
use in the elderly population.  J Vasc Interv Radiol. 2011;22:824-828. 
22. Johnson MS, Nemcek AA Jr, Benenati JF, Baumann DS, Dolmatch BL, Kaufman JA, 
et al.  The safety and effectiveness of the retrievable option inferior vena cava filter: a 
United States prospective multicenter clinical study.  J Vasc Interv Radiol. 2010;21:1173-
1184. 
23. Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, et al.  A clinical 
trial of vena caval filters in the prevention of pulmonary embolism in patients with 
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24. The PREPIC study group.  Eight-year follow-up of patients with permanent vena 
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d’Embolie Pulmonaire par Interruption Cave) randomized study.  Circulation. 
2005;112:416-422. 
25. Rajasekhar A, Lottenberg L, Lottenberg R, Feezor RJ, Armen SB, Liu H, et al.  A 
pilot study on the randomization of inferior vena cava filter placement for venous 
thromboembolism prophylaxis in high-risk trauma patients.  J Trauma. 2011;71:323-329. 
26. Spaniolas K, Velmahos GC, Kwolek C, Gervasini A, De Moya M, Alam HB.  
Bedside placement of removable vena cava filters guided by intravascular ultrasound in 
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27. Cherry RA, Nichols PA, Snavely TM, David MT, Lynch FC.  Prophylactic inferior 
vena cava filters: do they make a difference in trauma patients?  J Trauma. 2008;65:544-
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28. Damascelli B, Ticha V, Patelli G, Lanocita R, Morosi C, Civelli E, et al.  Use of a 
retrievable vena cava filter with low-intensity anticoagulation for prevention of 
pulmonary embolism in patients with cancer: an observational study in 106 cases.  J Vasc 
Interv Radiol. 2011;22:1312-1319. 
29. Li W, Gorecki P, Semaan E, Briggs W, Tortolani AJ, D’Ayala M.  Concurrent 
prophylactic placement of inferior vena cava filter in gastric bypass and adjustable 
banding operations in the Bariatric Outcomes Longitudinal Database.  J Vasc Surg. 
2012;55:1690-1695. 
30. Trigilio-Black CM, Ringley CD, McBride CL, Sorensen VJ, Thompson JS, Longo 
GM, et al.  Inferior vena cava filter placement for pulmonary embolism risk reduction in 
super morbidly obese undergoing bariatric surgery.  Surg Obes Relat Dis. 2007;3:461-
464. 
31. Kardys CM, Stoner MC, Manwaring ML, Bogey WM, Parker FM, Powell S.  The use 
of intravascular ultrasound imaging to improve use of inferior vena cava filters in a high-
risk bariatric population.  J Vasc Surg. 2007;46:1248-1252. 
32. Obeid FN, Bowling WM, Fike JS, Durant JA.  Efficacy of prophylactic inferior vena 
cava filter placement in bariatric surgery.  Surg Obes Relat Dis. 2007;3:606-610. 
33. Kardys CM, Stoner MC, Manwaring ML, Barker M, MacDonald KG, Pender JR, et 
al.  Safety and efficacy of intravascular ultrasound-guided inferior vena cava filter in 
super obese bariatric patients.  Surg Obes Relat Dis. 2008;4:50-54. 
34. Halmi D, Kolesnikov E.  Preoperative placement of retrievable inferior vena cava 
filters in bariatric patients.  Surg Obes Relat Dis. 2007;3:602-605. 
35. Bass AR, Mattern CJ, Voos JE, Peterson MGE, Trost DW.  Inferior vena cava filter 
placement in orthopedic surgery.  Am J Orthop. 2010;39:435-439. 
36. Strauss EJ, Egol KA, Alaia M, Hansen D, Bashar M, Steiger D.  The use of 
retrievable inferior vena cava filters in orthopaedic patients.  J Bone Joint Surg (Br). 
2008;90:662-667. 

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37. Austin MS, Parvizi J, Grossman S, Restrepo C, Klein GR, Rothman RH.  The inferior 
vena cava filter is effective in preventing fatal pulmonary embolus after hip and knee 
arthroplasties.  J Arthroplasty. 2007;22:343-348. 
38. Dazley JM, Wain R, Vellinga RM, Cohen B, Agulnick MA.  Prophylactic inferior 
vena cava filters prevent pulmonary embolisms in high-risk patients undergoing major 
spinal surgery.  J Spinal Disord Tech. 2012;25:190-195. 
39. Leon L, Rodriguez H, Tawk RG, Ondra SL, Labropoulos N, Morasch MD.  The 
prophylactic use of inferior vena cava filters in patients undergoing high-risk spinal 
surgery.  Ann Vasc Surg. 2005;19:442-447. 
40. Ozturk C, Ganiyusufoglu K, Alanay A, Aydogan M, Onat L, Hamzaoglu A.  Efficacy 
of prophylactic placement of inferior vena cava filter in patients undergoing spinal 
surgery.  Spine. 2010;35:1893-1896. 
41. McClendon J, O’Shaughnessy BA, Smith TR, Sugrue PA, Halpin RJ, Morasch M, et 
al.  Comprehensive assessment of prophylactic preoperative inferior vena cava filters for 
major spinal reconstruction in adults.  Spine. 2012;37:1122-1129. 
42. Kidane B, Madani AM, Vogt K, Girotti M, Malthaner RA, Perry NG.  The use of 
prophylactic inferior vena cava filters in trauma patients: a systematic review.  Injury. 
2012;43:542-547. 
43. Stein PD, Matta F, Keyes DC, Willyerd GL.  Impact of vena cava filters on in-
hospital case fatality rate from pulmonary embolism.  Am J Med. 2012;125:478-484. 
44. O’Keefe T, Thekkumel JJ, Friese S, Shafi S, Josephs SC.  A policy of dedicated 
follow-up improves the rate of removal of retrievable inferior vena cava filters in trauma 
patients.  Am Surg. 2011;77:103-108. 
45. Mission JF, Kerlan RK, Tan JH, Fang MC.  Rates and predictors of plans for inferior 
vena cava filter retrieval in hospitalized patients.  J Gen Intern Med. 2010;25:321-325. 
46. Minocha J, Idakoji I, Riaz A, Karp J, Gupta R, Chrisman HB, et al. Improving 
inferior vena cava filter retrieval rates: impact of a dedicated inferior vena cava filter 
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47. Ko SH, Reynolds BR, Nicholas DH, Zenati M, Alarcon L, Dillavou ED, et al. 
Institutional protocol improves retrievable inferior vena cava filter recovery rate. Surgery. 
2009;146:809-816. 
48. Canos D.  Sample size requirements.  Presented at: IVC Filter Meeting - 
SIR/SVS/IVC Filter Manufacturers/Food and Drug Administration. August 10, 2012; 
Silver Spring, MD. 
49. Johnson M.  The PRESERVE Study:  PREdicting the Safety and Effectiveness of 
InferioR VEna Cava Filters.  Paper presented at: VIVA. October 10, 2012; Las Vegas, 
NV. 
 
50. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, et al.  Design and 
analysis of randomized clinical trials requiring prolonged observation of each patient.  II. 
analysis and examples.  Br J Cancer. 1977;35:1-39. 
51. Schafer JL. Analysis of Incomplete Multivariate Data, London: Chapman & Hall; 
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52. Schafer J.L. Missing Data: A Review. A seminar sponsored by the Cleveland Chapter 
of the American Statistical Association. Cleveland, Ohio. October 14, 2002. 
 
 

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APPENDIX A 
Contact Information 
 
Global Sponsor and Monitor 
Cook Research Incorporated 
1 Geddes Way 
West Lafayette, IN  47906 
USA 
 
Contacts: 
Jennifer L. Kerr 
 
President, Cook Research Incorporated 
Telephone: 
765.463.7537 
Fax: 
765.497.0641 
Email: 
Jennifer.Kerr@CookMedical.com  
 
 
 
Manufacturer 
William Cook Europe ApS 
Sandet 6, 4632 Bjaeverskov 
Denmark 
 
Contact:  
Henriette Christiansen, Director of Regulatory Affairs 
Telephone:  
+45 5686 8686 
Fax:  
+45 5686 8696 
Email:  
Henriette.Christiansen@CookMedical.com 
 
 
 

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APPENDIX B 
Written Procedures for Monitoring Studies 
 
A. Selection of the monitor. 
Designated by the sponsor to oversee the clinical study, the monitor may be an employee 
of Cook, an employee of a monitoring organization (CRO), or an independent contractor 
or consultant. The monitor shall be qualified by training and experience to monitor the 
study in accordance with all applicable regulations and standards for conducting clinical 
studies. 
B. General duties of the monitor. 
The monitor must ensure that the study is conducted in accordance with: 
1. The signed investigator agreement. 
2. The Clinical Investigation Plan (CIP). 
3. Any conditions imposed by the IRB/EC/REB or regulatory authority. 
4. The requirements of the applicable regulations and standards. 
C. Reports by the monitor to the sponsor. 
1. Any noncompliance with the items listed above. In the event that the investigator 
is not complying with the requirements outlined above, it is the sponsor's 
responsibility to secure compliance. 
2. Any adverse events or effects that are potentially reportable to a regulatory 
authority. 
 
D. Initiating the study. 
 
Prior to initiating any clinical use of the device, the monitor/sponsor representative will 
participate in a pre-study or initiation visit with each clinical site.  
 
 
 

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At a minimum, the following items shall be addressed during the site initiation visit: 
 
1. Provide training to investigator on his/her responsibilities per the investigator 
agreement, applicable laws, regulations and standards; and 
2. Provide training to investigator that the IRB/EC/REB approval letter and 
informed consent/patient information should be on file before initiation of the 
clinical study. 
Additionally, training may be provided to the investigator on: 
1. The regulatory status of the device and the requirements for the accountability of 
same;  
2. The nature of the CIP; 
3. The requirements for an adequate and well-controlled clinical study; 
4. His or her obligation to obtain informed consent in accordance with applicable 
regulations; 
5. His or her obligation to ensure continuing review of the clinical study by the 
IRB/EC/REB in accordance with conditions of approval and applicable 
regulations and to keep the sponsor informed of such IRB/EC/REB approval and 
subsequent IRB/EC/REB actions concerning the study; 
6. The importance of access to an adequate number of suitable patients to conduct 
the study; 
7. The importance of adequate facilities for conducting the clinical study; and 
8. The importance of sufficient time from other obligations to carry out the 
responsibilities to which the investigator is committed by applicable regulations. 
 
E. During the course of the study, at the direction of the project manager, the monitor 
should visit the site frequently enough to ensure that: 
1. The facilities and research staff used by the investigator continue to be 
acceptable for purposes of the clinical study; 
2. The applicable version of the CIP and agreements are being followed; 
3. Changes to the CIP, informed consent/patient information have been approved 
by the IRB/EC/REB and/or reported to the sponsor and the IRB/EC/REB; 
4. Accurate, complete, and current records are being maintained; 
5. Accurate, complete, and timely reports are being made to the sponsor and 
IRB/EC/REB; and 

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COMPANY CONFIDENTIAL 
CIP 12-018-10, Version Date 01 March 2018 
6. The investigator is carrying out the agreed-upon activities and has not delegated 
them to other previously unspecified staff. 
 
As appropriate, the following tasks could be performed during periodic visits:  
1. Device accountability review; 
2. Adverse event review to ensure that events are appropriately reported within the 
time periods required by the sponsor, CIP, IRB/EC/REB, and applicable 
regulatory requirements; and 
3. Source data verification per the monitoring plan to determine that: 
a. Informed consent/patient information has been documented in accordance 
with applicable regulations and expectations of the local IRB/EC/REB; 
b. The information recorded in the CRFs (paper or electronic) is complete, 
accurate, and legible; 
c. There are no omissions in the CRFs of specific data elements, such as the 
administration to any patient of concomitant test articles or the development 
of an intercurrent illness; 
d. Missing visits or examinations are noted; and 
e. Patients failing to complete the clinical study and the reason for each failure 
are noted. 
F. Records of the monitor. 
The monitor shall prepare and maintain records of each initiation visit and each periodic 
visit, general site contact, or discussion. These will include: 
1. Date, name, and address of the investigator, and names of other staff members 
present at each meeting. 
2. A summary of the findings of the visit. 
3. A statement of any action taken by the monitor or investigator to correct any 
deficiencies noted. 
4. The monitor shall immediately notify the sponsor of any conditions of 
noncompliance with the CIP, conditions of IRB/EC/REB or regulatory authority 
approval, or the applicable regulations. 
 

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COMPANY CONFIDENTIAL 
CIP 12-018-10, Version Date 01 March 2018 
 
APPENDIX C 
Definitions 
 
Access site complications with clinical sequelae - Arteriovenous fistula, hematoma, or 
bleeding requiring transfusion (≥ 2 units), hospitalization (either admission or extended 
stay), or further treatment. 
 
Access site thrombus – Occlusive or nonocclusive thrombus developing at venotomy 
site after filter insertion or retrieval, documented by ultrasound or other imaging. 
 
Adverse events – Definition may be found in applicable regulations. 
 
Adverse device effects – Definition may be found in applicable regulations. 
 
Clinical fracture – A loss of structural integrity (breakage or separation) of the filter 
identified by imaging and associated with clinical sequelae and/or requiring intervention. 
 
Clinical migration – Caudal or cranial movement of a filter resulting in surgical or 
endovascular intervention. 
 
Clinical perforation – Protrusion of filter legs through the wall of the IVC causing 
hemorrhage or hematoma or touching, impressing, or perforating another organ (e.g., 
liver, bowel, aorta, psoas muscle, vertebral body, lymph nodes).  Acute perforation 
occurring during placement of the filter is considered a placement problem.  Documented 
using CT. 
 
Deep vein thrombosis (DVT) – Thrombus in the deep veins, usually of the lower 
extremities or pelvis.  Documented by contrast venography, duplex ultrasound, CT, or 
magnetic resonance (MR) venography. The proximal extent of thrombus should be 
identified. 
 
Device deficiencies – Definition may be found in applicable regulations. 
 

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COMPANY CONFIDENTIAL 
CIP 12-018-10, Version Date 01 March 2018 
Filter deformation – Insufficient opening of filter (i.e., filter legs do not adjust 
themselves to the size of the IVC), collapse of filter, uneven distribution of filter legs, 
bending of filter, or crossing or entangling of two or more filter legs. 
 
Filter embolization – Post-placement movement of the filter or its components to a 
distant anatomic site completely out of the target zone (i.e., heart/lungs). Documented by 
imaging or autopsy. 
 
Filter fracture – Any loss of structural integrity (breakage or separation) of the filter 
identified by imaging or autopsy.  Documented by imaging or at autopsy. 
 
Filter leg interaction with the IVC1 –  
Grade 0: 
Normal; filter strut confined entirely within the IVC. 
Grade 1: 
Filter strut is immediately adjacent to the external aspect of the IVC wall 
(likely reflecting tenting of the IVC wall). 
Grade 2: 
Filter strut is entirely outside of the IVC lumen and within the 
retroperitoneum as evidenced by a “halo” of retroperitoneal fat around 
axially viewed strut. 
Grade 3: 
Filter strut is touching, impressing, or perforating another organ (e.g., 
liver, bowel, aorta, psoas muscle, vertebral body, lymph nodes).  
 
Filter migration – Change in filter position compared to its deployed position (cranial or 
caudal).  Migration will be classified as significant (i.e., > 20 mm) or insignificant  
(i.e., < 20 mm).  Documented by plain radiograph, CT, or venography. 
 
Filter tilt –  Angle of the longitudinal axis of the filter with respect to the longitudinal 
IVC axis.  Tilt will be classified as significant (i.e., ≥ 16° relative to the IVC longitudinal 
axis) or insignificant (i.e., < 16° relative to the IVC longitudinal axis).  A filter is 
considered free of tilt if it appears centered in the IVC.  Documented by plain radiograph 
or venography. 
 
                                                 
 
1 Oh JC, Trerotola SO, Dagli M, Shlansky-Goldberg RD, Soulen MC, Itkin M, et al. Removal of retrievable 
inferior vena cava filters with computed tomography findings indicating tenting or penetration of the 
inferior vena cava wall.  J Vasc Interv Radiol. 2011;22:70-74. 

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COMPANY CONFIDENTIAL 
CIP 12-018-10, Version Date 01 March 2018 
IVC thrombotic occlusion – Presence of an occluding thrombus in the IVC occurring 
after filter placement.  Documented by ultrasound, CT, MR, venography, or autopsy.  
Methods of diagnosis should be noted, along with extent of thrombus.  May be 
symptomatic or asymptomatic. 
 
Major adverse events – Events of clinical perforation, clinical migration, clinical 
fracture, embolization of the filter or filter fragments to the heart or lungs, IVC 
thrombotic occlusion, new symptomatic DVT while a filter is indwelling, access site 
complications with clinical sequelae, and procedure-/device-related death. 
 
Premature release of filter – The filter is released from the deployment system before 
the physician intended. 
 
Procedure-/device-related death – Death directly attributable to the filter or filter 
placement or retrieval procedure itself, documented by clinical findings, imaging, or 
autopsy, or as adjudicated by a Clinical Events Committee. 
 
Pulmonary embolism (PE) – Emboli to lungs via the pulmonary artery, which can arise 
from deep venous thrombosis in the lower extremities or pelvis.  Documented using 
pulmonary arteriography, cross-sectional imaging, or significant change in 
ventilation/perfusion lung scan, or at autopsy.  PE will be categorized by type.2 
 
Pulmonary embolism (PE), massive – Acute PE with sustained hypotension (systolic 
blood pressure < 90 mmHg for at least 15 minutes or requiring inotropic support, not due 
to a cause other than PE, such as arrhythmia, hypovolemia, sepsis, or left ventricular 
[LV] dysfunction), pulselessness, or persistent profound bradycardia (heart rate <  
40 bpm with signs or symptoms of shock). 
 
                                                 
 
2 Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al. Management of 
massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic 
thromboembolic pulmonary hypertension: A scientific statement from the American Heart Association. 
Circulation. 2011;123:1788-1830. 

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COMPANY CONFIDENTIAL 
CIP 12-018-10, Version Date 01 March 2018 
Pulmonary embolism (PE), submassive – Acute PE without systemic hypotension 
(systolic blood pressure ≥ 90 mmHg) but with either right ventricular (RV) dysfunction 
or myocardial necrosis, where: 
 
RV dysfunction is defined as the presence of at least 1 of the following: 
- 
RV dilation (apical 4-chamber RV diameter divided by LV diameter > 
0.9) or RV systolic dysfunction on echocardiography; 
- 
RV dilation (4-chamber RV diameter divided by LV diameter > 0.9) on 
CT; 
- 
Elevation of BNP (> 90 pg/mL); 
- 
Elevation of N-terminal pro-BNP (> 500 pg/mL); or 
- 
Electrocardiographic changes (new complete or incomplete right bundle-
branch block, anteroseptal ST elevation or depression, or anteroseptal T-
wave inversion). 
 
Myocardial necrosis is defined as either of the following: 
- 
Elevation of troponin I (> 0.4 ng/mL) or 
- 
Elevation of troponin T (> 0.1 ng/mL). 
 
Pulmonary embolism (PE), low-risk – Acute PE and the absence of the clinical markers 
of adverse prognosis that define massive or submassive PE. 
 
Serious adverse events – Definition may be found in applicable regulations. 
 
Serious adverse device effects – Definition may be found in applicable regulations. 
 
Significant trapped thrombus in filter – Thrombus filling > 25% of the filter. 
 
Technical placement success – Deployment of filter in a location suitable to provide 
sufficient mechanical protection against PE with no filter deformation, fracture, 
premature release, or clinical migration. 
 
Technical retrieval success – Endovascular retrieval of complete filter. 
 
Unanticipated serious adverse device effects – Definition may be found in applicable 
regulations.