Multi-center, Single Arm Continued Access Protocol to Evaluate the Mid-Bore Venous VCS for the Management of the Femoral Venotomy After Catheter-based Interventions Via 6-12F Procedural Sheaths With Single or Multiple Access Sites Per Limb
Phase: NA
Conditions: Surgical Wound
Sponsor: Cardiva Medical, Inc.

 
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Clinical Investigation Plan (CIP) and Protocol 
“AMBULATE CAP STUDY” 
CONTINUED ACCESS PROTOCOL (CAP) 
 
MULTI-CENTER, SINGLE ARM CONTINUED ACCESS PROTOCOL TO EVALUATE THE CARDIVA MID-BORE VENOUS 
VASCULAR CLOSURE SYSTEM (VVCS) FOR THE MANAGEMENT OF THE FEMORAL VENOTOMY AFTER CATHETER-
BASED INTERVENTIONS PERFORMED VIA 6- 12 FR PROCEDURAL SHEATHS WITH SINGLE OR MULTIPLE ACCESS SITES 
PER LIMB  
 
 
The trial will be performed in accordance with the relevant parts of Title 21 CFR Parts 812, 50, 54, and 
56; and the ICH Guidelines for Good Clinical Practices (E6). 
Sponsor: 
CARDIVA Medical, Inc. 
2900 Lakeside Drive, Suite 160 
Santa Clara, CA  95054 
Study Responsibility: 
CARDIVA Medical, Inc. 
2900 Lakeside Drive, Suite 160 
Santa Clara, CA  95054 
Principal Investigator: 
Amin M. Al-Ahmad M.D. FACC, FHRS, CCDS 
Texas Cardiac Arrhythmia 
Austin, Texas, USA 
Protocol Number: 
PTL 0543 
IDE: 
G170144 
Study Centers: 
See the study manual for a list of study centers 
Version: 
Version 02  
This protocol contains confidential information for use by the Investigators and their designated 
representatives participating in this clinical investigation. It should be held confidential and maintained 
in a secure location. 
Do not copy or distribute without written permission. 

 
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Protocol Synopsis 
“AMBULATE CAP STUDY” CONTINUED ACCESS PROTOCOL (CAP) 
MULTI-CENTER, SINGLE ARM CONTINUING ACCESS PROTOCOL TO EVALUATE THE CARDIVA MID-BORE VENOUS 
VASCULAR CLOSURE SYSTEM (VVCS) FOR THE MANAGEMENT OF THE FEMORAL VENOTOMY AFTER CATHETER-
BASED INTERVENTIONS PERFORMED VIA 6- 12 FR PROCEDURAL SHEATHS WITH SINGLE OR MULTIPLE ACCESS 
SITES PER LIMB 
Primary 
Objective 
The objective of the trial is to demonstrate the safety and effectiveness of the Cardiva 
Mid-Bore Venous Vascular Closure System (VVCS) in sealing femoral venous access sites 
at the completion of catheter-based procedures performed through 6-12 Fr introducer 
sheaths, while allowing for one or more of the following: elimination of the urinary 
catheter, elimination of protamine, or allowing same (calendar) day discharge for the 
appropriate patient population.  
 Test Device 
Cardiva Mid-Bore Venous Vascular Closure System (VVCS) – 6-12 Fr device with 23 Fr Disc 
(~8 mm) 
Indication 
for Use 
The Cardiva Mid-Bore Venous Vascular Closure System (VVCS) is indicated for the 
percutaneous closure of femoral venous access sites while reducing times to ambulation 
,and discharge eligibility in patients who have undergone catheter-based procedures 
utilizing 6 – 12 Fr procedural sheaths, ranging from a single access site in one limb to 
multiple access sites in both limbs. 
Study 
Questions 
The Cardiva Mid-Bore VVCS meets its intended use while allowing for one or more of the 
following:  
• 
Elimination of the urinary catheter  
• 
Elimination of protamine without compromising ambulation time, and / or  
• 
Allowing same calendar day discharge for the appropriate patient population 
without impacting the safety profile of the device  
Study Design 
A prospective multi-center single-arm clinical continued access protocol, designed to 
evaluate the safety and effectiveness of the study device in sealing multiple femoral 
venous access sites at the completion of catheter-based procedures performed through 6 
- 12 Fr introducer sheaths, while allowing for one or more of the following: elimination of 
the urinary catheter, elimination of protamine and / or allowing same calendar day 
discharge for the appropriate patient population. 
Number of 
Patients 
Planned enrollment is approximately 300 individual subjects. Each subject can be co-
enrolled in multiple study groups of the study and will contribute data to the study 
group(s) in which they are enrolled.  
 A subject may not be enrolled in the No Protamine and Same Calendar Day Discharge 
arms simultaneously. 
Number of 
Sites 
Up to 5 sites U.S., with a minimum of 2 sites enrolling subjects in the trial. Any one site 
will not enroll more than 60% of the subjects. The sites will be sites that participated in 
the AMBULATE Study [G170144]. 

 
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Duration of 
Trial 
Each enrolled subject will have follow-up contact at 30 days +/- 10 days post-procedure 
that will be either an office visit or a phone call. Once all subjects have completed this 
follow-up, the study will be considered complete.  
Primary 
Effectiveness 
Endpoint 
Overall Procedure Success (pooled across all study groups)  
Final hemostasis at all venous access sites and freedom from major venous access site 
closure-related complications through 30 day follow-up. (Per-patient analysis pooled 
across all study groups) 
Secondary 
Effectiveness 
Endpoints 
• 
Study Group Success Rate (defined for each study arm):  
o No Urinary Catheter group: No peri-procedural urinary catheter insertion 
required through successful Ambulation. (Per-patient analysis) 
o No Protamine group: No delay in Ambulation due to access site bleeding 
in subjects who receive heparin but are not reversed with protamine 
(Per-patient analysis)   
o Same Calendar Day  Discharge group: Discharge within the same calendar 
day from the start of the procedure without the need for re-
hospitalization within 72 hours of hospital discharge due to access site 
complications. (Per-patient analysis)   
• 
Device Success, defined as the ability to deploy the delivery system, deliver the 
collagen, and achieve hemostasis with the Mid-Bore VVCS.  
(Per-access site analysis)  
Primary Safety 
Endpoint 
On a per-limb basis, the rate of combined major venous access site closure-related 
complications through 30 days post-procedure +/- 10 days, attributed directly to the 
closure method (i.e., “device-related” with no other likely attributable cause): 
• Access site-related bleeding requiring transfusion; 
• Vascular injury requiring surgical repair;  
• Access site-related infection confirmed by culture and sensitivity, requiring 
intravenous antibiotics and/or extended hospitalization; 
• New onset permanent access site-related nerve injury (i.e., persisting for > 30 
days);  
• New onset access site-related nerve injury in the ipsilateral lower extremity 
requiring surgical repair; 
• Pulmonary embolism requiring surgical or endovascular intervention and/or 
resulting in death, to be confirmed by CT pulmonary angiography, lung 
ventilation/perfusion scan (VQ scan) or autopsy;  
• Pulmonary embolism NOT requiring surgical or endovascular intervention 
and/or NOT resulting in death, to be confirmed by CT pulmonary angiography 
or lung ventilation/perfusion scan (VQ scan). 

 
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Secondary 
Safety 
Endpoint 
On a per-limb basis, the rate of combined minor venous access site closure-related 
complications through 30 days post-procedure +/- 10 days, attributed directly to the 
closure method (i.e., “device-related” with no other likely attributable cause): 
• 
Access site-related bleeding requiring greater than 30 minutes of 
continual manual compression to achieve initial venous 
hemostasis; 
• 
Access site-related hematoma > 6 cm documented by ultrasound; 
• 
Late access site-related bleeding (following hospital discharge); 
• 
Ipsilateral deep vein thrombosis confirmed by 
ultrasound/imaging; 
• 
Localized access site infection confirmed by culture and 
sensitivity, treated with intramuscular or oral antibiotics; 
• 
Arteriovenous fistula requiring treatment;  
• 
Arteriovenous fistula not requiring treatment; 
• 
Pseudoaneurysm requiring thrombin injection, fibrin adhesive 
injection or ultrasound-guided compression; 
• 
Pseudoaneurysm not requiring treatment. 
• 
Access site-related vessel laceration; 
• 
Access site-related wound dehiscence; 
• 
Transient access site-related nerve injury. 
 

 
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Pre-Operative 
Inclusion 
Criteria 
All subjects are required to meet the following inclusion criteria in order to be considered 
eligible for participation in this trial: 
1. ≥18 years of age; 
2. Capable and willing to give informed consent; 
3. Acceptable candidate for an elective, non-emergent catheter-based procedure via the 
common femoral vein(s) using a 6 to 12 Fr inner diameter introducer sheath  
4. Able and willing to complete a 30 (± 10) days post-procedure follow-up contact; 
5. Acceptable candidate for emergent vascular surgery, and/or manual compression of 
the venous access site; 
6. Study Group Criteria: The subject is eligible for at least one of the following study 
groups: 
a. Same Calendar Day  Discharge Candidate: 
• 
The subject is expected to undergo an Atrial Fibrillation, Supraventricular 
Tachycardia, Ventricular Tachycardia or Atrial Flutter procedure.    
• 
If procedural heparin is planned to be used, it must be reversed at or before 
venous closure.  
• 
Physician or designee is expected to be on site for discharge evaluation. 
• 
Supraventricular Tachycardia (SVT) or Atrial Flutter Subjects: No Additional 
Criteria  
• 
Atrial Fibrillation or Ventricular Tachycardia Procedure Subjects: CHADS2 Score 
must be ≤1: 
CHADS 2 Score: Stroke Risk Assessment in Atrial Fibrillation 
Score 
CHADS2 Risk Criteria 
1 point 
C: Congestive heart failure 
1 point 
H: Hypertension 
1 point 
A: Age ≥ 75 years 
1 point 
D: Diabetes mellitus 
2 points 
S2: Previous Stroke / transient ischemic 
attack / thromboembolism 
b. No Urinary Catheter Candidate:  
• 
The subject is a candidate to undergo the procedure and bedrest without a 
urinary catheter (i.e., indwelling, condom or straight catheter insertion). 
• 
No history of urinary retention due to e.g. anesthesia, prostate issues, etc. 
c. No Protamine Candidate: The subject is a candidate to receive procedural heparin 
for anti-coagulation management. 
Note: 
Initial subject eligibility will be determined based on pre-operative screening.  
Final subject enrollment in one or more study groups will be determined at the end the 
procedure based on general intra-op exclusion criteria, as well as group-specific criteria.  
Enrollment is thus determined intra-operatively, at the end of the case.  

 
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Pre-Operative 
Exclusion Criteria 
Subjects will be excluded from participating in this study if they meet any of the 
following criteria prior to initiation of the index procedure: 
1.  Advanced refusal of blood transfusion, if it should become necessary; 
2. Active systemic infection, or cutaneous infection or inflammation in the 
vicinity of the groin; 
3. Pre-existing immunodeficiency disorder and/or chronic use of high dose 
systemic steroids; 
4. Known history of bleeding diathesis, coagulopathy, hypercoagulability, or 
current platelet count < 100,000 cells/mm3; 
5. Severe co-existing morbidities, with a life expectancy of less than 12 months; 
6. Currently involved in any other investigational clinical trial that may interfere 
with the outcomes of this study in the opinion of investigator; 
7. Femoral arteriotomy in either limb with any of the following conditions: 
a. access within < 10 days 
b. any residual hematoma, significant bruising, or known associated vascular 
complications 
c. use of a vascular closure device within the previous 30 days; 
8. Femoral venotomy in either limb with any of the following conditions: 
a. access within < 10 days 
b. any residual hematoma, significant bruising, or known associated vascular 
complications 
c use of a vascular closure device  
9. Any planned procedure involving femoral arterial or venous access in either 
limb within the next 30 days; 
10. Any history of deep vein thrombosis, pulmonary embolism or 
thrombophlebitis;  
11. Significant anemia with a hemoglobin level less than 10 g/dL or a hematocrit 
less than 30%; 
12. Females who are pregnant, planning to become pregnant within 3 months of 
the procedure, or who are lactating; 
13. Extreme morbid obesity (BMI greater than 45 kg/m2) or underweight (BMI 
less than 20 kg/m2); 
14. Unable to routinely walk at least 20 feet without assistance; 
15. Known allergy/adverse reaction to bovine derivatives; 
16. Administration of low molecular weight heparin (LMWH) within 8 hours 
before or after the procedure; 
17. Planned procedures or concomitant condition(s) that may extend ambulation 
attempts beyond 2-3 hours, and/or hospitalization time (e.g., staged 
procedure, serious co-morbidity), in the opinion of the Investigator. 

 
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Intra-Operative 
Exclusion Criteria 
Subjects will be excluded from participating in this study if any of the following 
exclusion criteria occur during the index procedure: 
 
General Intra-op Exclusion Criteria: 
1. Any attempt at femoral arterial access during the procedure; 
2. Any procedural complications that may extend routine recovery, ambulation 
and discharge times; 
3. If the physician deems that a different method should be used to achieve 
hemostasis of the venous access sites, or that the subject should not attempt 
ambulation according to the protocol requirements; 
4. All venous access sites must comply with the following exclusion criteria, 
assessed immediately prior to enrollment: 
a. Difficult insertion of procedural sheath or needle stick problems at the 
onset of the procedure (e.g., multiple stick attempts, accidental arterial 
stick with hematoma, “back wall stick”, etc.) in any of the study veins; 
b. A procedural sheath < 6 Fr or > 12 Fr in inner diameter is present at time 
of closure; 
c. A procedural sheath > 12 Fr inner diameter at any time during the 
procedure. 
d. Venous access site location is noted to be “high”, above the inguinal 
ligament (cephalad to lower half of the femoral head or the inferior 
epigastric vein origin from the external iliac vein); 
e.  Intra-procedural bleeding around sheath, or suspected intraluminal 
thrombus, hematoma, pseudoaneurysm, or AV fistula; 
f.   Length of the tissue tract, the distance between the anterior venous wall 
and skin, is estimated to be less than 2.5 cm. 
 

 
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Additional Intra-
Operative 
Screening: Inclusion 
Criteria  
 
Study Group Criteria: The subject must be eligible for at least one of the following 
study groups:  
 
a) Same Calendar Day  Discharge (all criteria apply): 
• 
In the Investigator’s opinion, the subject is a candidate for Same Calendar 
Day Discharge per protocol.  
• 
If procedural heparin is used, it was/will be reversed at or before venous 
closure.  
• 
Physician or designee must be on site for discharge evaluation. 
• 
Supraventricular Tachycardia (SVT) or Atrial Flutter Subjects: No 
Additional Criteria  
• 
Atrial Fibrillation or Ventricular Tachycardia Procedure Subjects: 
CHADS2 Score is ≤1, as assessed pre-operatively. 
• 
The subject is not enrolled in the No Protamine Group. 
CHADS 2 Score: Stroke Risk Assessment in Atrial Fibrillation 
Score 
CHADS2 Risk Criteria 
1 point 
Congestive heart failure 
1 point 
Hypertension 
1 point 
Age ≥ 75 years 
1 point 
Diabetes mellitus 
2 points 
Stroke / transient ischemic attack / 
thromboembolism 
 
b) No Urinary Catheter:  
• 
The subject does not have a urinary catheter inserted/indwelling at the 
end of the procedure, just prior to enrollment 
 
c) No Protamine:  
• 
The subject received procedural heparin for anti-coagulation management 
and did not/will not receive protamine. 
• 
The subject is not enrolled in the Same Calendar Day Discharge Group. 
*a subject may not be co-enrolled in Same Calendar Day Discharge and No 
Protamine study groups.  
Study Administration 
Clinical Research 
Organization (CRO) 
Chellew Clinical Outsourcing, LLC (CCO) 
7844 E. Riverdale St., Mesa, AZ 85207 
 
 
 

 
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Table of Contents 
Protocol Synopsis ..................................................................................................................................... 3 
Table of Contents ................................................................................................................................... 10 
1. 
Introduction ................................................................................................................................... 13 
1.1. 
Background ............................................................................................................................. 13 
1.2. 
Unmet Clinical Need ............................................................................................................... 15 
1.3. 
AMBULATE, A Clinical Investigation for Venous Closure [PTL 0508] ...................................... 15 
1.4. 
The AMBULATE Continued Access Protocol (CAP) ................................................................. 17 
1.5. 
Real World Experience: VASCADE Arterial VCS Real World Experience for Venous Closure . 18 
1.6. 
Design Verification Testing ..................................................................................................... 19 
 
Design verification testing including the following: ......................................................... 19 
1.7. 
Pre-clinical Testing .................................................................................................................. 19 
 
Pre-clinical Chronic GLP Study Overview [RPT 0503] ....................................................... 19 
 
Pre-clinical Acute Study Overview [RPT 0533] ................................................................. 20 
1.8. 
Clinical Studies ........................................................................................................................ 20 
 
AMBULATE Study Mid-Bore VVCS Sub-study analysis for CE Mark [RPT 0527] ............... 20 
 
RESPECT Trial using VASCADE arterial VCS ....................................................................... 24 
1.9. 
Risks and Benefits ................................................................................................................... 28 
 
Risks .................................................................................................................................. 28 
 
Benefits ............................................................................................................................. 28 
2. 
Device Description ......................................................................................................................... 29 
Device Labeling .................................................................................................................................. 30 
3. 
AMBULATE CAP Study Objective ................................................................................................... 30 
4. 
Study Design .................................................................................................................................. 30 
4.1. 
Overview ................................................................................................................................. 30 
4.2. 
Sample Size ............................................................................................................................. 30 
5. 
Study Population ............................................................................................................................ 31 
5.1. 
Selection Criteria .................................................................................................................... 31 
 
Pre-Operative Inclusion Criteria ....................................................................................... 32 
 
Pre-Operative Exclusion Criteria ...................................................................................... 33 
 
Intra-Operative Inclusion Criteria ..................................................................................... 34 
 
Intra-Operative Inclusion Criteria ..................................................................................... 35 
5.2. 
Withdrawal of Subjects .......................................................................................................... 35 
6. 
Written Informed Consent ............................................................................................................. 36 
7. 
Study Procedures and Enrollment ................................................................................................. 36 
7.1. 
Duration of Subject Participation ........................................................................................... 36 
7.2. 
Enrollment .............................................................................................................................. 36 
7.3. 
Visit Schedule ......................................................................................................................... 37 
7.4. 
Study Procedures .................................................................................................................... 38 
 
Pre-Operative ................................................................................................................... 38 
 
Intra-Operative – Data Collection for All Subjects ........................................................... 38 
 
Intra-Operative – Access Site Requirements .................................................................... 38 
 
Intra-Operative - Subject Identification ........................................................................... 38 

 
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Access Site Closure Instructions ....................................................................................... 39 
 
Post-Operative.................................................................................................................. 40 
7.5. 
Follow-up at 30 (+/- 10) Days ................................................................................................. 42 
7.6. 
Study Exit ................................................................................................................................ 42 
8. 
Assessment of Effectiveness and Safety ........................................................................................ 42 
8.1. 
Primary Effectiveness Endpoint .............................................................................................. 42 
8.2. 
Secondary Effectiveness Endpoints ........................................................................................ 43 
8.3. 
Primary Safety Endpoint ......................................................................................................... 43 
8.4. 
Secondary Safety Endpoint ..................................................................................................... 43 
9. 
Statistical Considerations ............................................................................................................... 44 
9.1. 
Analysis Populations and Data Handling Conventions ........................................................... 44 
 
Effectiveness ..................................................................................................................... 44 
 
Safety ................................................................................................................................ 44 
 
Missing Data ..................................................................................................................... 44 
9.2. 
Statistical Analysis Plan ........................................................................................................... 44 
 
Baseline Subject Characteristics ....................................................................................... 44 
 
Effectiveness ..................................................................................................................... 44 
 
Safety ................................................................................................................................ 45 
9.3. 
Sample Size Justification ......................................................................................................... 45 
10. Data Management – Data Collection and Processing .................................................................... 45 
11. Monitoring Procedures .................................................................................................................. 46 
11.1. Monitoring .............................................................................................................................. 46 
11.2. Investigational Device Distribution and Accountability ......................................................... 47 
 Investigational Device Distribution .................................................................................. 47 
 Device Accountability ....................................................................................................... 47 
 Return of Materials Upon Study Termination .................................................................. 47 
12. Quality Control and Quality Assurance .......................................................................................... 48 
12.1. Site Training ............................................................................................................................ 48 
12.2. Investigator and Co-Investigator Training .............................................................................. 48 
12.3. Audits and Inspections ........................................................................................................... 49 
13. Adverse Events ............................................................................................................................... 49 
General ............................................................................................................................................... 49 
13.1. Reporting of Serious and Non-Serious Adverse Events .......................................................... 51 
 General Reporting Requirements (Serious & Non-Serious Adverse Events) ................... 51 
13.2. Device Failures and Malfunctions .......................................................................................... 52 
14. Study Committee ........................................................................................................................... 52 
14.1. Data Safety Monitoring .......................................................................................................... 52 
15. Ethical Considerations .................................................................................................................... 52 
15.1. Trial Conduct & the Declaration of Helsinki ........................................................................... 52 
15.2. Institutional Review Board/Ethics Committee ....................................................................... 52 
15.3. Informed Consent Form ......................................................................................................... 53 
15.4. Amending the Protocol ........................................................................................................... 53 
15.5. Emergency Actions ................................................................................................................. 54 

 
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15.6. Protocol Deviations ................................................................................................................ 54 
15.7. Coverage of Expenses ............................................................................................................. 55 
15.8. Confidentiality ........................................................................................................................ 55 
16. Study Administration ..................................................................................................................... 55 
16.1. Pre-Study Documentation Requirements .............................................................................. 55 
16.2. Source Documentation ........................................................................................................... 56 
16.3. Record Retention & Custody .................................................................................................. 56 
16.4. Criteria for Terminating Study ................................................................................................ 57 
16.5. Criteria for Suspending/Terminating a Study Center ............................................................. 57 
16.6. Investigator Responsibilities ................................................................................................... 57 
17. Publication Policy ........................................................................................................................... 58 
18. Regulatory Considerations ............................................................................................................. 58 
18.1. Role of Cardiva Medical .......................................................................................................... 58 
18.2. General Duties [21 CFR 812. 40] ............................................................................................. 59 
18.3. Monitoring [21 CFR 812. 46] .................................................................................................. 59 
18.4. Supplemental Applications [21 CFR 812. 335 (A) and (B)] ..................................................... 59 
18.5. Maintaining Records [21 CFR 812. 140 (B)] ............................................................................ 59 
18.6. Submitting Reports [21 CFR 812. 150 (B)] .............................................................................. 59 
18.7. Site Record Retention Policy [21 CFR 812. 140 (D)] ............................................................... 60 
18.8. Informed Consent & Institutional Review Board (IRB) [21 CFR Parts 50 & 56] ...................... 60 
19. Abbreviations and Definitions ....................................................................................................... 61 
19.1. Abbreviations.......................................................................................................................... 61 
19.2. Definitions .............................................................................................................................. 62 
19.3. Bibliography ............................................................................................................................ 67 
20. Attachment 1: Investigator Responsibilities, Records and Reports ............................................... 68 
20.1. Investigator Responsibilities ................................................................................................... 68 
20.2. Investigator Records ............................................................................................................... 68 
20.3. Investigator Reports ............................................................................................................... 68 
21. Attachment 2: Sample Informed Consent Form ............................................................................ 70 
22. Attachment 3: Instructions For Use (IFU) ...................................................................................... 71 
23. Attachment 4: Patient Experience Survey ..................................................................................... 72 
 
 
 

 
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1. Introduction  
1.1. Background  
While a variety of closure device options exist for femoral arterial closure, there are few closure 
device options for venous closure.  Procedures requiring venous access such as venous stenting 
(single access site), cardiac ablation (multi-access site), DVT treatments (single access site), etc., are 
growing. Cardiva asserts that there is a need for developing percutaneous closure of venous access 
in patients.  
Characteristics in the venous environment, such as lower blood velocity and pressure compared to 
arteries, can contribute to patient complications such as DVT due to reduced blood flow directly, 
e.g., manual compression, and indirectly e.g., prolonged bedrest.  Vascular closure devices with 
intraluminal components could contribute to reduction in blood flow and/or increased risk of 
thrombosis.   
The Cardiva Mid-Bore VVCS has no intraluminal components. It is based on the previously approved 
VASCADE® VCS arterial platform [P120016]1 indicated for percutaneous closure of femoral arteries 
using 5 to 7F procedural sheaths.  The Cardiva Mid-Bore Venous Vascular Closure System (VVCS, 
based on this proven design, are particularly promising in venous closure due to the following: 
o Unimpeded, continual blood flow during closure and bedrest  
o No intraluminal components post closure  
o Naturally resorbed implant material 
The VASCADE VCS arterial platform was evaluated in the RESPECT trial. The study was aimed at 
evaluating safety and efficacy of the extravascular, bioabsorbable closure system.  This was a 
multicenter, randomized comparison of VASCADE VCS versus Manual Compression (MC) in 
Diagnostic (Dx) and Interventional (Ix) patients undergoing femoral access through 6/7 F introducer 
sheaths.  Subjects were randomized 2:1, VASCADE versus MC. 
Endpoints included:   
• 
Time to Hemostasis (TTH)  
• 
Time to Ambulation (TTA)  
• 
Discharge Eligibility (TTDE) 
• 
Time to Discharge (TTD) 
• 
Device and Procedure Success   
• 
Major and Minor Complications 
A total of 420 patients were enrolled (211 Dx, 209 Ix).  Mean age was 62 years with 29% of subjects 
being female.  For Ix patients, 77%/69% (VASCADE/MC) received bivalirudin and 8%/3% received GP 
IIb/IIIa inhibitors. Patients were followed for 30 days. 
 
 

 
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The RESPECT trial demonstrated that the extravascular VASCADE closure device was safe and 
effective compared to manual compression in patients in whom 6 and 7 French femoral access was 
employed in Diagnostic and Interventional procedures.   Despite high percentage of Bivalirudin use 
(77%), there were zero major access site related complications in either arm.  
In addition, the use of VASCADE demonstrated a statistically significant reduction in minor access 
site related complications and significantly shortened TTH, TTA, and time to discharge eligibility 
(TTDE) when compared to MC. 
 
VASCADE Arterial VCS Real World Experience for Venous Closure: 
In the Dou et al (2016) publication, real world experience utilizing the VASCADE arterial VCS for 
venous closure suggests that venous access closure can be accomplished effectively and with 
minimal complications.  
Results for device success were comparable to the Cardiva RESPECT study, where device success 
was defined as the ability to deploy the delivery system, deliver the collagen, and achieve 
hemostasis with the Cardiva VASCADE Vascular Closure System alone or with adjunctive 
compression: 
• 
Dou (2016): 100% per RESPECT criteria 
• 
RESPECT: 96% overall (94% diagnostic & 97% interventional) 
With respect to complications, the Dou (2016) venous study had one device-related minor 
complication per RESPECT criteria and 1 major complication unrelated to the closure device.  
It should be noted that the VASCADE arterial 6/7F device used in Dou (2016) was successful in 
achieving temporary and final hemostasis in venotomies up to 10F, three French sizes above the 
approved indication.    
 
Mid-Bore Venous VVCS vs VASCADE VCS Device Design: 
For the AMBULATE Study, the Cardiva Mid-Bore VVCS catheter’s disc diameter was increased from 
~19F (VASCADE arterial VCS) to ~21 initially and subsequently to ~23F1 to mitigate the device pulling 
through the vessel wall in mid-bore venotomies as a function of venotomy size approaching the 
disc’s diameter.  The disc diameter increase anticipates use of procedure sheaths up to 12F inner 
diameter. 
 
 
1 G170144/S004 5 Day Notice of IDE Change 

 
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1.2. Unmet Clinical Need 
 
Currently, the standard technique for venous closure is manual compression (MC). There are various 
procedures requiring venous access, including procedures that require a single venous access site in 
a single limb up to and including procedures that require multiple venous access sites in both limbs. 
Multi-access site / multi – limb procedures mainly include cardiac ablation.  These cardiac ablation 
procedures account for both the fastest growing segment and majority of venous access 
procedures.   Innovation in the field has progressed cardiac ablations from many hours to a short 
predictable procedure time, however the ongoing requirement for prolonged supine bedrest post-
procedure still results in lengthy delays in time to patient ambulation (TTA).  
 
According to Srivatsa (2015), there are certain limitations with the manual compression approach, 
including: 
1) discomfort and pain for the patient;  
2) postponement of sheath extraction post-procedure which could lead to more discomfort, 
increased bleeding risk and discontinuation of anti-coagulation post-procedure;  
3) risk of deep venous thrombosis; and 
4) risk of failed closure due to inaccurate location of the manual compression site.   
 
1.3. AMBULATE, A Clinical Investigation for Venous Closure [PTL 0508] 
The primary AMBULATE clinical investigational study was focused on multiple venous access site 
closure using the Cardiva Mid-Bore VVCS device for closure following venous catheterization 
procedures to address the greatest clinical need. Data collected during the clinical study suggest that 
there is additional potential for the use of Mid-Bore VVCS to impact other procedural and 
administrative practices to benefit the patient. Additional study is warranted to further evaluate the 
following unmet clinical needs: 
• 
Elimination of Urinary Catheter 
• 
Same Calendar Day Discharge 
• 
Protamine Elimination 
In addition, the AMBULATE study required Investigators to standardize their access practice as 
follows: 
• 
2-access site maximum per limb 
• 
3-access site minimum and 4-access site maximum per patient 
• 
Placement of >9F sheaths in opposite legs 
In real world procedures, there is a wide variety of configurations with respect to the number and 
location (i.e. limb) of femoral venous access sites. 

 
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Elimination of Urinary Catheter  
Urinary catheters can contribute to patient discomfort and are associated with an increased risk of 
Urinary Tract Infection (UTI). Foley catheters which are not indicated for medical reasons (e.g. 
urinary retention or incontinence) are primarily indicated for patients who are expected to be 
placed on longer bedrest. In the AMBULATE Study we learned that there are a variety of practices at 
the site level regarding Foley Use including: exclusive use of urinary catheter; exclusive no urinary 
catheter; and Mixed Use.  
Due to reduced expected bedrest period for VVCS subjects vs. MC subjects, it is expected that the 
use of the urinary catheter is unnecessary for most patients who are receiving the Cardiva Mid-Bore 
VVCS.    
However, in the AMBULATE Study design where subjects were randomized intra-operatively at the 
end of the index procedure, urinary catheter use / non-use was not manipulated as part of the study 
and was dependent on Investigator’s orders (prior to randomization of VVCS vs. MC).  
The AMBULATE CAP Study is a single arm study, therefore Investigators will plan on bedrest orders 
consistent with Mid-Bore VVCS closure for all qualifying subjects. Based on this real-world study 
design, it is expected that a number of subjects not previously considered eligible for No Urinary 
Catheter due to expected prolonged bedrest may now be eligible for elimination of Foley catheter 
for their procedures.  
 
Elimination of Protamine   
In the AMBULATE study treatment arm, as indicated in the protocol1, investigators did not wait for 
heparin reversal using Protamine or wait for target ACT levels in order to close using Mid-Bore VVCS.   
However, as randomization was intra-operative at the end of the index procedure, standard of care 
regarding heparin reversal was followed in the event the subject was randomized to manual 
compression.  
In the AMBULATE CAP Study, however, the single arm study design will allow all qualifying subjects 
to receive Mid-Bore VVCS closure devices. Protamine is unnecessary with the use of Mid-Bore VVCS 
since heparin reversal will occur by natural decay during the bedrest period.   
 
Same Calendar Day Discharge 
In the AMBULATE Study, twenty-eight subjects were discharged on the same calendar day with 
nearly twice as many in the device arm versus the control arm. Specifically, 17/28 subjects (61%) for 
the VVCS arm and 11/28 subjects (39%) for the manual compression arm. Across the 204 study 
 
1 PTL 0508 AMBULATE Protocol Section 7.4.5 Access Site Closure Instructions 

 
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subjects, the majority (166) of subjects (81%) were discharged by the next calendar day for both 
device (76 subjects, 37%) and manual compression (90 subjects, 44%).  
The AMBULATE CAP Study intends to gather additional data in a more defined study group 
populations to expand the potential for low risk patients (i.e. SVT, A-Flutter subjects, or A-Fib & VT 
subjects with CHADS2 Score ≤1) to be discharged the same calendar day as their index procedure. 
1.4. The AMBULATE Continued Access Protocol (CAP) 
 
Overview:  
The AMBULATE CAP study will continue to collect additional data on: 
• 
Urinary Catheter Use 
• 
Same Calendar Day Discharge 
• 
Protamine Use 
In contrast to the primary AMBULATE Study, the AMBULATE CAP study will allow investigators to 
follow their standard access practices rather than protocol-standardized sheath configurations. The 
CAP study design is intended to provide data to support typical clinical practice (e.g. sheath 
configuration) of the Mid-Bore VVCS devices for femoral venous closure in support of the CAP Study.  
Objective:  
The objective of the trial is to demonstrate the safety and effectiveness of the Cardiva Mid-Bore 
Venous Vascular Closure System (VVCS) in sealing femoral venous access sites at the completion of 
catheter-based procedures performed through 6-12 Fr introducer sheath, while allowing for one or 
more of the following: elimination of urinary catheter, elimination of protamine, and/or allowing 
same (calendar) day discharge for the appropriate patient population.  
The AMBULATE CAP Study primary and secondary safety endpoints have the same complication 
definitions as the AMBULATE Study. The primary effectiveness endpoint of Procedure Success for 
this study has the same definition as AMBULATE Procedure Success, specifically, final hemostasis at 
all venous access sites and freedom from major venous access site closure-related complications 
through 30 days follow up. 
Key differences between the randomized AMBULATE study and this CAP study include the following: 
• 
Single Arm Study with prospectively assigned study groups 
• 
No time-based endpoints or data collection 
• 
No Ultrasound Sub-study 
• 
Additional Inclusion/Exclusion Criteria for study groups 
• 
No access site minimum or maximum per limb or per patient 
• 
Allows placement of >9F sheaths in the same leg 
• 
Allows ultrasound as an option to fluoroscopic imaging for disc location verification 
• 
Follow up period is 30 days (+/-10) instead of 30 days (+/-7) 

 
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• 
Follow up can be completed as an office visit or a phone call 
 
It should be noted that there was a development change conditionally approved in G170144/S004 
Device Disc Size Change 5 Day Notice of IDE Change. The disc size manufacturing target was 
increased from 21F to 23F.  There was no change to the product specification for disc diameter; the 
larger size is within the original specification range.  This larger diameter device will continue to be 
used in the AMBULATE CAP Study.  
 
Based on AMBULATE Study preliminary data1, the Mid-Bore VVCS device was effective with no 
significant safety concerns.  The differences between the AMBULATE Study and AMBULATE CAP 
Study reflect learning from the original study and are not expected to introduce additional risks to 
patients.  
 
1.5.  Real World Experience: VASCADE Arterial VCS Real World Experience for Venous 
Closure 
 
In the Dou et al (2016) publication, real world experience utilizing the VASCADE arterial VCS for 
venous closure suggests that venous access closure can be accomplished effectively and with 
minimal complications.  
Results for device success were comparable to the Cardiva RESPECT study, where device success 
was defined as the ability to deploy the delivery system, deliver the collagen, and achieve 
hemostasis with the Cardiva VASCADETM Vascular Closure System alone or with adjunctive 
compression: 
• 
Dou (2016): 100% per RESPECT criteria 
• 
RESPECT: 96% overall (94% diagnostic & 97% interventional) 
With respect to complications, the Dou (2016) venous study had one device-related minor 
complication per RESPECT criteria and 1 major complication unrelated to the closure device.  
It should be noted that the VASCADE arterial 6/7F device used in Dou (2016) was successful in 
achieving temporary and final hemostasis in venotomies up to 10F, three French sizes above the 
approved indication.    
The Cardiva Mid-Bore VVCS catheter’s disc diameter has been increased from ~19F (VASCADE 
arterial VCS) to ~23F to mitigate the device pulling through the vessel wall in mid-bore venotomies 
as a function of venotomy size approaching the disc’s diameter.  The disc diameter increase 
anticipates use of procedure sheaths up to 12F inner diameter. 
 
1 RPT 0527 AMBULATE Sub-study Data Analysis Report for CE Mark 

 
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1.6. Design Verification Testing 
 Design verification testing including the following: 
• Functional  
• Mechanical  
• Biocompatibility  
• Packaging  
• Shelf-life  
• Sterilization 
Conclusion: Based on testing performed, Mid-Bore Venous VCS 6 – 12F successfully fulfilled the 
tests requirements for design verification.  
1.7. Pre-clinical Testing  
Pre-clinical testing included the following two studies: 
• 
Chronic GLP Animal Study [ RPT 0503-01]: safety and efficacy 
• 
Acute Animal Study  [RPT 0533-01]: performance  
 
 Pre-clinical Chronic GLP Study Overview [RPT 0503]  
The purpose of this chronic GLP study was to evaluate the In-Vivo safety and efficacy performance of the 
Cardiva VASCADE 6/7F Vascular Closure System (VCS) in percutaneous closure of femoral veins in the 
porcine model using 12F introducer sheaths.   
• 
High-level Protocol Summary: 
‒ 3 Animals with 6 Devices implanted bilaterally with 12F access sheaths 
‒ ACT >300 seconds 
‒ 30 Day Chronic Study 
‒ Gross Pathology and histopathological analysis was completed on downstream organs and 
venotomy sites  
 
 
Abbreviated High-level Results Summary  
‒ All sites achieved hemostasis within 2 minutes without any complication  
‒ Vessel patency confirmed by ultrasound post collagen deployment 
‒ No gross abnormalities indicative of complications or adverse effects 
‒ Gross evaluation of end organs did not demonstrate any evidence of distal thromboembolic 
events 

 
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‒ Collagen patch was not associated with any type of intraluminal reaction or thrombus 
‒ No adverse effects or complications identified histologically  
 
 
Conclusion: 
‒ Test article met the objectives set forth in study.   
‒ No gross abnormalities indicative of complications or adverse effects associated with the 
test procedure to implant site or organ system.  
‒ Test article sealed veins appropriately using a 12 French introducer sheath and was 
demonstrated to be safe for its intended use.   
 
 Pre-clinical Acute Study Overview [RPT 0533]  
An acute animal study was performed in a porcine model to compare the larger disc device to the 
current device with respect to safety and effectiveness in achieving the intended use.    
A total of 12 cases were performed, 6 per device type. A 9F indwelling sheath was in place for all 
procedures. A 14F sheath along with the 9F indwelling sheath was used for venous access to simulate 
the additional dilation that occurs during a cryo case procedure with 12F sheath access. 
 
The study showed that the larger disc VVCS device offers a greater resistance to disc pull through.  In 
this model, on average, the pull through forces were approximately 24% greater with the larger disc 
device.   Additionally, the study showed that the larger disc VVCS device can be deployed with a 9F 
indwelling sheath with minimal or no distortion to the disc.  Temporary hemostasis was obtained in all 
cases as was evident by lack of any extravasation of contrast in the surrounding tissue.  
 
Therefore, design validation testing demonstrated that device was effective in achieving its intended use 
in venotomies using 14F access sheaths to simulate the 12F access sites with additional dilation as 
observed in the AMBULATE study.  There were no safety issues observed in the study.  
1.8. Clinical Studies   
 AMBULATE Study Mid-Bore VVCS Sub-study analysis for CE Mark [RPT 0527] 
The AMBULATE trial was aimed at evaluating safety and efficacy of the extravascular, bioabsorbable 
closure system, Mid-Bore VVCS.  This was a multicenter, randomized comparison of Mid-Bore VVCS 
versus Manual Compression (MC) patients undergoing femoral venous access through 6-12F 
introducer sheaths.  Subjects were randomized 1:1, VVCS versus MC.  
 
The AMBULATE Study Mid-Bore VVCS Sub-Study analysis was performed using interim data from the 
AMBULATE Study to assess a sub-set of subjects randomized to the treatment arm of the 
AMBULATE Study (PTL 0508-02) with respect to safety and performance of the Cardiva Mid-Bore 
Venous Vascular Closure System (VVCS) in support of CE marking. 

 
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Endpoints included:   
• 
Time to Ambulation (TTA)  
• 
Time to Hemostasis (TTH)  
• 
Discharge Eligibility (TTDE) 
• 
Time to Discharge (TTD) 
• 
Device and Procedure Success   
• 
Major and Minor Complications 
 
Forty (40) consecutive subjects from 5 clinical sites were prospectively enrolled for treatment with 
Mid-Bore VVCS.  Mean age was 63.8 years with 22.5% of subjects being female. Patients were 
followed for 30 days.  Data Analysis results showed the following: 
• 
Performance Endpoints: See Table 1 
• 
Procedure Success and Device Success* : See Table 2 
• 
Safety Endpoints:  There were no major access site related complications and 1 minor 
access site related complication. See Table 3 and Table 4 
 
*Definitions: 
Procedure Success: attainment of final hemostasis at all venous access sites and freedom from 
major venous access site closure-related complications through 30 days. This is a per-patient 
analysis. 
Device Success: the ability to deploy the delivery system, deliver the collagen, and achieve 
hemostasis with the Mid-Bore VVCS. This is a per-access site analysis. 
 
The performance and safety outcomes for the AMBULATE Study Mid-Bore VVCS Sub-analysis of the 
Cardiva Mid-Bore Venous Vascular Closure System (800-612C) demonstrate the performance and 
safety of the device.  The Mid-Bore VVCS successfully closed femoral venous access sites in patients 
who have undergone catheter-based procedures utilizing 6 – 12 Fr procedural sheaths, with single 
or multiple access sites per limb, ranging from a single access site in one limb to multiple access 
sites in both limbs. There were no major access site related complications and 1 minor access site 
related complication.  
 
 
Table 1: Primary Performance Endpoint: TTA for CE Mark Sub Study [RPT 0527-03] 

 
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Time to Ambulation (hours) 
Subjects with 3 
Access Sites 
Subjects with 4 
Access Sites 
All 
Subjects 
N 
11 
29 
40 
Mean 
2.36 
2.75 
2.65 
Std Deviation 
0.50 
1.07 
0.95 
Median 
2.17 
2.24 
2.21 
Min 
2.07 
2.08 
2.07 
Max 
3.68 
6.32 
6.32 
95% Confidence Interval 
2.03-2.70 
2.35-3.16 
2.34-2.95 
 
Table 2: Secondary Performance Endpoint Analysis for CE Mark Sub Study [RPT 0527-03] 
 Description 
N(40) 
Total Post Procedure Time (hours) 
 
N 
40 
Mean 
2.91 
Std Deviation 
0.99 
Median 
2.48 
Min 
2.25 
Max 
6.63 
95% Confidence Interval 
2.59-3.23 
 
 
Time to Closure Eligibility (minutes) 
 
N 
40 
Mean 
6.49 
Std Deviation 
3.00 
Median 
6.59 
Min 
1.60 
Max 
13.55 
95% Confidence Interval 
5.53-7.45 
 
 
Time to Hemostasis (minutes) 
 
N 
149 
Mean 
6.08 
Std Deviation 
3.40 
Median 
5.17 
Min 
3.00 
Max 
28.73 
95% Confidence Interval 
5.53-6.63 
  
 

 
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 Description 
N(40) 
Time to Discharge Eligibility (hours) 
 
N 
40 
Mean 
2.92 
Std Deviation 
0.94 
Median 
2.50 
Min 
2.30 
Max 
6.48 
95% Confidence Interval 
2.62-3.22 
  
 
Time to Hospital Discharge (hours) 
 
N 
40 
Mean 
21.6 
Std Deviation 
11.95 
Median 
22.52 
Min 
3.82 
Max 
75.75 
95% Confidence Interval 
17.78-25.42 
 
 
 
Table 3: Major Access Site Related Complications - Total Number of Limbs with Any Number of 
Occurrences 
(N=78) 
Number 
Percent 
Combined major venous access site closure-related complications 
through 30 days post-procedure 
0 
0% 
Individual major venous access site closure-related  
complications through 30 days post-procedure 
Access site-related bleeding requiring transfusion; 
0 
0% 
Vascular injury requiring surgical repair;  
0 
0% 
Access site-related infection confirmed by culture and 
sensitivity, requiring intravenous antibiotics and/or 
extended hospitalization; 
0 
0% 
New onset permanent access site-related nerve injury (i.e., 
persisting for > 30 days) 
0 
0% 
New onset access site-related nerve injury in the ipsilateral 
lower extremity requiring surgical repair; 
0 
0% 
Pulmonary embolism requiring surgical or endovascular 
intervention and/or resulting in death, to be confirmed by 
CT pulmonary angiography, lung ventilation/perfusion scan 
(VQ scan) or autopsy;  
0 
0% 

 
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The AMBULATE CAP Study           CONFIDENTIAL                          PTL 0543-02          CIP  Page 24 of 67 
  
 
 
(N=78) 
Number 
Percent 
Pulmonary embolism NOT requiring surgical or 
endovascular intervention and/or NOT resulting in death, 
to be confirmed by CT pulmonary angiography or lung 
ventilation/perfusion scan (VQ scan). 
0 
0% 
Primary Safety 95% Confidence Interval 
95.4%-100% 
 
 
Table 4: Minor Access Site Related Complications - Total Number of Limbs with Any Number of 
Occurrences 
(N=78) 
Number 
% 
Combined minor venous access site closure-related complications 
through 30 days post-procedure 
1 
1.3% 
Individual minor venous access site closure-related  
complications through 30 days post-procedure 
Access site-related bleeding requiring greater than 30 
minutes of continuous manual compression to achieve 
initial venous hemostasis; 
0 
0% 
Access site-related hematoma > 6 cm documented by 
ultrasound 
0 
0% 
Late access site-related bleeding (following hospital 
discharge) 
0 
0% 
Ipsilateral deep vein thrombosis, confirmed by 
ultrasound/imaging 
0 
0% 
Localized access site infection confirmed by culture and 
sensitivity, treated with intramuscular or oral antibiotics 
1 
1.3% 
Arteriovenous fistula requiring treatment  
0 
0% 
Arteriovenous fistula not requiring treatment 
0 
0% 
Pseudoaneurysm requiring thrombin injection, fibrin 
adhesive injection or ultrasound-guided compression 
0 
0% 
Pseudoaneurysm not requiring treatment 
0 
0% 
Transient access site-related nerve injury 
0 
0% 
Secondary Safety 95% Confidence Interval 
93.1%-100% 
 
 RESPECT Trial using VASCADE arterial VCS   
VASCADE 6/7F VCS was evaluated in a prospective, multi-center, randomized (2:1) clinical trial (the 
RESPECT Trial) in 20 sites in the United States and one site in Australia, comparing VASCADE VCS to 
Manual Compression (MC). The trial involved 420 patients undergoing diagnostic (n = 211) or 

 
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The AMBULATE CAP Study           CONFIDENTIAL                          PTL 0543-02          CIP  Page 25 of 67 
  
 
 
interventional (n = 209) endovascular procedures, with 275 of those subjects receiving the VACADE 
device.  
The RESPECT trial was designed to evaluate the safety and effectiveness of the VASCADE 6/7 Fr VCS in 
sealing femoral arterial access sites. It was specifically designed to demonstrate a reduction in 
hemostasis, ambulation, and eligibility for hospital discharge in comparison to manual compression.   
Table 3 and Table 4 summarize safety and efficacy data from the RESPECT study.  
 Since commercial release in 2013, real-world experience with over 124,000 devices sold in the US, the 
data indicates the ongoing relevance of the clinical trial results (Tables 5, 6): 
• 
0.36%  Reported Complaint Rate  
• 
0.1%   Reported Patient Complication Rate  
The VASCADE VCS platform has an established safety track record in controlled clinical settings and real 
world usage.  VASCADE VCS’s safety profile has been established in arterial vessel closure, which 
generally provides a more difficult closure environment compared to venous closure due to higher 
blood pressure.  
 
Table 5: Access Site-Related Complications at 30 Days by Event 
 
Total 
(N=417) 
VASCADE 
(N=275) 
Manual 
Compression 
(N=142) 
p-value* 
Any Access Site-Related Major Complication 
0 
0.0% 
0 
0.0% 
1.00 
Access site-related bleeding requiring transfusion 
0 
0.0% 
0 
0.0% 
1.00 
Vascular injury requiring repair 
0 
0.0% 
0 
0.0% 
1.00 
New ipsilateral lower extremity ischemia causing a threat to the viability of 
the limb 
0 
0.0% 
0 
0.0% 
1.00 
Access site-related infection requiring intravenous antibiotics and/or 
extended hospitalization 
0 
0.0% 
0 
0.0% 
1.00 
New onset access site-related neuropathy in the ipsilateral lower extremity 
requiring surgical repair 
0 
0.0% 
0 
0.0% 
1.00 
Permanent access site-related nerve injury (> 30 days) 
0 
0.0% 
0 
0.0% 
1.00 
Any Access Site-Related Minor Complication 
3 
1.1% 
10 
7.0% 
0.002 
Access site-related bleeding requiring > 30 minutes to achieve hemostasis 
1 
0.4% 
10 
7.0% 
0.0001 
Access site-related hematoma > 6 cm 
1 
0.4% 
0 
0% 
1.00 
Late access site-related bleeding (following hospital discharge) 
0 
0% 
0 
0% 
1.00 
Ipsilateral lower extremity arterial emboli 
0 
0% 
0 
0% 
1.00 
Ipsilateral deep vein thrombosis** 
4 
1.5% 
0 
0% 
NA 
Access site-related vessel laceration 
0 
0% 
0 
0% 
1.00 
Access site wound dehiscence 
0 
0% 
0 
0% 
1.00 
Localized access site infection treated with intramuscular or oral antibiotics 
0 
0% 
0 
0% 
1.00 
Arteriovenous fistula not requiring treatment** 
1 
0.4% 
0 
0% 
NA 
Pseudoaneurysm requiring thrombin injection or fibrin adhesive injection** 
1 
0.4% 
0 
0% 
NA 

 
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Pseudoaneurysm not requiring treatment** 
4 
1.5% 
0 
0% 
NA 
New onset access site-related neuropathy in the ipsilateral lower extremity 
not requiring surgical repair 
1 
0.4% 
0 
0% 
1.00 
Ipsilateral pedal pulse diminished by two grades or transiently lost 
0 
0% 
0 
0% 
1.00 
*Two-sided Fisher's exact test 
**Due to different complication-detecting methods between study arms (100 VASCADE patients and no other study patients 
underwent a femoral ultrasound exam in an ultrasound sub-study), rates for pseudoaneurysm requiring or not requiring 
treatment, arteriovenous fistula not requiring treatment, and ipsilateral deep vein thrombosis (which were detected by 
ultrasound exam) are presented but not compared between arms, nor are they included in the computation of the VASCADE 
overall minor complication rate (top row). 
 

 
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Table 6: RESPECT Efficacy Endpoint Results 
Total N=420 
VASCADE 
(N=278) 
Manual 
Compression 
(N=142) 
p-value* 
Time to Hemostasis (minutes) 
  
  
  
N 
275 
142 
 
Mean 
4.8 
21.4 
< 0.0001 
Std Deviation 
5.4 
12.4 
 
Median 
3.0 
20.0 
< 0.0001 
Min 
0.6 
0.0 
 
Max 
31.6 
97.0 
 
  
  
  
  
Time to Ambulation (hours) 
  
  
  
N 
275 
142 
 
Mean 
3.8 
5.8 
< 0.0001 
Std Deviation 
5.1 
3.1 
 
Median 
3.2 
5.2 
< 0.0001 
Min 
1.0 
1.7 
 
Max 
78.0 
22.8 
 
  
  
  
  
Time to Discharge Eligibility (hours) 
  
  
  
N 
274 
142 
 
Mean 
4.8 
6.5 
0.001 
Std Deviation 
6.4 
3.3 
 
Median 
3.6 
5.7 
< 0.0001 
Min 
1.4 
2.2 
 
Max 
78.4 
23.2 
 
  
  
  
  
Time to Hospital Discharge (hours) 
 
 
 
N 
275 
142 
 
Mean 
18.3 
13.7 
0.04 
Std Deviation 
34.5 
9.8 
 
Median 
17.2 
13.9 
0.94 
Min 
1.7 
2.4 
 
Max 
432.9 
55.6 
 
*p-value from t-test for comparing means and Wilcoxon's test for comparing medians 
 
 

 
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1.9. Risks and Benefits 
 Risks 
Risks associated with the Cardiva Mid-Bore VVCS are similar to those associated with 
other extravascular methods of achieving hemostasis at venotomy sites.  Complications 
that may occur include:  
• 
Allergic response  
• 
Arterio-venous fistula  
• 
Bleeding/oozing from the puncture site 
• 
Bruising at puncture site 
• 
Death 
• 
Deep vein thrombosis 
• 
Device failure / malfunction 
• 
Edema 
• 
Embolization (thrombus, air, calcific debris, device)  
• 
Hematoma 
• 
Infection 
• 
Inflammatory response 
• 
Intimal tear / dissection 
• 
Laceration of the vessel wall 
• 
Lower extremity ischemia 
• 
Peripheral nerve injury 
• 
Perforation of the vessel wall 
• 
Pseudoaneurysm 
• 
Pulmonary embolism 
• 
Puncture site pain 
• 
Retroperitoneal bleeding  
• 
Superficial vein thrombosis 
• 
Vasovagal response 
• 
Vascular injury 
• 
Vessel occlusion 
• 
Vessel thrombus  
• 
Wound dehiscence 
 Benefits 
The potential benefits of using the Cardiva Mid-Bore VVCS to achieve venous hemostasis include 
elimination of urinary catheter use, same calendar day discharge, and protamine elimination, 
which the trial is intended to evaluate, while maintaining an acceptable safety profile. 

 
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2. Device Description 
 
The Cardiva Mid-Bore Venous Vascular Closure System (VVCS) is indicated for the percutaneous 
closure of femoral venous access sites while reducing times to ambulation and discharge 
eligibility in patients who have undergone catheter-based procedures utilizing 6 – 12 Fr 
procedural sheaths, with single or multiple access sites per limb, ranging from a single access site 
in one limb to multiple access sites in both limbs. 
The Cardiva Mid-Bore VVCS is a disposable device based on the previously approved VASCADE 
6/7F arterial VCS device. The only significant change with respect to the approved device is an 
increase in disc diameter from ~19F to ~23F to ensure temporary hemostasis and proper collagen 
deployment during closure of larger bore holes.   
As in the previously approved device, the Mid-Bore VVCS device is designed to deliver a 
resorbable collagen patch extravascularly to block blood flow from the femoral venotomy site at 
the completion of a catheterization procedure.  Cardiva’s Mid-Bore VVCS devices are intended to 
assist physicians or catheter lab technicians in controlling bleeding from femoral venotomy sites 
and reduce time to ambulation. 
The Mid-Bore VVCS device is used in conjunction with 6 – 12 Fr inner diameter introducer 
sheaths.  The VVCS device is introduced through a compatible procedure sheath at the 
completion of a catheterization procedure.  
The Mid-Bore VVCS is comprised of a catheter containing a resorbable collagen implant. Refer to 
Figure 1 below for an image of the device.  
 
Figure 1: Cardiva Mid-Bore VVCS with Disc Deployed 
 
 
To use the Cardiva VVCS, the catheter is inserted into the femoral vein through the previously 
placed introducer sheath.  After insertion, the distal tip of the catheter is deployed, opening and 

 
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expanding a low-profile Nitinol (NiTi) disc within the lumen of the femoral vein.  The introducer 
sheath is then removed from the vessel over the catheter and the low-profile disc is placed 
against the inner wall, locating the vessel wall and temporarily sealing the venotomy.  The 
position of the device disc against the vessel wall locates the collagen patch in the tissue tract 
immediately adjacent to the venotomy site (extravascular) and its location is verified using 
fluoroscopy prior to release.  The clip is placed on the device shaft at the surface of the skin to 
hold the device in place during fluoroscopy. 
Note, the principle of operation and the steps described below are identical to that of the 
previously approved device. Refer to the Instructions For Use document in Attachment 3. 
Device Labeling 
A copy of the Instructions for Use (IFU) will be included with the devices.  The Cardiva Mid-Bore 
Venous Vascular Closure System (VVCS) labels contain the following information:  
• 
Venous Vascular Closure System 
• 
Lot number  
• 
Expiration (use by) date 
• 
For Investigational Use Only 
3. AMBULATE CAP Study Objective 
The objective of the trial is to demonstrate the safety and effectiveness of the Cardiva Mid-Bore Venous 
Vascular Closure System (VVCS) in sealing femoral venous access sites at the completion of catheter-based 
procedures performed through 6-12 Fr introducer sheath, while allowing for one or more of the following: 
elimination of the urinary catheter, elimination of protamine, and/or allowing same (calendar) day 
discharge for the appropriate patient population.  
4. Study Design 
4.1. Overview 
This is a prospective, multi-center, single-arm continued access clinical trial designed to evaluate 
the safety and effectiveness of the Cardiva Mid-Bore Venous Vascular Closure System (VVCS) in 
sealing multiple femoral venous access sites at the completion of catheter-based procedures 
performed through 6 - 12 Fr introducer sheaths.  Measures of safety and effectiveness will be 
assessed through hospital discharge and 30 (±10) days post-procedure.   
4.2. Sample Size 
Enrollment: 300 subjects will be included in this trial. Subjects will be considered enrolled in 
intra-procedural timeframe based on the inclusion/exclusion criteria previously identified.  
Investigational Sites: This trial will be conducted at up to 5 sites in the United States, with a 
minimum of 2 sites enrolling subjects in the trial. Any one site will not enroll more than 60% of 
the subjects. The sites will be sites that participated in the AMBULATE Study. 

 
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5. Study Population 
5.1. Selection Criteria 
The following pages outline the specific inclusion and exclusion criteria for the study. Before the 
study randomization, a patient must meet all of the inclusion and exclusion criteria. 

 
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 Pre-Operative Inclusion Criteria 
Pre-Operative 
Inclusion 
Criteria 
All subjects are required to meet the following inclusion criteria in order to be considered 
eligible for participation in this trial: 
1. ≥18 years of age; 
2. Capable and willing to give informed consent; 
3. Acceptable candidate for an elective, non-emergent catheter-based procedure via the 
common femoral vein(s) using a 6 to 12 Fr inner diameter introducer sheath  
4. Able and willing to complete a 30 (± 10) days post-procedure follow-up contact; 
5. Acceptable candidate for emergent vascular surgery, and/or manual compression of 
the venous access site; 
6. Study Group Criteria: The subject is eligible for at least one of the following study 
groups:  
• 
Same Calendar Day  Discharge Candidate:  
• 
The subject is expected to undergo an Atrial Fibrillation, Supraventricular 
Tachycardia, Ventricular Tachycardia or Atrial Flutter procedure.    
• 
If procedural heparin is planned to be used, it must be reversed at or before 
venous closure.  
• 
Physician or designee is expected to be on site for discharge evaluation. 
• 
Supraventricular Tachycardia (SVT) or Atrial Flutter Subjects: No Additional 
Criteria  
• 
Atrial Fibrillation or Ventricular Tachycardia Procedure Subjects: CHADS2 
Score must be ≤1: 
CHADS 2 Score: Stroke Risk Assessment in Atrial Fibrillation 
Score 
CHADS2 Risk Criteria 
1 point 
C: Congestive heart failure 
1 point 
H: Hypertension 
1 point 
A: Age ≥ 75 years 
1 point 
D: Diabetes mellitus 
2 points 
S: Stroke / transient ischemic attack / 
thromboembolism 
b) No Urinary Catheter Candidate:  
• 
The subject is a candidate to undergo the procedure and bedrest without a 
urinary catheter (i.e., indwelling, condom or straight catheter insertion). 
• 
No history of urinary retention due to e.g. anesthesia, prostate issues, etc.  
c) No Protamine Candidate: The subject is a candidate to receive procedural 
heparin for anti-coagulation management. 
Note: 
Initial subject eligibility will be determined based on pre-operative screening.  
Final subject enrollment in one or more study groups will be determined at the end the 
procedure based on general intra-op exclusion criteria, as well as group-specific 
criteria.  Enrollment is thus determined intra-operatively, at the end of the case. 
 

 
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 Pre-Operative Exclusion Criteria 
Pre-Operative 
Exclusion 
Criteria 
Subjects will be excluded from participating in this study if they meet any of the 
following criteria prior to initiation of the index procedure: 
1.  Advanced refusal of blood transfusion, if it should become necessary; 
2. Active systemic infection, or cutaneous infection or inflammation in the vicinity of 
the groin; 
3. Pre-existing immunodeficiency disorder and/or chronic use of high dose systemic 
steroids; 
4. Known history of bleeding diathesis, coagulopathy, hypercoagulability, or current 
platelet count < 100,000 cells/mm3; 
5. Severe co-existing morbidities, with a life expectancy of less than 12 months; 
6. Currently involved in any other investigational clinical trial that may interfere with 
the outcomes of this study in the opinion of investigator; 
7. Femoral arteriotomy in either limb with any of the following conditions: 
a. access within < 10 days 
b. any residual hematoma, significant bruising, or known associated vascular 
complications 
c. use of a vascular closure device within the previous 30 days; 
8. Femoral venotomy in either limb with any of the following conditions: 
a. access within < 10 days 
b. any residual hematoma, significant bruising, or known associated vascular 
complications 
c use of a vascular closure device  
9. Any planned procedure involving femoral arterial or venous access in either limb 
within the next 30 days; 
10. Any history of deep vein thrombosis, pulmonary embolism or thrombophlebitis;  
11. Significant anemia with a hemoglobin level less than 10 g/dL or a hematocrit less 
than 30%; 
12. Females who are pregnant, planning to become pregnant within 3 months of the 
procedure, or who are lactating; 
13. Extreme morbid obesity (BMI greater than 45 kg/m2) or underweight (BMI less than 
20 kg/m2); 
14. Unable to routinely walk at least 20 feet without assistance; 
15. Known allergy/adverse reaction to bovine derivatives; 
16. Administration of low molecular weight heparin (LMWH) within 8 hours before or 
after the procedure; 
17. Planned procedures or concomitant condition(s) that may extend ambulation 
attempts beyond 2-3 hours, and/or hospitalization time (e.g., staged procedure, 
serious co-morbidity), in the opinion of the Investigator. 
 
 

 
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 Intra-Operative Inclusion Criteria 
Intra-
Operative 
Exclusion 
Criteria 
Subjects will be excluded from participating in this study if any of the following 
exclusion criteria occur during the index procedure: 
 
General Intra-op Exclusion Criteria: 
1. Any attempt at femoral arterial access during the procedure; 
2. Any procedural complications that may extend routine recovery, ambulation and 
discharge times; 
3. If the physician deems that a different method should be used to achieve 
hemostasis of the venous access sites, or that the subject should not attempt 
ambulation according to the protocol requirements; 
4. All venous access sites may must comply with the following exclusion criteria, 
assessed immediately prior to enrollment: 
d. Difficult insertion of procedural sheath or needle stick problems at the onset 
of the procedure (e.g., multiple stick attempts, accidental arterial stick with 
hematoma, “back wall stick”, etc.) in any of the study veins; 
e. A procedural sheath < 6 Fr or > 12 Fr in inner diameter is present at time of 
closure; 
f. A procedural sheath > 12 Fr inner diameter at any time during the procedure. 
d. Venous access site location is noted to be “high”, above the inguinal ligament 
(cephalad to lower half of the femoral head or the inferior epigastric vein origin 
from the external iliac vein); 
e. Intra-procedural bleeding around sheath, or suspected intraluminal thrombus, 
hematoma, pseudoaneurysm, or AV fistula; 
f. Length of the tissue tract, the distance between the anterior venous wall and 
skin, is estimated to be less than 2.5 cm. 
 

 
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 Intra-Operative Inclusion Criteria 
Additional 
Intra-
Operative 
Screening: 
Inclusion 
Criteria  
 
Study Group Criteria: The subject must be eligible for at least one of the following study 
groups:: 
 
a) Same Calendar Day  Discharge (all criteria apply): 
• 
In the Investigator’s opinion, the subject is a candidate for Same Calendar Day 
Discharge per protocol.  
• 
If procedural heparin is used, it must be reversed at or before venous closure.  
• 
Physician must be on site for discharge evaluation. 
• 
Supraventricular Tachycardia (SVT) or Atrial Flutter Subjects: No Additional 
Criteria  
• 
Atrial Fibrillation or Ventricular Tachycardia Procedure Subjects: CHADS2 
Score is ≤1, as assessed pre-operatively. 
o The subject is not enrolled in the No Protamine Group. 
 
CHADS 2 Score: Stroke Risk Assessment in Atrial Fibrillation 
Score 
CHADS2 Risk Criteria 
1 point 
Congestive heart failure 
1 point 
Hypertension 
1 point 
Age ≥ 75 years 
1 point 
Diabetes mellitus 
2 points 
Stroke/transient ischemic attack 
 
b) No Urinary Catheter:  
• 
The subject does not have a urinary catheter inserted/indwelling at the end of 
the procedure, just prior to enrollment. 
 
c) No Protamine:  
• 
The subject received procedural heparin for anti-coagulation management and 
did not/will not receive protamine. 
• 
The subject is not enrolled in the Same Calendar Day Discharge Group 
 
*a subject may not be co-enrolled in Same Calendar Day Discharge and No Protamine 
study groups.  
 
5.2. Withdrawal of Subjects 
While study withdrawal is discouraged, subjects may withdraw from the study at any time, with 
or without reason and without prejudice to further treatment. In all cases of withdrawal, the 
reason(s) for withdrawal (if given) will be recorded upon study termination. In addition, the 
Investigator may withdraw the subject for any other reason determined by the Investigator to 
be in the best interest of the subject. 

 
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Subjects who are intended to receive VVCS and then never have any device(s) inserted, for any 
reason, will not be enrolled in the study. Screen failure data will be recorded on the log. 
6. Written Informed Consent  
Written Informed Consent must be obtained for all patients who are potential study candidates.  
Patients who meet pre-op inclusion/exclusion entry criteria will be invited to participate, and asked 
to sign the study-specific, Institutional Review Board (IRB)-approved Informed Consent form before 
any study-specific tests or procedures are performed. Study personnel should explain that even if a 
patient agrees to participate in the study and signs an informed consent form, the Investigator may 
determine that the patient is not a suitable candidate for the study.  
A Screening/Enrollment Log will be maintained to document select information about candidates 
who fail to meet the entry criteria.  
7. Study Procedures and Enrollment 
7.1. Duration of Subject Participation 
Subjects enrolled in the trial will participate for approximately 30 days +/- 10 days. 
7.2. Enrollment 
Prior to the procedure, subjects will be screened for eligibility in each of the three study groups. 
Subjects must be eligible for at least one of the groups to be eligible for enrollment and may be 
eligible to participate in multiple groups. All subjects who are eligible for participation will 
undergo additional screening at the end of the procedure, prior to enrollment, to determine 
their participation in that study group. Note that subjects may not participate simultaneously in 
the No Protamine and Same Calendar Day Discharge Groups for potential safety reasons. 
At the completion of the procedure, subjects that meet all the intra-operative eligibility criteria 
and who receive any portion of a Cardiva Mid-Bore VVCS are considered enrolled in the study. 
Subjects must have at least one device inserted into the sheath/body to be considered enrolled 
and subsequently must complete all study requirements. If a subject has all venous access sites 
closed with manual compression only for any reason, and did not ever have a Cardiva VVCS 
device inserted, he/she will not be enrolled in the study at all. Subjects who have at least one 
Cardiva VVCS device inserted should have as many venous access sites closed with VVCS as 
possible (i.e., “conversion” to manual compression should only occur when it is not feasible to 
close a site with VVCS). See Section 5.2 Withdrawal of Subjects.  
 
 

 
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7.3. Visit Schedule 
The following outlines the required study assessments. 
Table 7.  Study Event Schedule 
 
< 45 days 
before 
Procedure 
 
Procedure 
Post-
Procedure/ 
Successful 
Ambulation 
Post-
Procedure/ 
Hospital 
Discharge 
30 days +/- 10 
days Contact 
Study Initiation: 
X 
 
 
 
 
 
Demographics/ Medical History 
X 
 
 
 
 
Groin assessment 
 
X 
X 
X 
X 
Complaints of pain/nerve injury in 
lower extremities 
X 
 
 
X 
X 
Laboratory Tests*: 
X 
 
 
 
 
Pre-op Inclusion / Exclusion Criteria 
Assessment 
X 
X 
 
 
 
Informed Consent 
X 
 
 
 
 
Intra-procedural Inclusion Criteria  
 
X 
 
 
 
Intra-procedural Exclusion Criteria 
Assessment 
 
X 
 
 
 
Enrollment 
 
X 
 
 
 
Data Collection: 
 
 
 
 
 
Hemostasis Confirmation 
 
X 
 
 
 
Ambulation Date/Time 
 
 
X 
 
 
PES - Pt. Experience Survey 
 
 
X 
 
 
Same Calendar Day  Discharge 
Eligibility Assessment 
 
 
X 
 
 
Discharge Date/Time 
 
 
 
X 
 
Pain Medication Use 
 
X 
X 
X 
 
Anti-coagulant/Anti-platelet use 
X 
X 
 
 
 
Study Endpoint Data Collection: 
 
 
 
 
 
All groups: Procedure success 
 
X 
 
 
X 
All groups: Device Success 
 
X 
 
 
 
Same Calendar Day Discharge: 
Study group success 
 
 
 
X 
X1 
No Urinary Catheter: Study group 
success 
 
X 
X 
 
 
No Protamine: Study group 
success 
 
X 
X 
 
 
Adverse Events 
 
X 
X 
X 
X 
*For subjects on warfarin, document most recent INR prior to the procedure 
1 No re-admission for access site-related complications within 72 hours of discharge. 
 

 
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7.4. Study Procedures 
 Pre-Operative 
Prior to the subject’s scheduled procedure, obtain a medical history and record the subject’s 
demographic data (age, race, ethnicity, and gender) and baseline information (height, weight, 
BMI).  Review the Pre-operative Inclusion and Exclusion criteria within 45 days prior to the 
planned procedure date, including collection of the following routine blood tests: 
• platelet count 
• hemoglobin and hematocrit 
Review of the subject’s medical history and risk factors will be documented. The subject will be 
asked about any pre-existing lower extremity nerve complaints in both lower limbs (i.e., 
symptoms, severity). Current medication regimen that that may affect bleeding (e.g., anti-
platelet, anti-coagulant, anti-thrombotic agents, etc.) will be documented. 
 Intra-Operative – Data Collection for All Subjects 
For consented subjects that continue to meet the Pre-operative Eligibility Criteria, record the 
following data regarding their procedure:  
• 
procedure type: A-Fib, A-Flutter, SVT, VT, LAA, Other 
• 
ablation modality (e.g., RF, Cryo) 
• 
number and limb location of access sites (left/right) 
• 
techniques used to gain venous access, if any (e.g., ultrasound, micropuncture) 
• 
procedural anti-coagulation administered 
• 
uninterrupted anti-coagulation protocol, if applicable 
• 
final procedural ACT time and value, if applicable 
• 
protamine administration, dose and time (if applicable per study group, and if given) 
• 
Urinary catheter use 
 Intra-Operative – Access Site Requirements 
The following procedural requirements apply to all subjects enrolled in this study: 
• 
All access sites must have procedural sheaths with a minimum of a 6 Fr and a maximum of a 
12Fr sheath inner diameter at the end of the case. 
• 
Refer to the Cardiva Mid-Bore VVCS IFU for specific instructions on device use. 
 Intra-Operative - Subject Identification 
At the end of the catheter-based procedure, with the procedural sheaths in place and under 
fluoroscopic1 or ultrasound visualization, assess sheath placement and the anatomy of all 
venous access sites to verify the intra-operative eligibility criteria prior to randomization. Each 
 
1 Note: For fluoroscopy, an injection of contrast will be made. 

 
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venous access site must meet all intra-procedural access site-specific criteria for the subject to 
be eligible. 
Once it has been determined that the subject does not meet any of the general intra-operative 
exclusion criteria, and that none of the venous access sites meet the specific access site 
exclusion criteria (i.e., all venous access sites must meet all study criteria for the subject to be 
eligible), then the subject is eligible for enrollment. The following hierarchal Study Group 
screening should be performed at this time, to ensure that a subject has met eligibility for 
enrollment into at least one of the Groups: 
• 
Study Group Assignment (in hierarchal order): 
o Same Day Calendar Discharge Group:  Final determination of eligibility for Same 
Calendar Day Discharge should be determined. These subjects require protamine 
administration, therefore cannot be simultaneously enrolled in the No Protamine 
Group. 
o No Protamine Group: If subject is NOT a candidate for Same Calendar Day 
Discharge, he/she should then be screened for eligibility in the No Protamine Group 
(i.e., no protamine administered for subjects who received anti-coagulants during 
the case).  
o No Urinary Catheter Group: If the subject was determined to have been a candidate 
for the No Urinary Catheter Group per Pre-procedural Inclusion Criteria, and the 
subject did not have a urinary catheter inserted pre-procedure, they will be enrolled 
in that Group when enrolled into the study. These subjects may be co-enrolled with 
either of the other 2 Study Groups.  
• 
Once Study Group assignment has been determined, and a device has been inserted into 
the sheath, the subject is enrolled, and every femoral venous access site should be closed 
using the Mid-Bore VVCS. 
• 
Study data will be captured according to the instructions below. 
• 
NOTE: Any subject that meets final eligibility criteria and receives any portion of a Mid-
Bore VVCS is considered to be enrolled, and all peri-procedural study data must be 
collected under the Intent to Treat principle. For this reason, it is imperative that final 
eligibility criteria are confirmed prior to first device insertion. 
• 
If the subject receives a Mid-Bore VVCS and it is subsequently discovered that one or more 
of the access sites is not able to be closed (e.g., complication), apply manual compression 
to the affected access sites and close all eligible access sites using Mid-Bore VVCS. All 
study data will still be collected for the subject. See Section 5.2 Withdrawal of Subjects. 
 Access Site Closure Instructions 
The following process will be used to collect procedural data: 

 
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The Mid-Bore VVCS, the device should be deployed according to procedure in the Instructions 
for Use (IFU) provided in Attachment 3.  
Document device information: 
• Device Lot # 
• Device Success evaluation 
• Document any complications or device performance issues on the Closure Procedure eCRF; 
refer to the Manual of Operations for device return instructions in the case of any device 
performance issues.  
If the subject is unable to receive the Mid-Bore VVCS and instead must receive manual 
compression, it should be performed according to the institution’s standard practice. If 
protamine is administered, the Investigator should follow institutional practice guidelines for re-
checking ACT levels and/or waiting a specified time or for a target ACT value prior to removal of 
sheaths and application of manual compression.  
Documenting Access Site Hemostasis: 
While performing the procedure, record the following information1: 
• 
For each subject, record: 
• Number of femoral venous access sites on each side 
• Final introducer sheath size (inner diameter and length) at time of closure (i.e. after final 
sheath exchanges) 
• Hemostasis Confirmation: Document overall/final venous hemostasis was confirmed 5 
minutes after final access site hemostasis. The bedrest timing begins at hemostasis 
confirmation (e.g., bedrest for 2 hours from this time). 
Note: For VVCS, formation of a hematoma post-sheath removal may indicate a back-wall or 
secondary venous or arterial puncture.  If this situation is suspected, the VVCS should be removed 
and the subject should be converted to manual compression at that location. Additional access 
sites may still be closed with Mid-Bore VVCS, as appropriate. 
 Post-Operative 
After hemostasis is achieved and confirmed after 5 minutes, the access sites should be 
monitored for all subjects according to site’s standard practices.  
Post-procedure, record the following information between the time of transfer out of the lab 
and initial successful ambulation: 
 
• 
Any medication administered for management of pain while the subject is on initial bedrest 
will be collected (up until time of successful ambulation). 
 
1 source worksheets will be provided by Sponsor 

 
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Ambulation Guidelines, all Subjects  
Bed rest orders guidance for successful VVCS closure for subjects with 3 to 4 access sites is 2 to 
2.5 hours after final venous hemostasis is achieved. Bedrest for other closure scenarios could be 
shorter (e.g., 1 VVCS access site) or longer (e.g., conversion to manual compression of one or 
more access sites, etc.) as ordered, per Investigator discretion. Following bedrest, the subject is 
ambulated if stable. Check the groin immediately post-ambulation.  Re-check groin per 
institution’s standard of care to verify status.  Any delay in ambulation (i.e., >1 hour beyond 
physician’s orders) and reason will be documented (e.g., pt. is sleeping, no staff available). After 
the subject has successfully completed the ambulation assessment, all access sites should be 
carefully assessed for the following and documented: 
• 
Forming or expanding hematoma 
• 
Presence of any obvious vascular complications at the access site. 
If the subject does not exhibit any of these symptoms at any of the access sites within 20 
minutes, he/she may be considered to have successfully ambulated. 
If there is any sign of active bleeding at the access site(s) after ambulation, measures should be 
taken to re-achieve hemostasis and then the subject re-ambulated when the Investigator 
determines that it is appropriate to do so. In these cases, ambulation will be repeated and 
documented when successful, and the re-bleeding will be documented as an adverse event. 
NOTE: If one or more of the access sites are not able to be closed with the Mid-Bore VVCS (e.g., 
complication preventing use of the device, user error), subjects should be maintained on 
bedrest according to the Investigator’s discretion. This would not constitute a deviation from 
the protocol.  
Discharge Eligibility Guidelines (Same Calendar Day Discharge subjects only): 
Subjects enrolled in the Same Calendar Day  Discharge Group should be evaluated for potential 
same day discharge after successful ambulation has been achieved. If they are considered stable 
and eligible, attempts should be made to achieve discharge before midnight. If the subject is not 
deemed eligible, the reason will be documented and the subject should be discharged according 
to the physician’s discretion. The Investigator may delegate this assessment to qualified medical 
personnel, based on institution’s standard practices.  
 
Patient Experience Survey Administration Guidelines [Attachment 4]  
A Patient Experience Survey will be administered to all subjects after successful Ambulation, to 
characterize their experience while on bedrest post-procedure. The Research designee should 
confirm the responses are complete, according to the Instructions provide in the Manual of 
Operations. These data will be entered in the eCRF but will not be included in endpoint analyses. 
Discharge Guidelines (all subjects): 

 
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Prior to hospital discharge, all subjects will be asked about any lower extremity nerve 
complaints in both lower limbs (i.e., symptoms, severity) that were not existing prior to the 
index procedure. The data will be captured in the Case Report Forms.  
The discharge date and time will be recorded. Research personnel should attempt to confirm a 
date for a follow-up contact at 30 (+/-10) days with the subject prior to discharge to ensure 
compliance.  
Any medication administered for management of pain between the time of successful 
ambulation and hospital discharge will be recorded. 
Documentation of Venous Re-Bleeding at Femoral Access Site: 
If a subject experiences venous re-bleeding at any of the femoral venous access sites after a) 
hemostasis had been confirmed for at least 5 minutes and b) prior to hospital discharge, 
document the following information on the Discharge eCRF: 
• 
Location of bleed (indicate right or left groin) 
• 
Date and time of re-bleed 
• 
Complete adverse event form. 
7.5.  Follow-up at 30 (+/- 10) Days 
Subjects should have follow-up by office visit or telephone call 30 ± 10 days following their index 
procedure.  The subject should be queried regarding any complications they experienced after 
hospital discharge and the status of the access site wounds should be should be assessed by 
questioning and/or exam.  All subjects will be asked about any lower extremity nerve complaints 
in both lower limbs (i.e., symptoms, severity) that were not existing prior to the index procedure.  
In addition, the patient record will be reviewed regarding prescription of post-discharge pain 
medications  related to their recovery.These data will be captured in the Case Report Forms, as 
applicable. 
7.6. Study Exit 
Once the subject has completed the follow-up contact or has withdrawn, they should be exited 
from the study provided they do not have any closure-related conditions that require continued 
follow-up.  The date of exit and subject status should be recorded on the Study Exit CRF. 
8. Assessment of Effectiveness and Safety 
8.1. Primary Effectiveness Endpoint 
Procedure Success, Final hemostasis at all venous access sites and freedom from major venous 
access site closure-related complications through 30 days follow up. 
(Per-patient analysis, pooled across all study groups). 

 
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8.2. Secondary Effectiveness Endpoints 
Study Group Success (defined for each study group) 
o No Urinary Catheter: No peri-procedural urinary catheter insertion required through 
successful Ambulation. (Per-patient analysis) 
o No Protamine: No delay in Ambulation due to access site bleeding in subjects who 
receive heparin but are not reversed with protamine  
(Per-patient analysis)   
o Same Calendar Day  Discharge: Discharge within the same calendar day from the start of 
the procedure without the need for re-hospitalization within 72 hours of hospital 
discharge due to access site complications. 
(Per-patient analysis)   
Device Success, defined as the ability to deploy the delivery system, deliver the collagen, and 
achieve hemostasis with the Mid-Bore VVCS.  
(Per-access site analysis).  
 
8.3. Primary Safety Endpoint 
On a per-limb basis, the rate of combined major venous access site closure-related 
complications through 30 days post-procedure +/- 10 days, attributed directly to the closure 
method (i.e., “device-related” with no other likely attributable cause): 
• Access site-related bleeding requiring transfusion; 
• Vascular injury requiring surgical repair;  
• Access site-related infection confirmed by culture and sensitivity, requiring 
intravenous antibiotics and/or extended hospitalization; 
• New onset permanent access site-related nerve injury (i.e., persisting for > 30 days);  
• New onset access site-related nerve injury in the ipsilateral lower extremity requiring 
surgical repair; 
• Pulmonary embolism requiring surgical or endovascular intervention and/or resulting 
in death, to be confirmed by CT pulmonary angiography, lung ventilation/perfusion 
scan (VQ scan) or autopsy;  
Pulmonary embolism NOT requiring surgical or endovascular intervention and/or 
NOT resulting in death, to be confirmed by CT pulmonary angiography or lung 
ventilation/perfusion scan (VQ scan). 
8.4. Secondary Safety Endpoint 
On a per-limb basis, the rate of combined minor venous access site closure-related 
complications through 30 days post-procedure +/- 10 days, attributed directly to the closure 
method (i.e., “device-related” with no other likely attributable cause): 
• 
Access site-related bleeding requiring greater than 30 minutes of continual manual 
compression to achieve initial venous hemostasis; 
• 
Access site-related hematoma > 6 cm documented by ultrasound; 
• 
Late access site-related bleeding (following hospital discharge); 
• 
Ipsilateral deep vein thrombosis, confirmed by ultrasound/imaging; 

 
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• 
Localized access site infection confirmed by culture and sensitivity, treated with 
intramuscular or oral antibiotics; 
• 
Arteriovenous fistula requiring treatment;  
• 
Arteriovenous fistula not requiring treatment; 
• 
Pseudoaneurysm requiring thrombin injection, fibrin adhesive injection or 
ultrasound-guided compression; 
• 
Pseudoaneurysm not requiring treatment. 
• 
Access site-related vessel laceration 
• 
Access site-related wound dehiscence 
• 
Transient access site-related nerve injury 
9. Statistical Considerations 
9.1.  Analysis Populations and Data Handling Conventions   
 Effectiveness 
All subjects will be subject to all performance analyses and analyzed, regardless of actual 
treatment deviations. 
 Safety 
All subjects who receive any portion of the Cardiva VVCS device treatment will be included in 
the analysis.  
 Missing Data 
All efforts will be made to eliminate missing data for the primary effectiveness endpoint of 
procedure success and the primary safety endpoint of major access site closure-related 
complications.  However, should missing data be non-trivial, the primary analyses will be based 
on complete cases with data and sensitivity analyses will be performed to assess robustness of 
the primary results.  Multiple imputations strategy such as assuming missing at random and 
control based imputation will be employed for the primary effectiveness endpoint; worst case, 
best case and tipping point analyses will be performed for primary safety endpoint.  Missing 
data for secondary endpoints will not be imputed by any method.  
9.2. Statistical Analysis Plan  
 Baseline Subject Characteristics  
Subject demographics, baseline characteristics and medical history will be summarized 
descriptively both combined and by study group. Mean, standard deviation, median, minimum, 
and maximum will be reported for continuous variables. Frequencies and proportions will be 
reported for categorical variables. 
 Effectiveness 
Primary Effectiveness Analysis 

 
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The primary effectiveness analysis will be based on the procedure success rate of all subjects 
as defined in Section 8.1.   
Secondary Effectiveness Analysis 
The secondary effectiveness analysis will be based on the device success rate of all access sites 
and the study group success for each study group, as defined in Section 8.2.   
Effectiveness Endpoint Confidence Intervals 
The 95% confidence intervals for both primary and secondary effectiveness endpoints will be 
calculated using an exact binomial confidence interval. 
 
 Safety 
Primary Safety Analysis 
The primary safety analysis will be based on the 30-day limb incidence rate of combined major 
access site closure-related complications (see 8.3).  Both the combined rate and individual 
complication incidence rates will be reported.  
Secondary Safety Analysis 
The combined incidence rate and individual complication incidence rates will also be reported 
for minor access site closure-related complications (see 8.4).   
Additionally, all reported adverse events will be summarized by treatment regardless of 
relationship to access site closure.   
Safety Endpoint Confidence Intervals 
The 95% confidence intervals for both primary and secondary safety endpoints will be 
calculated using an exact binomial confidence interval. 
 
9.3. Sample Size Justification 
A sample size of 300 subjects is estimated based on expected enrollment during a 6-month period 
for 5 participating sites.  
10. Data Management – Data Collection and Processing 
Standardized eCRFs will be utilized by all participating sites, refer to the Manual of Operations for 
specifications and instructions. Investigators are responsible for the accurate completion and 
timely submission of the data collected during the trial.  All data from the trial will be entered into 
eCRFs via a secure, web-based system with password protection.  Incoming data will be 
automatically reviewed to identify inconsistent or missing data and any adverse events.  Any data 
issues are to be promptly addressed with the Investigator by the CRO.  Quality assurance 
procedures will be established to ensure that complete, accurate and timely data are submitted, 
that protocol requirements are followed, and that complications, adverse events and adverse 

 
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device effects are correctly reported and investigated, as appropriate.  Investigators are to 
maintain all source documents as required by the protocol, including laboratory results, 
supporting medical records, and signed Informed Consent forms.  The source documents will be 
used during the regular monitoring visits to verify information from the database against data 
contained on the completed eCRFs.  
The Principal Investigator must maintain detailed records on all subjects who sign the Informed 
Consent and begin the pre-procedure evaluation.  Data for enrolled subjects will be entered into 
eCRFs provided by the Sponsor.  All data should be entered completely, promptly and legibly.  For 
source documents, corrections should be made in a manner that does not obscure or eliminate 
the original error, by striking through the original data with one line, and initialing and dating the 
change, along with the reason for the change (if not obvious).   
Study Exit eCRFs are completed for all enrolled subjects, regardless of whether they completed all 
study requirements (e.g., subject discontinuation, trial termination). 
11. Monitoring Procedures 
11.1. Monitoring  
Monitoring visits to the clinical sites will be made periodically during the study, to ensure that all 
aspects of the current, approved protocol/amendment(s) are followed. Original source 
documents will be reviewed for verification of data in the electronic database. The 
Investigator/institution guarantees direct access to original source documents by Cardiva 
Medical, Inc. personnel, their designees, and appropriate regulatory authorities. In the event 
that the original medical records for adverse events cannot be obtained for a patient that is 
seen by a non-study physician at a non-study institution, photocopies of the original source 
documents must be made available for review. 
It is important that the Investigator and relevant study personnel are available during the 
monitoring visits and that sufficient time is devoted to the process. 
Phone contacts and site visits will be conducted to ensure that the protocol is being followed 
and that any protocol deviations are properly documented.  Clinical monitoring will include a 
verification that Informed Consent was properly obtained for all enrolled trial participants, a 
review of clinical records for accuracy and completeness, resolution of missing or inconsistent 
results and a review of source documents.  The Monitor will verify that the Case Report Forms 
(eCRFs) are in agreement with the source documentation and other records.  The Investigator 
will make available to the clinical monitor for review all Informed Consent documents, Internet 
access to completed eCRFs, source documentation, original laboratory data and other relevant 
records for all enrolled subjects at the site.  It is important that the Investigator and other 
relevant site personnel are available for consultation with the Monitors during the monitoring 
visits and that sufficient time is devoted at the site to the monitoring process. 

 
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Additionally, telephone and/or e-mail contact will be conducted on a regular basis with the 
Investigator and the site staff to ensure that the protocol is being followed and to address any 
issues that may occur during the course of the study. In some cases, remote monitoring and 
data cleaning may be performed. 
If a deficiency is noted during an on-site visit (or at any other time during the course of the trial), 
the Monitor is required to discuss the situation with the Investigator and the Sponsor (if 
required) to secure compliance. 
11.2. Investigational Device Distribution and Accountability 
 Investigational Device Distribution 
Cardiva Medical will provide and control the distribution of the investigational devices.  Each 
investigational site will be responsible for ordering the investigational devices for the study.  
The Investigator is responsible for ensuring that the devices are ordered for shipment to arrive 
at the hospital before the procedure date.  
Devices will be shipped with an Investigational Device Shipment Record.  This form is to be 
used by Cardiva Medical and the investigational site to record any shipments of the 
investigational device.  A copy is to be retained by the shipper and the recipient. 
Sites will be responsible for payment of the investigational devices and will coordinate with 
Cardiva Medical to secure shipping and payment arrangements prior to shipment. 
 Device Accountability 
The Investigator shall maintain adequate records of the receipt and disposition of all 
investigational devices.  The Investigator is responsible for ensuring that the investigational 
devices are used only under the Investigator’s supervision and are only used according to this 
protocol and any approved amendments.  The Investigator will not supply an investigational 
device to any person not authorized to participate in the trial. The Investigator shall document 
in the operative notes and eCRF’s the lot number of the devices used during a case.  In 
addition, the Investigator shall keep complete and accurate records of all devices used or 
unused that have been returned to Cardiva Medical in a Device Accountability Log provided by 
Cardiva Medical. 
 Return of Materials Upon Study Termination 
After the cases are completed, all unused devices must be accounted for and shipped back to 
Cardiva Medical.  Instructions for device return to Cardiva Medical will be reviewed at the site 
initiation visit. 
IMPORTANT:  Refer to the Manual of Operations for Device Return Instructions. 

 
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12. Quality Control and Quality Assurance 
12.1. Site Training 
To ensure accurate, complete, and reliable data, the Sponsor or its representatives will provide 
instructional material to the trial sites, as appropriate and will:  
• Instruct the Investigators and trial personnel on the protocol, the completion of the eCRFs, 
and trial procedures; 
• Communicate regularly with site personnel via mail, email, telephone, and/or fax; 
• Make periodic visits to the trial sites; 
• Conduct periodic remote data cleaning and correspondence. 
12.2. Investigator and Co-Investigator Training 
An Investigator is defined as the person responsible for the conduct of the clinical investigation 
at an investigational site. The Investigator is the responsible leader of the team and may be 
called the Principal Investigator.   
A Co-Investigator is defined as an individual member of the clinical investigation team 
designated and supervised by the Investigator at an investigational site who performs critical 
investigation-related procedures and/or makes important investigation-related observations, 
including enrollment of subjects and deployment of the study device.   
An Operator is defined as an individual member of the clinical investigation team who is 
qualified by training and experience (i.e., non-Investigator MD or certified vascular tech), and 
who is designated to deploy the study device in a study subject under the direction of, and the 
direct supervision of an Investigator or Co-Investigator.  
Site Investigators who have performed cases in the AMBULATE Randomized Study will not 
require additional training for the AMBULATE CAP Study. If a site adds a new Investigator, device 
training (IFU review, bench training, etc.) will be provided by a Sponsor-designated proctor prior 
to enrolling any subjects in the study. It is not anticipated that training cases (i.e., “Roll-ins”) will 
be required for this study. All Investigators will be trained to the CAP Study protocol and data 
collection requirements.  
New Investigators and Co-Investigators will be notified in writing when they have successfully 
completed the training requirements and are eligible to enroll subjects into the trial, and to 
deploy the study device without a Sponsor proctor. Operators will be notified in writing when 
they have successfully completed the enrollment requirements and are eligible to deploy the 
study device under the direct supervision of an Investigator/Co-Investigator in a consented, 
qualifying study patient without a Sponsor proctor. An Operator will not have authority to make 
any decisions about enrollment, but only to deploy the device as directed.  

 
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12.3. Audits and Inspections 
The Principal Investigator for the site will also allow representatives of the governing IRB, the 
United States Food and Drug Administration (FDA), and other applicable regulatory agencies to 
inspect all trial records, eCRFs, and corresponding portions of the subject’s office and/or 
hospital medical records at regular intervals throughout the study.  These inspections are for the 
purpose of verifying adherence to the protocol, completeness and exactness of the data being 
transcribed to the eCRF, and compliance with FDA or other regulatory agency regulations. 
The Principal Investigator for the site will inform the Sponsor or the Sponsor’s designee in 
advance if they are to be audited or inspected by any regulatory agencies.  The Sponsor or the 
Sponsor’s designee will also inform the site if they are made aware of a pending audit or 
inspection by a regulatory agency. 
13. Adverse Events 
General  
All adverse events (AE) and serious adverse events (SAE) will be monitored from the time of 
randomization through the 30 days +/- 10 days follow-up contact.  
An AE is defined as any undesirable clinical occurrence in a patient whether or not it is 
considered to be device related. In addition, the definition of AE applies to any event with an 
onset post study procedure or to any underlying diseases present at baseline, that exacerbate 
in severity post study procedure. Therefore, an underlying disease that was present at the time 
of enrollment is not reported as an AE, but any increase in the severity of the underlying 
disease is to be reported as an AE. This definition includes events occurring during the follow-
up period. 
All reported AEs must be recorded in the electronic database. A description of the event, 
including the start date, resolution date, action taken, and the outcome should be provided, 
along with the Investigator’s assessment of the relationship between the AE, the study 
treatment and the study procedure.  
 
 
The following definitions for rating severity of adverse events will be used: 
Mild: 
Awareness of signs or symptoms, but easily tolerated; are of minor irritant 
type; causing no loss of time from normal activities; symptoms would not 
require medication or a medical evaluation; signs or symptoms are transient. 
Moderate: 
Interferes with the subject’s usual activity and/or requires symptomatic 
treatment. 
Severe: 
Symptom(s) causing severe discomfort and significant impact of the subject’s 
usual activity and requires treatment. 
A serious adverse event (SAE) is defined as an event which leads to:   

 
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• 
Death due to any cause 
• 
Life-threatening condition 
• 
Results in persistent or significant disability/incapacity 
• 
Requires in-patient hospitalization or prolonged hospitalization 
• 
Results in congenital abnormality 
All SAE’s will be reported.  
Device-Related Adverse Event: an adverse event is considered to be device-related when, in the 
judgment of the Investigator, the clinical event has a reasonable time sequence associated with 
use of the investigational device and is unlikely to be attributed to concurrent disease or other 
procedures or medications.  It is reasonable to believe that the device directly caused or 
contributed to the adverse event.  
Procedure-Related Adverse Event: an adverse event is considered to be procedure-related when, 
in the judgment of the Investigator; it is reasonable to believe that the event is associated with the 
assigned study procedure and is not specific to the investigational device used.  Other products, 
surgical techniques, or medications required specifically for the procedure are likely to have 
contributed to the occurrence of the event. 
Concomitant Medication-Related Adverse Event: an adverse event is considered to be 
concomitant medication related when, in the judgment of the Investigator, it is reasonable to 
believe that the event is associated with concomitant medications used in conjunction with the 
investigational device and is not otherwise specific to the investigational device (e.g. bleeding 
associated with anticoagulation medication). 
Pre-Existing Condition-Related Adverse Event: an adverse event is considered to be related to a 
pre-existing condition when, in the judgment of the Investigator, it is reasonable to believe that 
the event is associated with the subject’s pre-existing condition and is not specific to the 
investigational device or procedure. Pre-existing conditions that are aggravated or become more 
severe during or after the procedure should be evaluated on a case-by-case basis to determine if 
the event may be more appropriately classified as device-related or procedure-related. 
Cardiva Medical, Inc., or its designee, in cooperation with the Investigator, will assess all adverse 
events considered to be device-related for potential reportability to the FDA and other regulatory 
authorities as an Unanticipated Adverse Device Effect (UADE).  
The Investigator should follow all unresolved serious adverse events until the events are resolved, 
the subject is lost to follow-up, the subject has withdrawn consent, or the adverse event is 
otherwise explained. 
Non-Events: For purposes of this study, the following events are not considered adverse events, 
because they are normally expected to occur in conjunction with catheter-based procedures / post-
procedure, or are associated with customary, standard care of subjects undergoing these procedures: 
• Early post-operative pain (within 48 hours post-index procedure) at the access site and/or 
related to position on procedure table and considered to be at least moderate in severity 

 
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• Post-anesthesia/conscious sedation emesis, nausea, or headache (within 24 hours post-index 
procedure) 
• Chest pain without associated ECG changes  
• Hematocrit decrease from baseline not associated with hemodynamic changes, remaining 
above 30% and not requiring transfusion 
• Electrolyte or fluid imbalance without clinical sequelae following procedure, even if requiring 
correction 
• Low grade temperature increase (≤38.3°C/≤101°F)  
• Abnormal cardiac rhythms that do not require treatment or intervention or are considered to 
be expected and not clinically significant based on the procedure performed 
• Systolic or diastolic blood pressure changes that do not require treatment or intervention 
• Any pre-planned surgical procedures 
This listing of events is intended to provide guidance to the investigational sites for purposes of adverse 
event reporting.  The Investigator at the investigational site should utilize his/her own clinical judgment 
in evaluating adverse experiences, and may decide that the above events should be reported as 
adverse events.   
13.1. Reporting of Serious and Non-Serious Adverse Events  
 General Reporting Requirements (Serious & Non-Serious Adverse Events) 
All serious and potentially device- and/or procedure-related adverse events must be recorded 
on the Adverse Event eCRF by the Investigator (or designee).  The report should include: 
severity, duration, action taken, treatment outcome and relationship of the adverse experience 
to the study device, procedure, concomitant medications, pre-existing condition, etc. (i.e., 
unrelated, related or relationship unknown).   
In the case of serious adverse events, procedure and/or device observations and malfunctions, 
medical record documentation (e.g. procedure notes, operative notes, discharge summary, 
relevant progress notes, imaging or lab studies) must be provided to Cardiva Medical or its 
designee.  
The following criteria must also be adhered to by the Investigator in the case of serious adverse 
events: 
• 
It is the responsibility of the Investigator to inform their IRB of serious adverse events as 
required by their IRB’s procedures and in conformance with FDA and local regulatory 
requirements. 
All serious device- and/or procedure-related adverse events must be reported by the 
Investigator (or designee) to the Sponsor within 24 hours of learning of the adverse event via 
eCRF. The Cardiva Medical contact information for questions is: 

 
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Sponsor: 
Cardiva Medical, Inc. 
2900 Lakeside Drive, Ste. 160 
Santa Clara, CA  95054 
Telephone:  408-470-7170 
Fax:  408-470-7134 
 
Contact: 
Marlys Chellew, BSN 
 
 
Clinical Consultant 
 
 
Mobile:  916-303-0879 
 
 
mchellew@chellewclinical.com 
13.2. Device Failures and Malfunctions 
All reported device malfunctions or failures of the Cardiva Mid-Bore VVSC are required to be 
documented in the eCRF.  In the event of a suspected observation or device problem, the 
investigational device shall be returned to the Sponsor for analysis.  Device failures and 
malfunctions should also be documented in the patient’s medical record if a related adverse 
event occurs. Instructions for returning the investigational device are included in the Manual of 
Operations.  
NOTE: Device failures or malfunctions are NOT to be reported as adverse events. However, if 
there is an adverse event that results from a device failure or malfunction, that specific event 
would be recorded in the usual way. See Manual of Procedures for specific reporting guidelines. 
14. Study Committee 
14.1. Data Safety Monitoring  
All reported major and minor access site-closure related endpoint complications and any access-
site closure related complications as reported by the Investigator will be submitted in a progress 
report to the FDA at 50% of planned enrollment.  
15. Ethical Considerations 
15.1. Trial Conduct & the Declaration of Helsinki 
The trial will be performed in accordance with the relevant parts of Title 21 CFR Parts 812, 50, 
54, 56; the ICH Guidelines for Good Clinical Practices (E6), and any regional and/or national 
regulations. 
15.2. Institutional Review Board/Ethics Committee 
The CAP Study is considered to be an amendment to the AMBULATE Randomized study, per IDE 
G170144, and will only utilize investigational sites that participated in the AMBULATE Study. A 
copy of the protocol, proposed Informed Consent form, other written patient information and 
any proposed advertising material must be submitted to the IRB for written approval. A copy of 
the written IRB approval of the protocol and Informed Consent form must be received by 

 
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Cardiva Medical, Inc. prior to recruitment of patients into the study and shipment of 
investigational product. 
The Investigator must submit and, where necessary, obtain approval from the IRB as well as the 
FDA and Sponsor, for all subsequent significant protocol amendments and significant changes to 
the Informed Consent form.  The Investigator should notify the IRB of deviations from the 
protocol or SAEs and UADEs occurring at the site and other SAE/UADE reports received from 
Cardiva Medical, Inc. in accordance with local procedures. 
The Investigator will be responsible for obtaining annual IRB approval and renewal throughout 
the duration of the study. Copies of the Investigator’s reports and the IRB continuance of 
approval must be sent to Cardiva Medical, Inc.  
15.3. Informed Consent Form 
Sample Informed Consent forms are provided for subjects in Attachment 2 for the Investigator 
to prepare for use at his/her site. The Sponsor will review each site’s redlines to the ICF and 
provide written approval prior to site submission of the documents to their respective IRBs. The 
reviewing IRB must then approve the ICF prior to use. If translations are required for specific 
populations, the Sponsor will provide certified translations for the site after IRB approval of the 
site template.  
The reviewing IRB, the FDA and the Sponsor must first approve the Informed Consent form that 
is used. The Informed Consent forms must be in accordance with the current guidelines as 
outlined by the Good Clinical Practices (GCP) guidelines and 21 CFR Part 50.  
Prior to participation in the clinical trial, each patient must give written Informed Consent after 
the context of the study has been fully explained to the patient in language that is easily 
understood by the patient. The patients must also be given the opportunity to ask questions and 
have those questions answered to their satisfaction. 
Written Informed Consent must be recorded appropriately by means of the patient’s dated 
signature on the ICF. The person administering the Informed Consent shall also sign and date 
the ICF. The patient shall receive a copy of the ICF, and the informed consent process shall be 
documented in each subject’s source record. 
15.4. Amending the Protocol 
An Investigator may not make protocol changes without prior approval by Cardiva Medical.  All 
significant protocol changes that may affect the following must be submitted and approved by 
the FDA before initiating the change: 
• 
validity of the data or information resulting from the completion of the approved protocol; 
• 
relationship of the likely subject risk to benefit relied upon to approve the protocol; 
• 
scientific soundness of the investigational plan, or; 

 
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• 
rights, safety, or welfare of the human subjects involved in the investigation. 
The change must be approved by the FDA and submitted and subsequently approved by the site 
IRB.  Cardiva Medical will submit a copy of the protocol amendment to all Investigators for their 
IRB’s to review and ensure the study continues to be conducted consistently across all sites.  The 
investigative sites must send Cardiva Medical a copy of the IRB approval letter for the protocol 
amendment. 
Cardiva Medical may make certain administrative changes to the protocol without prior 
approval of the FDA or IRB.  Cardiva Medical will notify all investigative sites of such changes to 
ensure the study continues to be conducted consistently across all sites.  The site IRB’s will be 
notified of these changes. 
15.5. Emergency Actions 
Cardiva Medical, Inc. accepts the right of the Investigator to deviate from the protocol in an 
emergency when necessary to safeguard the life or the physical well-being of a study patient. 
The Investigator must give notice of any emergency deviations and justification for the deviation 
to Cardiva Medical, Inc. and the IRB as quickly as possible after the episode, in any event no later 
than 24 hours after the emergency. 
15.6. Protocol Deviations 
A protocol deviation is defined as an event where the Clinical Investigator or site personnel did 
not conduct the study according to the protocol. 
Investigators shall be required to obtain prior approval from Cardiva Medical clinical study 
management before initiating deviations from the protocol, except where necessary to protect 
the life or physical well-being of a subject in an emergency.  Such approval shall be documented 
in writing and maintained in clinical study management and Investigator files.  Prior approval is 
generally not expected in situations where unforeseen circumstances are beyond the 
Investigator’s control, (e.g. subject was not available for scheduled follow-up contact, blood 
sample lost by laboratory, etc.); however, the event is still considered a deviation and will be 
reported via the appropriate CRF. 
Deviations must be reported to Cardiva Medical regardless of whether medically justifiable, pre-
approved by Cardiva Medical or taken to protect the subject in an emergency.  Subject specific 
deviations and non-subject specific deviations, (e.g. unauthorized use of an investigational 
device outside the study, unauthorized use of an investigational device by a physician who has 
not signed an Investigator agreement or not been trained in the use of the device, etc.), will be 
reported on the Protocol Deviation case report form. Investigators will also adhere to 
procedures for reporting study deviations to their IRB in accordance with their specific IRB 
reporting policies and procedures. 

 
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Regulations require that Investigators maintain accurate, complete and current records, 
including documents showing the dates of and reasons for each deviation from the protocol.  
For reporting purposes, Cardiva Medical classifies study deviations as major and minor: 
Major deviation:  Any deviation from subject inclusion and exclusion criteria, subject informed 
consent procedures or unauthorized device use. 
Minor deviation: Deviation from a protocol requirement such as incomplete/inadequate subject 
testing procedures, follow-ups performed outside specified time windows, etc. Minor Deviations 
that continue to occur at an investigational site may be classified as Major Deviations if 
corrective action is not taken to secure future compliance to the protocol. 
Major and/or recurring protocol deviations reported or identified by the monitor will be 
discussed with the investigative staff to identify root cause and corrective actions to be 
implemented to prevent recurrence. Investigators are expected to participate in this important 
activity in a serious and timely manner. 
15.7. Coverage of Expenses 
The treated subjects will not be reimbursed or compensated for participating in the trial. 
15.8. Confidentiality  
Confidentiality of subjects will be maintained throughout the trial.  A unique identification code 
will be assigned to each subject participating in this trial.  Any data that may be published in 
abstracts, scientific journals, or presented at medical meetings will reference a unique subject 
code and will not reveal the subject’s identity.  The Sponsor and their CRO representative will 
make every reasonable effort to protect the confidentiality of the subjects participating in the 
trial. 
16. Study Administration 
This AMBULATE Continued Access Protocol (CAP) Study is a continued access protocol under the 
AMBULATE IDE Study1 conducted per Clinical Investigation Protocol PTL 0508. Cardiva Medical, 
Inc. will make necessary efforts to ensure that this study is conducted in compliance with GCPs 
and all applicable regulatory requirements. 
16.1. Pre-Study Documentation Requirements 
Prior to shipment of investigational product, the following documents must be provided to 
Cardiva Medical, Inc.: 
• 
Signed and dated Investigator Agreement and Financial Disclosure Form 
• 
Fully executed Clinical Study Agreement and budget 
 
1 G170144 AMBULATE IDE 

 
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• 
Purchasing agreement for investigational devices 
• 
A copy of the written IRB approval of the protocol and Informed Consent Forms 
• 
A copy of the IRB-approved Informed Consent Forms  
• 
A copy of the curriculum vitae of the Principal Investigator. 
16.2. Source Documentation 
The Principal Investigator must maintain detailed source documents on all trial subjects who are 
enrolled in the trial or who undergo screening.  Source documents include subject medical 
records, hospital charts, clinic charts, Investigator’s subject trial files, as well as the results of 
diagnostic tests (e.g., laboratory tests). 
The following minimum information should be recorded in the subject’s source records: 
• 
The date the subject entered the study and the subject ID number 
• 
The study name 
• 
The date that informed consent was obtained 
• 
Evidence that the subject meets trial eligibility requirements (e.g., medical history, trial 
procedures and/or evaluations) 
• 
The dates of all trial related subject visits 
• 
Evidence that required procedures and/or evaluations were completed 
• 
Documentation of specific investigational devices used, if any 
• 
Occurrence and status of any Adverse Events 
• 
The date the subject exited the study, and a notation as to whether the subject completed 
the study or was discontinued, including the reason for discontinuation. 
16.3. Record Retention & Custody 
The Investigator will maintain all essential trial documents and source documentation, in 
original format, that support the data collected on the study patients in compliance with the 
ICH/GCP guidelines. Documents must be retained for at least 5 years after the last approval of 
marketing application or until at least 5 years have elapsed since the formal discontinuation of 
the clinical investigation of the product. These documents will be retained for a longer period of 
time by agreement with Cardiva Medical, Inc. or in compliance with other regulatory 
requirements. When these documents no longer need to be maintained, it is Cardiva Medical’s 
responsibility to inform the Investigator. The Investigator will take measures to ensure that 
these essential documents are not accidentally damaged or destroyed. If for any reason the 
Investigator withdraws responsibility for maintaining these essential documents, custody must 
be transferred to an individual who will assume responsibility. Cardiva Medical, Inc. must 
receive written notification of this custodial change.  

 
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16.4. Criteria for Terminating Study 
Cardiva Medical, Inc. reserves the right to terminate the study but intends only to exercise this 
right for valid scientific or administrative reasons and reasons related to protection of patients. 
Investigators and associated IRBs will be notified in writing in the event of termination. 
Possible reasons for study termination include: 
• 
The discovery of an unexpected, significant, or unacceptable risk to the patients enrolled in 
the study. 
• 
A decision on the part of Cardiva Medical, Inc. to suspend or discontinue development of 
the device. 
• 
Market approval of the study device. 
16.5. Criteria for Suspending/Terminating a Study Center 
Cardiva Medical, Inc. reserves the right to stop the enrollment of patients at a study center at 
any time after the study initiation visit if no patients have been enrolled or if the center has 
multiple or severe protocol violations without justification or fails to follow remedial actions. 
Possible reasons for suspending/terminating a study center include: 
• 
Repeated failure to complete electronic case report forms prior to scheduled monitoring 
visits. 
• 
No or slow enrollment. 
• 
Multiple or major protocol deviations without justification, or failure to follow remedial 
actions 
• 
Failure to obtain written Informed Consent prior to enrollment 
• 
Failure to report serious device-related AEs and/or UADEs to Cardiva Medical, Inc. within 
24 hours of knowledge 
• 
Loss of (or unaccounted for) investigational product inventory. 
16.6. Investigator Responsibilities 
• 
Agree to sign and adhere to the Investigator Agreement 
• 
Be willing to provide required assessments for analysis 
• 
Be willing to perform and be capable of performing treatment procedures as outlined in this 
protocol and to delegate study responsibilities only to qualified personnel 
• 
Comply with all required elements of this protocol and supply material suitable for 
quantitative analysis 
• 
Agree to obtain written Informed Consent before any study specific procedures are 
performed  
• 
Complete all electronic data modules prior to scheduled monitoring visits 

 
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• 
Be willing to change hospital routine if required by protocol, as long as patient safety and 
well-being is not compromised 
A full list of Investigator responsibilities is provided in Attachment 1. 
17. Publication Policy 
The existence of this clinical trial is confidential, and it should not be discussed with persons 
outside of the trial.  Additionally, the information in this document and regarding this trial 
contains trade secrets and commercially sensitive information that is confidential and may not be 
disclosed unless such disclosure is required by regional or national law or regulations.  Subject to 
the foregoing, this information may be disclosed only to those persons involved in the trial who 
have a need to know, but all such persons must be instructed not to further disseminate this 
information to others.  These restrictions of disclosure will apply equally to all future information 
provided that is indicated as confidential. 
The data generated by this clinical trial are the property of the Sponsor, Cardiva Medical, Inc., and 
should not be disclosed without their prior written permission.  These data may be used by the 
Sponsor now and in the future for presentation or publication at Sponsor’s discretion or for 
submission to governmental regulatory agencies.  The Principal Investigators may publish or 
present the trial results with prior consent of the Sponsor, but will not disclose confidential 
information.  Prior to submission by a Principal Investigator for publication or presentation, the 
Sponsor will be provided with the opportunity to review the submission for confidential 
information and accuracy. The Sponsor will have the opportunity to a) approve the publication; b) 
require the removal of any Confidential Information (other than Study Data); and /or c) delay the 
proposed Publication for an additional ninety (90) days to enable Sponsor to seek patent 
protection. 
The study will be posted on ClinicalTrials.gov prior to enrollment of the first subject, as required by 
regulation. 
18. Regulatory Considerations 
18.1. Role of Cardiva Medical 
As the Sponsor of this clinical study, Cardiva Medical has the overall responsibility for the conduct 
of the study, including assurance that the study meets the regulatory requirements of the Food 
and Drug Administration (FDA).  In this study, Cardiva Medical will have certain direct 
responsibilities and will delegate other responsibilities to Consultants.  Together, both Cardiva 
Medical and its Consultants will ensure adherence to the Sponsor’s general duties (21 CFR 
812.40), selection of Investigators (21 CFR 812.43), monitoring (21 CFR 812.46), supplemental 
applications (21 CFR 812.35 (a) and (b)), maintaining records (21 CFR 812.140 (b)), and submitting 
reports (21 CFR 812.150 (b)). 

 
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18.2. General Duties [21 CFR 812. 40] 
The Sponsor’s general duties consist of submitting the IDE application to FDA, obtaining FDA and 
IRB approvals prior to shipping the devices, selecting qualified Investigators and shipping devices 
only to those qualified Investigators. As the Sponsor, Cardiva Medical is also required to obtain 
signed study agreements, to provide the Investigators with the information necessary to 
conduct the study and adequate on-site training to conduct the trial, to ensure proper clinical 
site monitoring, and to provide the required reports to the Investigators, IRB’s and FDA.  
Cardiva Medical will be responsible for providing quality data that satisfies federal regulations 
and informing of serious unanticipated adverse events and deviations from the protocol.  
Written progress reports and a final report will be prepared and will coordinate with the 
Ultrasound Core Laboratory. 
18.3. Monitoring [21 CFR 812. 46] 
The Sponsor and/or designee will conduct investigational site monitoring to ensure that all 
Investigators are in compliance with the protocol and the Investigators’ agreements. The 
Sponsor and/or designee will monitor the sites to ensure that the completed Case Report Forms 
match the medical records, and resolve any differences. The Sponsor will retain the right to 
remove either the Investigator or the investigational site from the study. 
The Sponsor will review significant new information, including unanticipated serious adverse 
events and ensure that such information is provided to the FDA, the Investigators and to all 
reviewing IRB’s. 
18.4. Supplemental Applications [21 CFR 812. 335 (A) and (B)] 
As appropriate, the Sponsor will submit changes in the Investigational Plan to the FDA and 
Investigators to obtain IRB re-approval. 
18.5. Maintaining Records [21 CFR 812. 140 (B)] 
The Sponsor will maintain copies of correspondence, data, shipment of devices, serious adverse 
device effects and other records related to the clinical trial.  The Sponsor will maintain records 
related to the signed Investigator Agreements.   
18.6. Submitting Reports [21 CFR 812. 150 (B)] 
The Sponsor will submit the required FDA reports identified in this section of the regulation.  
This includes unanticipated serious adverse device effects, withdrawal of IRB or FDA approval, 
current 6-month Investigators list, annual progress reports, recall information, final reports, 
Investigators that use the device without obtaining informed consent, and significant risk device 
determinations. 

 
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18.7. Site Record Retention Policy [21 CFR 812. 140 (D)] 
The Sponsor, Ultrasound Core Lab, and clinical sites will maintain all records pertaining to this 
study for a period of five years following: the date on which the investigation is terminated or 
completed, or the date that the records are no longer required for purposes of supporting a pre-
market approval application. Record retention dates will be provided to all concerned by the 
Sponsor. 
18.8. Informed Consent & Institutional Review Board (IRB) [21 CFR Parts 50 & 56] 
All subjects must provide written informed consent in accordance with the local clinical site’s 
IRB.  A copy of the consent form from each center must be forwarded to the Sponsor for review 
and approval prior to submitting it to the IRB.  Each site must provide the Sponsor with a copy of 
the clinical site’s IRB approval letter and the informed consent.  Yearly approvals for the 
continuation of the trial at each clinical site must also be forwarded to the Sponsor. 
All Protected Health Information (PHI) to be collected in the study will be described in the 
informed consent form, and all study data will be managed in accordance with the Privacy Law 
(HIPAA). 
 
 

 
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19. Abbreviations and Definitions 
19.1. Abbreviations 
 
ACT 
Activated clotting time 
AE 
Adverse Event 
AV 
Arteriovenous 
CFR 
Code of Federal Regulations 
eCRF 
Electronic Case Report Form 
CV 
Curriculum Vitae 
DE 
Discharge Eligibility 
FDA 
Food and Drug Administration 
Fr 
French 
Hgb 
Hemoglobin 
Hct 
Hematocrit 
IDE 
Investigational Device Exemption 
IFU 
Instructions for Use 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
LMWH 
Low molecular weight heparin 
MC 
Manual Compression 
PE 
Pulmonary embolism 
SAE 
Serious Adverse Event 
UADE 
Unanticipated Adverse Device Event 
 
 

 
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19.2. Definitions 
ACCESS SITE-RELATED HEMATOMA > 6 CM (minor safety endpoint) 
A localized collection of extravasated blood in subcutaneous tissue at the access site measuring > 6 cm at its widest 
point on visual inspection or palpation. 
ACCESS SITE-RELATED BLEEDING REQUIRING TRANSFUSION (major safety endpoint) 
Bleeding originating from the venous access site(s), which has occurred to the degree that transfusion of blood 
products is necessary to maintain hemodynamic stability. 
ACCESS SITE-RELATED BLEEDING REQUIRING > 30 MINUTES OF CONTINUAL MANUAL COMPRESSION TO ACHIEVE 
INITIAL VENOUS HEMOSTASIS (minor safety endpoint) 
Bleeding from the venous access site(s) requiring greater than 30 consecutive minutes of manual compression to 
achieve venous initial hemostasis. 
ACCESS SITE-RELATED INFECTION CONFIRMED BY CULTURE AND SENSITIVITY: REQUIRING INTRAVENOUS 
ANTIBIOTICS AND/OR PROLONGED HOSPITALIZATION (major safety endpoint) 
Must meet at least one of the following criteria related to the venous access site(s): 1) positive wound culture 
requiring treatment with intravenous antibiotics; and/or 2) prolonged hospital discharge time directly related to 
complications of access site infection.  Does not include administration of prophylactic antibiotic regimens. 
ACCESS SITE-RELATED INFECTION CONFIRMED BY CULTURE AND SENSITIVITY: LOCALIZED AND REQUIRING 
INTRAMUSCULAR OR ORAL ANTIBIOTICS (minor safety endpoint) 
Must meet BOTH of the following criteria related to the venous access site(s): 1) positive wound culture requiring 
treatment with intramuscular or oral antibiotics; and 2) no prolongation of hospital discharge time directly related 
to complications of access site infection.  Does not include administration of prophylactic antibiotic regimens. 
ACCESS SITE-RELATED NERVE INJURY IN THE IPSILATERAL LIMB – NEW ONSET AND REQUIRING SURGICAL REPAIR 
(major safety endpoint) 
New onset access site closure-related nerve injury that requires surgical intervention to mitigate symptoms or 
prevent permanent nerve damage. 
ACCESS SITE-RELATED NERVE INJURY – NEW ONSET AND PERMANENT (major safety endpoint) 
New onset access site closure-related nerve injury that persists for > 30 days and is deemed to be clinically 
significant by the Investigator.  
ACCESS SITE-RELATED NERVE INJURY – TRANSIENT (minor safety endpoint) 
New onset access site closure-related nerve injury that persists for < 30 days and is deemed to be clinically 
significant by the Investigator. 
ACCESS SITE-RELATED VESSEL LACERATION (minor safety endpoint) 
An injury to the venous or arterial wall in which the tissue is torn or cut.  
ACCESS SITE-RELATED WOUND DEHISCENCE (minor safety endpoint) 
A surgical complication in which the wound ruptures along a surgical incision. 
ADVERSE EVENT SEVERITY RATING 
Mild: 
Awareness of signs or symptoms, but easily tolerated; are of minor irritant type; 
causing no loss of time from normal activities; symptoms would not require 

 
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medication or a medical evaluation; signs or symptoms are transient. 
Moderate: 
Interferes with the subject’s usual activity and/or requires symptomatic treatment. 
Severe: 
Symptom(s) causing severe discomfort and significant impact of the subject’s usual 
activity and requires treatment. 
ALLERGIC RESPONSE  
A state of abnormal and individual hypersensitivity acquired through exposure to a particular allergen. 
APPROVAL (IN RELATION TO INSTITUTIONAL REVIEW BOARDS (IRBs)) 
The affirmative decision of the IRB that the clinical investigation has been reviewed and may be conducted at the 
institutional site within the constraints set forth by the IRB, the institution, Good Clinical Practice (GCP), and the 
applicable regulatory requirements. 
ARTERIOVENOUS (AV) FISTULA NOT REQUIRING TREATMENT (minor safety endpoint) 
A connection between the access vein and the adjacent artery that is demonstrated by arteriography or 
ultrasound, most often characterized by a continuous bruit that is mild to moderate in nature and does not require 
an intervention in the opinion of the Investigator. 
ARTERIOVENOUS (AV) FISTULA REQUIRING TREATMENT (minor safety endpoint) 
A connection between the access artery and the adjacent vein that is demonstrated by arteriography or 
ultrasound, most often characterized by a continuous bruit that is severe in nature and requires an interventional 
procedure to mitigate further injury. 
CHADS-2 SCORE 
Clinical prediction rules for estimating the risk of stroke in patients with non-rheumatic atrial fibrillation (AF). Such 
a score is used to determine whether or not treatment is required with anti-coagulation or anti-platelet therapy, 
since AF can cause stasis of blood in the upper heart chambers, leading to the formation of a mural thrombus that 
can dislodge into the blood flow, reach the brain, cut off supply to the brain, and cause a stroke. A high score 
corresponds to a greater risk of stroke, while a low score corresponds to a lower risk of stroke. 
 Condition 
Points 
C 
Congestive Heart Failure 
1 
H 
 Hypertension, BP consistently above 140/90 mmHg (or on 
medication) 
1 
A 
 Age > 75 years 
1 
D 
 Diabetes mellitus 
1 
S2 
 Prior Stroke / TIA or Thromboembolism 
2 
CO-INVESTIGATOR  
Any individual member of the clinical investigation team designated and supervised by the Investigator at an 
investigational site who performs critical investigation-related procedures and/or makes important investigation-
related observations, including enrollment of subjects.  See also Investigator and Operator.  
CONFIDENTIALITY  

 
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Prevention of disclosure, to other than authorized individuals, of a Sponsor's proprietary information or of a 
subject's identity / Protected Health Information (PHI) in compliance with the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA). 
DEVICE FAILURE / MALFUNCTION 
The device does not perform in accordance with the IFU. 
DEVICE SUCCESS  
Defined as the ability to deploy the delivery system, deliver the collagen, and achieve hemostasis with the Cardiva 
Venous Vascular Closure System. 
ELECTRONIC CASE REPORT FORM (eCRF) 
An electronic document designed to record all of the protocol-required information to be reported to the Sponsor 
on each subject. 
EMBOLISM 
The sudden blocking of an artery or vein by a clot or other material that has been brought to its site of lodgment 
by the blood current (embolus).  Potential sources of emboli include thrombus, air, calcific debris, device 
components, or other material.  
HEMATOMA 
A localized collection of extravasated blood in subcutaneous tissue, usually clotted.  Measure the widest portion of 
the hematoma in centimeters. 
HEMOSTASIS - VENOUS 
Cessation of common femoral venous bleeding from the puncture site (excluding cutaneous or subcutaneous 
oozing). 
INFLAMMATORY RESPONSE 
A localized protective response elicited by injury or destruction of tissues, not necessarily synonymous with 
infection. 
INFORMED CONSENT 
A process by which a subject voluntarily confirms in writing his or her willingness to participate in a particular 
investigation, after having been informed of all aspects of the investigation that are relevant to the subject's 
decision to participate.  Informed consent is documented by means of a written, signed, and dated Informed 
Consent form.  
INTERNATIONAL NORMALIZED RATIO (INR) 
A comparative rating of Prothrombin time (PT) ratios.  Used to measure coumadin efficacy in subjects. 
INTIMAL TEAR / DISSECTION 
Disruption of a vessel wall resulting in splitting and separation of the intimal (subintimal) layers. 
INVESTIGATIONAL SITE 
The location(s) where investigation-related activities are actually conducted.  
INVESTIGATOR 

 
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The person responsible for the conduct of the clinical investigation at an investigational site.  If an investigation is 
conducted by a team of individuals at an investigational site, the Investigator is the responsible leader of the team 
and may be called the Principal Investigator.  See also Co-Investigator and Operator.  
IPSILATERAL 
Situated on or affecting the same side (e.g., same side of the body as the access site). 
IPSILATERAL DEEP VEIN THROMBOSIS (minor safety endpoint) 
Presence of a thrombus in the peripheral venous system of the ipsilateral limb.  May be a complication of phlebitis 
or may result from injury to a vein or from prolonged bed rest. Symptoms include a feeling of heaviness, pain, 
warmth, or swelling in the affected part. 
LATE ACCESS SITE-RELATED BLEEDING (i.e., following hospital discharge) (minor safety endpoint) 
Active re-bleeding from the venous access site(s) following hospital discharge. See “Oozing From the Access Site” 
and “Re-bleeding at Access Site” definitions to differentiate between venous and tissue tract bleeding. 
LIGHT PRESSURE METHODS 
Light, non-occlusive pressure to the venotomy site applied to stabilize non-venous bleeding at the access site (i.e., 
light digital pressure, mechanical compression devices used at low pressure to manage tissue tract ooze).  
MANUAL COMPRESSION  
Direct digital non-occlusive pressure to the venotomy site applied to achieve hemostasis.  Note: Mechanical 
compression devices, sandbags and other methods are to be used only following the achievement of hemostasis 
for management of non-venous oozing/bleeding.   
LAST PROCEDURAL DEVICE 
Refers to the final device removed from procedural sheaths used in the index procedure, e.g. the A-Fib procedure 
prior to any sheath exchanges e.g. from long to short sheaths. 
LOWER EXTREMITY ISCHEMIA  
New (acute) onset of compromised peripheral blood flow, potentially causing a threat to the viability of the limb 
and requiring surgical or percutaneous intervention.  This compromised blood flow is documented by subject 
symptoms, physical exam and/or a decreased or absent blood flow on lower extremity angiogram. 
OOZING FROM THE ACCESS SITE 
Minimal bleeding of a cutaneous or subcutaneous origin characterized by the absence of accumulated blood under 
the skin (e.g., hematoma) and controlled with the application of light compression methods (sand bags, pressure 
dressings, and light manual pressure).  Note:  the occurrence of oozing will not be incorporated into the “time to 
hemostasis” measurement. 
PERFORATION OF VESSEL WALL 
A hole or break in the venous or arterial wall (e.g., from insertion of a percutaneous device). 
PROCEDURE SUCCESS  
Defined as attainment of Final hemostasis at all venous access sites and freedom from major venous access site 
closure related complications through 30 days follow up. 
PSEUDOANEURYSM AT ACCESS SITE WHICH MAY OR MAY NOT REQUIRE TREATMENT (minor safety endpoint) 

 
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A blood vessel abnormality resembling an aneurysm (localized abnormal dilatation of a blood vessel) but consisting 
of a collection of blood with persistent flow outside an artery, contained by surrounding tissue and due to a leaking 
hole through all layers of the arterial wall.  The leaking hole is due to injury of (e.g., rupture of or trauma to) the 
arterial wall.  The pseudoaneurysm is usually identified by angiography or ultrasound, and may or may not require 
treatment (e.g., thrombin injection or fibrin adhesive injection).  
PULMONARY EMBOLISM REQUIRING SURGICAL OR ENDOVASCULAR INTERVENTION AND/OR RESULTING IN 
DEATH (major safety endpoint) 
A blockage of an artery in the lungs by a substance that has traveled from elsewhere in the body through the 
bloodstream (i.e., embolism) that requires surgical or endovascular intervention and/or results in death, to be 
confirmed by CT pulmonary angiography, lung ventilation/perfusion scan (VQ scan) or autopsy.  
PULMONARY EMBOLISM NOT REQUIRING SURGICAL OR ENDOVASCULAR INTERVENTION AND/OR NOT 
RESULTING IN DEATH (major safety endpoint) 
A blockage of an artery in the lungs by a substance that has traveled from elsewhere in the body through the 
bloodstream (i.e., embolism) that does not require surgical or endovascular intervention and/or does not result in 
death, to be confirmed by CT pulmonary angiography, lung ventilation/perfusion scan (VQ scan) or autopsy.  
PUNCTURE SITE PAIN 
Local discomfort at the venous access site, which may range from mild to severe. 
RE-BLEEDING AT ACCESS SITE 
Active venous bleeding from the puncture site occurring after initial hemostasis has been confirmed and requiring 
manual compression to re-achieve hemostasis. 
RETROPERITONEAL BLEEDING 
Bleeding from an injured vessel, with deposition of blood into the retroperitoneal space (between the peritoneum 
and the posterior abdominal wall). 
SERIOUS ADVERSE EVENT (SAE)  
Any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or 
prolongation of existing hospitalization, or results in persistent or significant disability/incapacity, or is a congenital 
anomaly/birth defect.  
SUB-INVESTIGATOR / CO-INVESTIGATOR 
Any individual member of the clinical investigation team designated and supervised by the Investigator at an 
investigational site who performs critical investigation-related procedures and/or makes important investigation-
related observations.  See also Investigator.  
SUBJECT 
An individual who participates in a clinical investigation. 
THROMBUS FORMATION 
Blood clot formation. 
UNANTICIPATED ADVERSE DEVICE EFFECTS (UADE) 
Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated 
with the study device, if that effect, problem or death was not previously identified in nature, severity, or degree of 

 
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incidence in the Investigational Plan or any other unanticipated serious problem associated with a device that 
relates to the rights, safety, or welfare of subjects. 
VASCULAR INJURY REQUIRING SURGICAL REPAIR (major safety endpoint) 
Access site closure-related injury to the venous wall or adjunct arterial vessel wall resulting in persistent bleeding 
and requiring surgical repair.  
VASOVAGAL EPISODE 
A transient vascular and neurogenic reaction marked by pallor, nausea, and/or sweating symptoms, bradycardia 
and rapid fall in blood pressure, which may lead to a loss of consciousness and ECG changes.  
VASOSPASM 
The sudden, but transitory constriction of a blood vessel, potentially causing discomfort and limitation of distal 
blood flow. 
VESSEL OCCLUSION (ARTERIAL OR VENOUS) 
Total obstruction of the vein or artery by thrombus or other emboli requiring surgical or interventional repair, 
thrombolysis or percutaneous thrombectomy. 
VESSEL THROMBUS (ARTERIAL / VENOUS) 
Formation or development of a blood clot or thrombus in the arterial or venous system of the ipsilateral distal 
extremity. 
 
19.3. Bibliography 
 
1. Dou, E., Winokur, R.S., Sista, A.K. Venous access site closures using the VASCADE vascular closure 
system. J. Vasc. Interv. Radiol. 2016;27:1885–1888. 
2. Srivatsa, S.S., Srivatsa, A., Spangler, T.A. Mynx vascular closure device achieves reliable closure and 
hemostasis of percutaneous transfemoral venous access in a porcine vascular model. J Invasive 
Cardiol. 2015 Feb; 27(2):121-7. 
 
 
 

 
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20. Attachment 1: Investigator Responsibilities, Records and Reports 
20.1. Investigator Responsibilities 
The Investigator is responsible for ensuring that this trial is conducted according to this protocol 
and that signed Informed Consent is obtained from each subject prior to their inclusion in this 
trial. 
It is the Investigator’s responsibility to ensure that all staff assisting with this trial have the 
appropriate qualifications and are fully instructed on the trial procedures and respect subject 
confidentiality, as specified in the Investigator Agreement with the Sponsor. 
The Investigator is responsible for ensuring that the conduct of the trial conforms to the IRB/EC 
requirements and provides all necessary communication with the IRB/EC including, but not 
limited to, annual trial reports and required adverse event notifications. 
20.2. Investigator Records 
Case REPORT FORMS 
The standardized electronic Case Report Forms (eCRFs) will be used to collect complete and 
accurate records of the clinical data from the trial according to the Good Clinical Practice (GCP) 
requirements.  The Investigator is responsible for collecting and accurately recording the data 
generated for this trial. 
SCREENING LOG 
Investigators will maintain a screening log that will record the date of informed consent, the 
date of screening, the enrollment status (enrolled/excluded) and the reason for exclusion for all 
screen failures. 
20.3. Investigator Reports 
FINAL TRIAL REPORT 
A summary of the final report will be prepared and provided to each Principal Investigator for 
submission to their respective IRB after completion of the trial. 
SERIOUS ADVERSE EVENTS (SAES) 
The Investigators will report by eCRF any SAEs including serious, and/or potentially device- or 
procedure-related adverse events as soon as possible, within 24 hours of the Investigator 
becoming aware of the event, to the Sponsor and the Sponsor’s CRO and to the IRB as per the 
committee’s reporting requirements.  The Serious Adverse Event eCRF is to be completed and 
submitted to the Sponsor as initial notification.  
 
 
 

 
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DEVICE MALFUNCTIONS 
The Investigators will report by telephone, email or fax any Device Malfunctions as soon as 
possible, within 24 hours of the Investigator becoming aware of the event, to the Sponsor and 
the Sponsor’s CRO. 
WITHDRAWAL OF APPROVAL 
If an IRB withdraws the approval to conduct this trial for any reason, the Investigator will notify 
the Sponsor and the Sponsor’s CRO as soon as possible, but in no event later than five working 
days after the withdrawal of the approval. 

 
CARDIVA Medical, Inc. 
 
 
 
The AMBULATE Trial           CONFIDENTIAL                          PTL 0543-02   
 
 
21. Attachment 2: Sample Informed Consent Form  
 
 
 
 
 

 
CARDIVA Medical, Inc. 
 
 
 
The AMBULATE Trial           CONFIDENTIAL                          PTL 0543-02   
 
 
22. Attachment 3: Instructions For Use (IFU) 
  
 
 
 

Informed Consent_PTL 0543-01                                Page 1 of 8 
Participant Sample Consent Form 
 
Title of Study: “THE AMBULATE CAP STUDY” 
 
MULTI-CENTER, SINGLE ARM CONTINUING ACCESS PROTOCOL TO EVALUATE THE CARDIVA MID-BORE 
VENOUS VASCULAR CLOSURE SYSTEM (VVCS) FOR THE MANAGEMENT OF THE FEMORAL VENOTOMY 
AFTER CATHETER-BASED INTERVENTIONS PERFORMED VIA 6- 12 FR PROCEDURAL SHEATHS WITH 
SINGLE OR MULTIPLE ACCESS SITES PER LIMB  
 
 
Sponsor:  Cardiva Medical, Inc., Santa Clara, CA 
Principal Investigator:  
Institution:   
Your Consent 
You are invited to take part in this research project at (insert hospital / facility name). The purpose of this 
clinical study is to evaluate a new device designed to close the veins in your legs that will be punctured as 
part of your heart procedure. The devices are used at the end of the procedure.   This consent form will 
provide you with information about the study, the procedures that will be performed, and your rights.  
 
This consent form may contain words that you do not understand. Please ask the study doctor or the 
study staff to explain any words or information that you do not clearly understand.  You may take home 
a copy of this form so that you can think and discuss with your family, friends, or local health care provider 
before making a decision to take part in this study. 
Purpose & Background of the Study 
Your doctor has explained to you that you need a procedure to treat your irregular heart beat.  As part of 
this procedure, the doctor will put several holes in your leg veins in to order insert the medical equipment 
that is needed to perform the procedure. Once the doctor is finished with your procedure, these holes 
will need to be sealed (closed up) to prevent bleeding. You are being asked to participate in a research 
study to help evaluate the safety and effectiveness of a new vascular closure device developed by Cardiva 
Medical, called the Venous Vascular Closure System (VVCS). The device is used to close the leg vein holes 
that were punctured during your procedure. A small collagen (cotton-like) patch is placed just outside of 
the vein to plug the hole and stop the bleeding.  
Cardiva Medical developed a similar version of this device that is used to close holes in leg arteries called 
the VASCADE Vascular Closure System. The VASCADE device was tested in a large clinical study and 
approved by the U.S. Food and Drug Administration (FDA) in 2012, and has been used and sold in the 
United States since that time. 
The safety of the VASCADE device has been tested and proven in several previous research studies of over 
350 human patients without serious problems or deaths. The collagen patch is similar to other collagen-
based closure devices used in surgery to close small holes.  In a large FDA approval study called RESPECT, 
a total of 417 subjects were enrolled. Two-thirds (275 patients) received the VASCADE device, and one-

Informed Consent_PTL 0543-01                                Page 2 of 8 
third (142) received manual compression to close a single artery hole (femoral artery). Safety results were 
similar in both groups. 
 
The new device for this study (“study device”) has some minor changes to it that make it more suitable 
for use in closing holes in veins, and has recently been tested in a new clinical study to show that it has 
similar results to the VASCADE device. The AMBULATE Study included 204 patients who were 
“randomized” (50:50 chance) to receive either the study device or manual pressure to stop the bleeding 
in the veins after procedures, when 3 or 4 punctures were needed. An additional 42 “Roll-in” patients 
were treated with the study device as part of the physicians’ initial training. A total of 141 patients 
received the study devices, in 486 venous puncture sites. The results of this study have been submitted 
to the U.S. Food and Drug Administration (FDA) for review and potential marketing approval. While this 
review is underway, the FDA allows enrollment of additional patients in order to collect specific 
information about how physicians utilize the device in their practices, for their patients. 
If you choose to take part in the study, you will receive the study device to close off each of the leg vein 
holes. The collagen patch is still considered investigational for use in veins (not approved for sale). 
 
The doctors will follow similar patient selection guidelines as they did in the AMBULATE Study, but will be 
looking at three specific groups of patients in this CAP Study: 
 
• 
No urinary catheter: this means that when the study device is used to close the holes in the veins, 
a patient may not need a urinary catheter placed for the procedure or before hospital discharge 
because they may be able to get up and walk to the bathroom sooner.  
 
• 
No Protamine: this means that when the study device is used to close the holes in the veins, a 
patient may not have to receive a medication that reverses the effect of the IV blood thinners 
used during your procedure. You should still be able to walk sooner when this medication is not 
used. 
 
• 
Same Calendar Day Discharge: this means that when the study device is used, patients usually 
walk sooner and may be able to go home the same day as the procedure because of this. This will 
apply to specific types of procedures for safety reasons. The procedures included in this group are 
for treatment of atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, atrial 
flutter or a combination of these procedures. You will not be able to enroll in the No Protamine 
and Same Calendar Day Discharge groups at the same time, to reduce the chance of bleeding 
complications. 
 
This study will enroll about 300 patients at up to 5 hospitals in the United States. Your participation in this 
study will last 30 days (± 10 days). The expected total time for all patients to complete the study is about 
6 months.   
 
What happens if I say yes, I want to be in this research? 
If you agree to be in this study, the first step is signing of this consent form.  The following will then happen 
to you: 

Informed Consent_PTL 0543-01                                Page 3 of 8 
Pre-Procedure 
Before the procedure you will have a medical interview to make sure you qualify 
for the study (are eligible to take part in the study) and you will have your blood 
drawn (approximately 1-2 teaspoons) for laboratory testing (creatinine, platelet 
count, hemoglobin, hematocrit, INR if on warfarin). These are normal blood tests 
that are drawn before a procedure like yours. Your doctor will review your chart 
to see if you will qualify for at least one of the 3 groups. 
Procedure 
During the procedure your doctor will insert between 2 and 5 small plastic tubes 
to gain access to the large veins in both of your legs (femoral veins).  He/she will 
then insert small tubes of various sizes into each of these access sites so that the 
medical equipment needed to perform your heart procedure can be inserted into 
your body for use. Since you will receive blood thinning medications as part of 
your regular procedure, your doctor will monitor your blood to determine how 
long it takes you to stop bleeding. 
 
When your doctor is finished with the procedure and your doctor feels it is okay 
for you to take part in the study, he/she will decide if you qualify for enrollment. 
If yes, then he/she will proceed to close all of the holes in the veins with the 
Cardiva device. You may qualify to be in more than one of the “groups” at a time, 
which means that data specific to that “group” will be collected but does not 
require any additional effort from you. If your doctor decides that you do not 
qualify for the study, you will not be enrolled and will be treated according to 
your doctor’s normal practice. 
Post-Procedure 
After the procedure, the puncture site (place where the hole was made for the 
heart catheters) will be checked often to make sure it is not bleeding.    
 
After you get up to walk, but before you are discharged from the hospital the 
Research Coordinator will give you a short “Patient Experience Survey” to 
complete. The survey will ask you how you feel about the time you were on 
bedrest after your procedure. This is for the study only and will not be part of 
your medical records. 
30 days  
You will need to come in or have a telephone follow-up contact 30 (± 10) days 
after the procedure. You will be asked about the place where the holes were in 
your legs to make sure they have healed properly.   
These are normal steps used in this type of heart procedure.  The only difference is that your doctor will 
be using a device to close the venous holes to stop the bleeding instead of holding longer pressure on the 
holes to stop the bleeding. 
 
Possible Risks  
 
Possible side effects (problems) are similar to other closure devices and “manual compression”. Of the 
possible side effects listed below, there were no reports of these events occurring in the 275 VASCADE 
patients, except as noted for each event listed (i.e., % of patients experiencing an event): 
• 
allergic response (to the material in the device or collagen) 

Informed Consent_PTL 0543-01                                Page 4 of 8 
• 
arterio-venous fistula (abnormal connection between artery and vein) (0.4%) 
• 
bleeding/oozing from the puncture site (2.9%); bleeding requiring transfusion (0%) 
• 
bruising at the puncture site (<0.05%) 
• 
death 
• 
deep vein thrombosis (thrombus formation in a vein in the leg) (1%) 
• 
device failure / malfunction (4%) 
• 
edema (swelling in the tissues) 
• 
embolization (thrombus, air, calcific debris, device floating downstream) 
• 
hematoma (bleeding under the skin) (2%) 
• 
infection at the access site 
• 
inflammatory response (inflammation) 
• 
intimal tear / dissection (tear of the leg vein or artery wall) 
• 
laceration of the vessel wall 
• 
lower extremity ischemia (lack of oxygen to the leg) 
• 
peripheral nerve injury (nerve damage to the leg) (<0.05%) 
• 
perforation of the vessel wall (puncture of the vessel wall) 
• 
pseudoaneurysm (abnormal collection of blood with persistent flow outside an artery due to 
a leaking hole in the artery due to injury) (1.8%) 
• 
pulmonary embolism (blockage of an artery in the lungs) 
• 
puncture site pain (1%) 
• 
retroperitoneal bleeding (bleeding in the area behind the abdomen) (<0.05%) 
• 
vasospasm (spasm of the artery) 
• 
vasovagal response (slowed heart rate with possible fainting) 
• 
vascular injury requiring repair (vessel damage requiring repair)  
• 
vessel occlusion (blockage of the artery or vein) 
• 
vessel thrombus (blood clot in the artery or vein) 
• 
wound dehiscence (separation of wound edges) 
 
There are other general risks that are associated with your entire procedure, and your doctor will tell you 
about those separately. 
 
The risks to an unborn baby conceived during the study are unknown. Therefore, women in the study 
should practice acceptable pregnancy prevention methods during the study. Pregnant or lactating women 
cannot take part in the study. However, breastfeeding women may decide to stop nursing, after discussing 
it with their physician, in order to take part in the study. 

Informed Consent_PTL 0543-01                                Page 5 of 8 
 
Unknown risks: The risks of placing a vascular closure device are understood. However, there may be 
additional risks, which are unknown at this time. 
 
Possible Benefits 
 
There is no guarantee or promise that you will receive any benefits from the Cardiva VVCS. Potential 
benefits include rapid closure of the vein holes, which may increase your comfort after the procedure and 
may allow you to start walking sooner.  The doctors may learn more about how this device performs in 
veins.  There may also be other unexpected benefits that will be discovered as a result of this study, and 
any new significant information will be provided to you by your doctor. 
 
Financial Responsibility  
 
The study sponsor will pay the costs of tests, exams, and procedures that are performed only because you 
are in this study (are not part of your regular treatment). The cost for study devices used in this study will 
be billed by your hospital. You or your insurance company will be responsible for all costs of your usual 
ongoing medical care. This includes the cost of your procedure (including the study devices), hospital care 
and services, and any follow-up that would be performed as part of your medical care outside of this 
study. If your insurance company requires any co-payment or deductible, you will be responsible for 
making that payment.  You will not be paid for your participation in this clinical trial, and there is no 
financial reward or compensation in any form.  
 
Compensation for Injury 
 
In the event that you become ill or injured as a result of your taking part in this research project, the 
Hospital will provide you with medical treatment. If you are in the “study” group, and it is determined that 
your illness or injury resulted from the collagen patch (VVCS) in your leg(s), this medical treatment, as well 
as other reasonable and customary medical expenses, will be paid for by the sponsor of the study (Cardiva 
Medical), but only to the extent that the costs and expenses are not covered by your health insurance or 
a government program. This agreement to provide free medical treatment does not include costs and 
expenses for an illness or injury that does not result from the collagen patch (VVCS). No funds have been 
set aside to compensate you for such injuries. In addition, the sponsor of the study has not set aside funds 
to compensate you for non-direct damages such as lost of wages, disability, or discomfort due to illness 
or injury. No compensation or reimbursement is available from (insert institution) or the Sponsor.  
 
If you have any questions concerning the availability of medical care or if you think you have experienced 
a research related illness or injury, you should contact the research study doctor or other research study 
staff. The study doctor and sponsor will determine if the illness or injury may have resulted from the 
collagen patch you may have received. 
 
You will not give up your legal rights by signing this document. For instance, your legal right to claim 
compensation for illness or injury where you can prove negligence or malpractice will not be affected 
when you sign this form. 
 
Privacy, Confidentiality & Disclosure of Information 
 

Informed Consent_PTL 0543-01                                Page 6 of 8 
Your confidentiality will be maintained in accordance with the privacy and relevant health records laws of 
(insert state/providence). You have a right of access to, and to request correction of, information held 
about you by (insert facility name) in accordance with the (insert regulation).  Any information obtained 
in connection with this research project that can identify you will remain confidential and will only be used 
for the purpose of this research project.  It will only be disclosed to parties listed below with your 
permission, except as required by law.  
 
During the study only your initials and a unique study number will be used to identify you. Your name, 
address and any other personal information will not appear on any documents that are collected in 
relation to this research. It will not be possible to identify you from information in any publication resulting 
from this study and every effort will be made to keep your own personal medical data confidential to the 
extent allowed by law. 
 
By signing this consent form you agree that under direction of the study doctor, authorized 
representatives of the sponsor, Cardiva Medical, Inc. (the manufacturer of the study device), the 
Institutional Review Board, and the United States Food and Drug Administration (FDA) can access your 
health information in order to verify the accuracy of the data and verify compliance with the study 
procedures. By signing this Consent Form, you authorize release of, or access to, this confidential 
information to the relevant study personnel and regulatory authorities as noted above.  
 
All records kept from the study may be destroyed after 15 years, unless Cardiva Medical requests 
otherwise.  
 
New Information Arising During the Project 
 
During the research study, new information about the risks and benefits of the project may become 
known to the researchers. If this occurs, you will be told about this new information.  
 
Termination of the Study 
 
This research study may be stopped for a variety of reasons. These may include reasons such as: discovery 
of an unexpected, significant, or unacceptable risk to patients or a decision on the part of Cardiva Medical 
to suspend or discontinue development of the device.  
 
Right of Refusal and Alternative Treatments 
 
Participation in this study is voluntary.  You may refuse to participate in this study or discontinue 
participation at any time.  If you refuse to participate in this study, it will not affect the care your doctor 
will provide to you or result in any penalty or loss of benefits to which you are otherwise entitled.   
 
The only alternative to the Cardiva Medical VVCS device for closure of the vein puncture sites is use of 
another FDA-approved device, or manual compression (firm pressure). 
 
Also, your Study doctor or the sponsor may terminate your participation in the Study at any time, for 
reason, including these:  
• 
It would be dangerous for you to stay in the study 
• 
You have not followed the instructions of your study doctor and/or study staff  
• 
You become pregnant 

Informed Consent_PTL 0543-01                                Page 7 of 8 
• 
You need treatment not allowed in the study 
• 
The Sponsor decides to end the study 
• 
 Other unexpected circumstances 
 
Inquiries 
 
There are some technical terms used in this consent form.  If there is anything you do not understand, 
please ask your doctor or study nurse to explain.   
 
In case of emergency, or if you have any questions during this study about your rights as a research 
participant or the procedure, please contact:  
 
(add investigator name)    
(insert contact info) 
(add sub-investigators) 
(insert contact info) 
 
 
(add coordinators) 
(insert contact info) 
 
 
 
 
 
A description of this clinical trail will be available on http://www.clinicaltrials.gov, as required by U.S. Law.  
This Web site will not include information that can identify you.  At most, the Web site will include a 
summary of the results.  You can search this Web site at any time.  
 
Study Participant’s Bill of Rights 
Persons who participate in a medical experiment are entitled to certain rights. These rights include but 
are not limited to the subject's right to: 
• 
Be informed of the nature and purpose of the experiment 
• 
Be given an explanation of the procedures to be followed in the medical experiment, and any drug 
or device to be utilized 
• 
Be given a description of any attendant discomforts and risks reasonably to be expected 
• 
Be given an explanation of any benefits to the subject reasonably to be expected, if applicable 
• 
Be given a disclosure of any appropriate alternatives, drugs, or devices that might be given 
advantageous to the subject, their relative risks, and benefits 
• 
Be informed of the avenues of medical treatment, if any, available to the subject after the 
investigational procedure if complications should arise; 
• 
Be given an opportunity to ask questions concerning the experiment or the procedures involved 
• 
Be instructed that consent to participate in the medical experiment may be withdrawn at any 
time and the subject may discontinue participation without prejudice 
• 
Be given a copy of the signed and dated consent form 
• 
Be given the opportunity to decide to consent or not to consent to a medical experiment without 
the intervention of any element of force, fraud, deceit, duress, coercion, or undue influence on 
the subject's decision. 
 
Consent 
 
 

Informed Consent_PTL 0543-01                                Page 8 of 8 
Your signature below indicates that: 
• 
You have read and understood the above information. 
• 
You have discussed the study with your study doctor. 
• 
You have had a chance to ask all of your questions and have had them answered. 
• 
You have decided to take part in the study based on the information aprovided. 
• 
A copy of this form has been given to you. 
 
 
 
 
 
 
_____/_____/_____ 
Signature of Participant  
 
Date  
 
 
 
 
Printed Name of Participant  
 
 
 
 
 
 
_____/_____/_____ 
Signature, Person Conducting Informed Consent Discussion 
 
Date  
 
 
 
 
Printed Name, Person Conducting Informed Consent Discussion 
 
 
 
 
 

Page 1 of 8 
 
  
VASCADE® MVP  
MID-BORE Venous Vascular Closure System (VVCS) Model 800-612C 
INSTRUCTIONS FOR USE 
IFU 3972 Rev - B 
For Investigational Use Only 
 
CAUTION – Federal (USA) law restricts this device to sale by or on the order of a physician 
DESCRIPTION 
The MID-BORE Venous Vascular Closure System (VVCS) Model 
800-612C is intended to seal the femoral vein access site(s) at 
the completion of the procedure.  The system is designed to 
deliver a resorbable Collagen Patch, extra-vascularly, at the 
venotomy site to aid in achieving hemostasis.  The device can 
be used in 6F to 12F, 12cm1 introducer sheaths. The system 
consists of a sterile disposable Vascular Closure Catheter which 
houses a resorbable Collagen Patch, and the MID-BORE VVCS 
Clip (refer to Figure 1). The collagen patch is composed of type 
I Bovine collagen and is delivered in a compressed form that is 
approximately 15mm in length.  The dry weight of the collagen is 
12mg ± 3mg.   The patch expands as a result of rehydration 
in the presence of blood in the tissue tract to provide an 
extravascular seal.  A radiopaque proximal marker band on the 
Catheter provides means to aid in verifying placement of the 
patch in the tissue tract adjacent to the femoral venotomy site 
prior to the release of the patch.  A second distal marker band 
locates the distal tip of the MID-BORE VVCS Disc. After 
completion of the procedure, the MID-BORE VVCS Catheter is 
inserted through the introducer sheath.  The MID-BORE VVCS 
Disc is then deployed within the vessel and the introducer sheath 
is removed over the MID-BORE VVCS Catheter.  After the 
introducer sheath is removed, the MID-BORE VVCS Disc is 
positioned against the intimal aspect of the venotomy, providing 
both temporary hemostasis and protection from intravascular 
placement of the Collagen Patch, and the MID-BORE VVCS Clip 
is applied at skin level to maintain the position of the Disc. After 
confirming the 
position of 
the 
Collagen 
Patch either 
fluoroscopically or by ultrasound, the Black Sleeve is unlocked 
and retracted to expose the Collagen Patch to the tissue tract. 
The system is left in place for a brief dwell period to allow the 
patch to swell, after which the  Disc is collapsed and the MID-
BORE  VVCS Catheter is removed from the vein leaving the 
resorbable, extra-vascular, hemostatic Collagen Patch at the 
venotomy site providing hemostasis. 
 
 
 
INDICATIONS FOR USE 
The MID-BORE Venous Vascular Closure System (VVCS) Model 800-612C is indicated for the percutaneous closure of 
femoral venous access sites while reducing times to ambulation and discharge eligibility in patients who have undergone 
interventional catheter-based procedures utilizing 6 – 12 F procedural sheaths with single or multiple access sites, ranging 
from a single access site in one limb to multiple access sites in both limbs. 
 
 
Fig. 1 – MID-BORE Venous Vascular Closure System (VVCS) 

Page 2 of 8 
 
CONTRAINDICATIONS 
The MID-BORE VVCS should not be used in patients with a known allergy to bovine derivatives. 
 
WARNINGS 
• 
Do not reuse or re-sterilize. The MID-BORE VVCS is intended to be used once only for a single patient. Product 
reuse or re-sterilization, may result in transmission of infectious or blood borne diseases and/or death. 
• 
Do not use if components or packaging appear to be damaged or defective or if any portion of the packaging has 
been previously opened.  Damaged or opened packages may compromise product functionality. 
• 
Do not use if product is beyond the expiration date.  Product performance has not been established beyond the 
labeled shelf life. 
• 
Do not deploy the MID-BORE VVCS Disc in a stent. Do not pull the deployed MID-BORE VVCS disc through a stent.  
Damage to the product may occur. 
• 
Do not use MID-BORE VVCS if access is through a previously placed permanent closure device such as a metal 
clip.  Interference between the two closure devices may result. 
• 
Do not deploy the Collagen Patch if there is a suspicion that the MID-BORE VVCS Disc is not seated against the 
intimal aspect of the venotomy site.  Partial or complete obstruction of blood flow may result. 
• 
Do not deploy a second collagen patch at the same access site within 30 days.  Safety has not been established. 
 
PRECAUTIONS 
• 
The MID-BORE VVCS should only be used by a trained licensed physician or healthcare professional. 
• 
Do not use in access sites where there is suspicion of a “backwall” stick.  Increased bleeding risk may occur. 
• 
Do not use if venotomy is noted to be a “side stick.”  Bleeding risk may increase. 
• 
Do not use if venotomy site is noted to be “high,” above the Inguinal Ligament (cephalad to lower half of the 
femoral head or the inferior epigastric artery origin from the external iliac artery).  This may increase the risk of 
bleeding. 
• 
Do not use in a vein with suspected intraluminal thrombus, hematoma, pseudoaneurysm, or arteriovenous fistula.  
These conditions may complicate proper device use and performance. 
• 
Do not use if intra-procedural bleeding around the introducer sheath is noted including hematoma formation (sign 
of possible multiple wall stick).  This may suggest problems with the access site. 
• 
Do not use in a procedural sheath > 12cm in length (or >15cm in overall length) or with a diameter other than 6-
12F. This may complicate disk deployment. 
 
SPECIAL PATIENT POPULATIONS 
NOTE: The safety and effectiveness of MID-BORE VVCS have not been evaluated in the 
following patients who are/have: 
• 
Less than 18 years of age; 
• 
Pregnant and/or lactating women; 
• 
Pre-existing immunodeficiency disorder and/or chronic use of systemic steroids; 
• 
Known significant coagulopathy/bleeding disorder such as thrombocytopenia (platelet count <100,000/mm³), 
thrombasthenia, hemophilia, von Willebrand’s disease or anemia (Hemoglobin <10g/dL, Hematocrit <30%); 
• 
Previous vascular grafts or surgery at the target vessel access site; 
• 
Symptomatic ipsilateral lower extremity ischemia; 
• 
Femoral venous lumen less than 6 mm; 
• 
Length of the tissue tract, the distance between the anterior venous wall and skin, is estimated to be less than 
2.5cm; 
• 
INR ≥1.8 if patient received warfarin; 
• 
Fibrinogen level < 150 mg/dl if patient received fibrinolytic agent; 
• 
Extreme morbid obesity (BMI > 45 kg/m2) or underweight (BMI < 20 kg/m²); 
 
 
 
 

Page 3 of 8 
 
 
Adverse Events 
Complications may occur and may be related to the procedure or the vascular closure. They include, but are not 
limited to: 
• Allergic response 
• Embolization tissue,  
• Laceration of the vessel wall 
• Vascular occlusion 
(thrombus, air, calcific debris 
• Peripheral nerve injury 
• Venous thrombus 
    device) 
• Pseudoaneurysm 
• Arterio-venous fistula 
• Pulmonary Embolism  
• Retroperitoneal bleeding 
• Bleeding from the puncture site 
• Hematoma 
• Deep vein thrombosis 
• Oozing from the puncture site 
• Infection 
• Vascular injury 
• Bruising at the puncture site 
• Inflammatory response 
• Vasovagal response 
• Death 
• Intimal tear / dissection 
• Wound dehiscence 
• Device failure/malfunction 
• Lower extremity ischemia 
• Puncture site pain 
• Superficial vein thrombosis  
• Edema 
• Perforation of the vessel wall 
 
 
 
 
DEVICE PREPARATION AND PROCEDURE 
 
At the time of initial access, if more than one sheath is planned to be placed in the same vein, the distance between the 
access sites should be kept at a minimum of 6 mm.  Keep the stick separation at the skin level at a minimum of 6 mm and 
drive the needles to the vein at the same angle to keep the separation between the adjacent venotomies at a minimum of 6 
mm.  Imaging techniques such as ultrasound to confirm the separation is recommended. 
 
At the time of initial introducer sheath placement, patient body habitus should be evaluated to provide reasonable 
assurance that the distance between the femoral venotomy and the skin surface is greater than 2.5cm.  After introducer 
sheath placement, an anterior oblique fluoroscopic image with contrast or an ultrasound image may be digitally recorded 
and stored, so that the venotomy site location can be estimated and compared to the position of the proximal radiopaque 
marker just prior to Collagen Patch release. The proximal radiopaque marker is located immediately distal to the Collagen 
Patch. If more than one sheath is used in the same vein, it is recommended to close the proximal venotomy first to facilitate 
device placement and imaging prior to Collagen Patch release.  
 
CAUTION: During access care should be taken so that the tissue tract is not pushed laterally or medially prior to accessing 
the vessel. This is to avoid misalignment of the tissue tract and the Collagen Patch relative to the venotomy site once the device 
is removed from the vessel which may result in prolonged time to hemostasis.   
If more than one access is made in the vein, keep a minimum of 6 mm separation between the access sites.  This is to allow 
the disc to track back to the vessel wall.  Temporary hemostasis may not be achieved if the venotomies are too close to each 
other. 
Not achieving temporary hemostasis may be an indication that the disc is not against the vessel wall.  Releasing the collagen 
patch may result in all or a portion of the patch to be deployed in the vessel. 
 
1. Use the Cardiva MID-BORE VVCS only as described below: 
Device 
Model 
Sheath Size 
(French) 
Sheath 
Length 
Disc Size 
Collagen 
Patch 
Length 
Device Working 
Length 
Maximum OD 
(with 
collapsed 
Disc)  
Cardiva MID-BORE VVCS 
800-612C 
6F – 12F 
up to 12 cm 
7.7 mm 
15 mm 
15 cm 
2.1 mm 
 
2. Inspect the package for damage (breaks, tears, open seals, water damage, etc.) and verify that expiration date 
has not passed. 
 
3. Using standard sterile technique, remove the tray containing the MID-BORE VVCS Catheter and Clip from the 
foil pouch.  Carefully remove MID-BORE VVCS Catheter and Clip from the tray.  Examine the device by first 
verifying that the Black Sleeve is locked in position and the Collagen Patch is not exposed.  Also verify that the 
Yellow-Blue Key (Figure 2) is not engaged in the Lock (the Lock is located at the proximal aspect of the Black 
Sleeve), and the Yellow-Blue Key is located at the proximal end of the Catheter Shaft.  Inspect the Catheter further 
by examining the deployed MID-BORE VVCS Disc.  To deploy the Disc, hold the Silver Handle firmly and pull back 

Page 4 of 8 
on the Black Actuator until it locks in place.  When the Disc is locked in the deployed position, the Green Segment 
will become visible as shown in Figure 3.  Examine the Disc, which should appear circular and symmetrical 
with an intact membrane.  Figure 4 shows the deployed and collapsed Disc.  After examination, collapse the Disc 
by pressing the Black Actuator tip down (Figure 5).  The tip of the MID-BORE VVCS Catheter should return to its 
original profile. 
 
 
 
 
 
 
Fig. 2 – Verify Yellow-Blue Key is not 
engaged in the Lock and Black Sleeve 
is locked in position 
Fig. 3 – Pull back on Black Actuator 
Tip to deploy the Disc 
Fig. 4 – Deployed & Collapsed Disc 
Fig. 5 – Collapse Disc by pressing 
Black Actuator Tip like a ballpoint pen 
 
4. Verify that the sheath is not positioned in a tortuous vessel, by examining the sheath placement images obtained 
earlier.  If required, retract the sheath slightly to a non-tortuous location.  Verify that the sheath is still positioned 
within the vein.  If more than one sheath is in the vein, retract the most proximal sheath (top sheath) so that the 
distal opening of that sheath is proximal to the distal opening of other sheaths by 3-4 cm.  This is to eliminate 
interference of a deployed disc with other indwelling sheaths during device deployment.  Care must be taken not 
to lose vessel access. Deploy MID-BORE VVCS and obtain hemostasis in the most proximal sheath first (as per 
steps outlined below).  Then move distally to repeat the steps to obtain closure for the other sheaths.   
WARNING:  Verify there is no vessel tortuosity or side branches within 3-4 cm from the distal opening of the sheath and the 
end of the sheath is not resting against the vessel wall.  This is to prevent any vascular injury as a result of advancing the 
catheter.  If required, retract the sheath slightly to a non-tortuous location, being careful not to lose vessel access. 
 
5. Flush the sheath with sterile saline solution prior to insertion of the device. 
6. Prior to insertion of device in the introducer sheath, momentarily insert the tip of the VVCS Catheter in saline 
solution up to the White Marker Stripe and quickly remove. 
 
CAUTION: Do not soak the MID-BORE VVCS Catheter in saline. Momentarily insert only the Catheter tip in saline 
solution immediately before use to avoid over-hydration of the patch, which may result in difficulty of retracting the sleeve 
and causing Catheter pull through during the sleeve retraction step. 
 
7. Gently insert the MID-BORE VVCS Catheter (with disc collapsed) into the introducer sheath hub as shown in 
Figure 6. Use short strokes to insert the device.   
8. Insert the MID-BORE VVCS Catheter such that approximately half of the Lock is visible.  Make certain that the 
Lock is NOT fully inserted into the sheath.  See Figure 7 for correct placement. 
 
CAUTION: Do not advance MID-BORE VVCS Catheter into the patient if resistance is felt due to risk of vascular 
damage. 
 
 
 
Fig. 6 – Insert device into hub of 
introducer sheath 
 
Fig. 7 – Insert device half way of the 
Lock 
 
Fig. 8 – Pull back on Black Actuator 
Tip to deploy the MID-BORE VVCS 
Disc 
 
Fig. 9 – Grasp hub of sheath and 
remove over catheter 
 
 

Page 5 of 8 
9. Deploy the Disc by holding the Silver Handle and pulling back the Black Actuator until it locks in place as shown 
in Figure 8. 
 
CAUTION: Do not continue to pull on the Black Actuator once it is locked in place as this may damage the device. 
 
NOTE: When the Disc is properly deployed, the Green Segment will become visible distal to the Black Actuator.  If 
the catheter is not properly locked in place, the Black Actuator will slide back to its original position and the Green 
Segment will disappear indicating that the Disc is not properly deployed.  In this case repeat the step for deploying the 
Disc by pulling the Black Actuator more firmly until it locks in place. 
 
10. Gently remove sheath, without applying any compression at the access site or holding the MID-BORE VVCS 
Catheter, as shown in Figure 9.  As the sheath slides over the MID-BORE VVCS Catheter, grasp the Catheter as 
the sheath exits the body.  Continue sliding the sheath over the MID-BORE VVCS Catheter and discard sheath. 
 
CAUTION: Compressing the access site during sheath removal may not allow the Disc to track back to the venotomy and may cause 
Disc deformation. This may lead to inability to achieve temporary hemostasis. 
 
11. Apply gentle tension on the Black Actuator until temporary hemostasis is achieved.  Note whether any portion of 
the White Marker Stripe, which is located near the distal aspect of the Black Sleeve, is visible above the skin.  If it 
is, then the length of the tissue tract is less than 2.5 cm, indicating the tissue tract may not be long enough for the 
Collagen Patch. 
 
WARNING:  If any portion of the White Marker Stripe is showing DO NOT RELEASE the Collagen Patch as this may increase 
the risk of infection. 
 
NOTE:  If any portion of the White Marker Stripe is showing and the collagen patch is not to be deployed, the MID-
BORE VVCS Catheter should be removed by collapsing the Disc and manual compression should be applied per 
institutional protocol. 
 
12. Once temporary hemostasis is achieved, apply the Clip to the Black Sleeve at skin level as shown in Figure 10.  
Verify that deployed Disc is positioned against the intimal surface of the vessel at the venotomy site, 
either by fluoroscopy (to verify that the more proximal radiopaque marker is positioned at the venotomy), 
or by ultrasound. The Collagen Patch is located immediately proximal to the Proximal Marker Band.  The Distal 
Marker Band locates the distal end of the Disc. 
 
CAUTION: Applying too much upward tension on the Silver Handle may cause disc to pull out of vessel.  Should this occur, 
convert to your institution’s manual compression protocol. 
WARNING: It is important to ensure that the Disc is in contact with the intimal aspect of the venotomy before deploying the 
extra- vascular Collagen Patch to avoid releasing the Collagen Patch in the vessel.  This is indicated by having temporary 
hemostasis and further verified by either fluoroscopy (Figure 11a) or ultrasound imaging (Figure 11b).  
 
 
 
 
 
Fig. 10 – Apply Clip to Black Sleeve at 
skin level 
Fig. 11a – Fluoroscopic image demonstrating proper position of Disc  
Figure 11b Ultrasound image demonstrating proper 
position of Disc 
 

Page 6 of 8 
 
EXTRA-VASCULAR COLLAGEN PATCH DEPLOYMENT AND DEVICE REMOVAL 
13. Once the Disc location is verified, expose the extra-vascular resorbable Collagen Patch by unlocking the Black 
Sleeve.  This is done by grasping the Lock with the left hand, between the thumb and the index finger, and 
grasping the Yellow-Blue Key with the right hand and then sliding the Yellow-Blue Key into the Lock until no 
blue color is visible, as shown in Figure 12.  Once the Sleeve is unlocked and while still holding on to the Lock, 
remove the Clip with the right hand, and gently slide the Lock back along the angle of entry to retract the Black 
Sleeve as shown in Figure 13.  The Black Sleeve will move freely after some initial resistance.  A second 
resistance point may be felt after the sleeve is moved approximately 1.6 cm (0.6 inch). 
Proceed to fully retract the Black Sleeve proximally to the Silver Handle.  This action exposes the Collagen 
Patch extra-vascularly, which will swell at the venotomy site.  The Collagen Patch may be allowed to swell for 
up to 30 seconds prior to removal of the MID-BORE VVCS Catheter.  The Clip may be reapplied during the 
Collagen Patch swell period with minimal tension on the Catheter (Figure 14). 
 
NOTE: If the Black Sleeve does not retract easily, recheck that the blue end of the Yellow-Blue Key is fully engaged 
in the Lock. 
 
NOTE: If the Collagen Patch is removed during sleeve retraction, collapse the Disc, remove the Catheter and apply 
manual compression, per institutional protocol.   
 
 
 
 
 
 
 
Fig. 12 – Unlock the Black Sleeve 
by sliding Yellow-Blue Key into the 
Lock 
Fig. 13 – Retract the Black Sleeve 
by grasping the Lock and applying 
gentle upward tension toward the 
Silver Handle 
Fig. 14 – Reapply Clip during the 
Collagen Patch swell period 
Fig. 15 – Grasp Green Tube 
prior to collapsing the Disc 
Fig. 16 – Collapse the Disc by 
pressing on the Black 
Actuator Tip 
 
14. AFTER 15-30 seconds of patch swell time and PRIOR TO collapsing the Disk, remove the Clip. Rest the palm of 
the hand on the patient and grasp the green tube between the thumb and the index finger as shown in Figure 15. 
Push the green tube in the proximal direction approximately 1.5 cm while gently pulling back on the MID-BORE 
VVCS Catheter to maintain Disk position against vessel wall.  The green tube may be slid back and forth 2-3 times 
in order to assure release of the Collagen patch from device.  Upon completion of this step, leave the green tube in 
the forward position.  Apply gentle compression at the site and collapse the Disc by pressing on the Black Actuator 
Tip as shown in Figure 16. Apply gentle manual compression at the site as the MID-BORE VVCS Catheter is 
removed.  Continue to apply manual compression. 
 
15. Observe for complete hemostasis.  Manual compression can be used to decrease or stop any tract ooze until full 
hemostasis is achieved. 
 
NOTE:  Prior to the MID-BORE VVCS Catheter removal confirm that the Disc is completely collapsed by verifying 
that the Green Segment on the handle is no longer visible.  Care should be taken not to compress too firmly 
over the VVCS catheter during the removal step of the device so that the catheter can be easily removed and 
without displacement of Collagen Patch.  Note: The implanted Collagen Patch should not be affected by Magnetic 
Resonance Imaging (MRI). 
 
16. Apply sterile dressing to site per institution protocol. Maintain bed rest and periodically check site until patient is 
ready to ambulate. 
17. Complete information on Patient Implant Card and provide to the patient. 
 

Page 7 of 8 
 
GRAPHICAL SYMBOLS ON THE MID-BORE VVCS PACKAGING 
 
Do not reuse 
 
Store at room 
temperature 
Manufacturer 
 
Sterilized using 
irradiation 
 
Latex Free 
 
Authorized 
representative 
in the European 
Community 
 
Use by 
 
Lot Number 
 
Keep Dry 
 
Caution, see 
Instructions for 
Use 
 
Model Number 
 
Do not use if 
the product 
sterilization 
barrier or its 
packaging is 
compromised 
Quantity of 
systems in 
package 
 
Federal (USA) 
law restricts this 
device to sale 
by or on order 
of a physician 
Rx Only 
 

Page 8 of 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Design for what’s humanly possible 
 
 
 
 
 
 
Cardiva Medical, Inc. 
2900 Lakeside Drive, Suite # 160 
 Santa Clara, CA 95054 
USA 
Tel:  +1 408-470-7170 
US Toll Free Tel: 1-866-602-6099 
US Toll Free Fax: 1-866-602-1795 
 
www.cardivamedical.com 
 
Authorized Representative: 
MedPass International Ltd. 
Bretforton, Evensham, Worcestershire., 
 WR11 7JJ,United Kingdom 
Tel/Fax: +44 (0) 14 52 619 222 
medpass.ar@medpass.org 
 
 
LIMITED WARRANTY 
Cardiva Medical, Inc. warrants that each Mid-Bore Venous Vascular Closure System (VVCS) is free from defects in workmanship and material under 
normal use and service, and provided it is used prior to the stated expiration date.  Cardiva Medical, Inc. will not be liable for any incidental, special or 
consequential loss, damage or expense direct or indirect from the use of its product.  Liability under this warranty is limited to refund or replacement of 
any device that has been found by Cardiva Medical, Inc. to be defective at the time of shipment.   Damage to the device through misuse, alteration, 
improper storage or improper handling shall void this limited warranty.  The remedies set forth in this warranty and limitation shall be the exclusive 
remedy available to any person.  No employee, agent or distributor of Cardiva Medical, Inc. has any authority to alter or amend this limited warranty, 
or assume or bind Cardiva Medical, Inc. to any additional liability or responsibility with respect to this device. There is no express or implied warranty, 
including any implied warranty of merchantability or fitness for a particular purpose, on the Cardiva Medical, Inc. product(s) described herein. 
 

 
CARDIVA Medical, Inc. 
 
 
 
The AMBULATE Trial           CONFIDENTIAL                          PTL 0543-02   
 
 
23. Attachment 4: Patient Experience Survey 
 
 

AMBULATE Study PTL 0543 
SUBJECT ID: 
- 
SUBJECT INITIALS: 
 
SITE # 
SUBJECT # 
F 
M 
L 
Rev A_AMBULATE_CAP STUDY - Patient Experience Survey 
Page  
1 
Patient Experience Survey 
Instructions to the Research Staff: 
•
For all subjects following successful ambulation, please provide the following survey pages
to the subject under evaluation.
•
The Survey should be read and answered in order.
•
On completion of the survey, review for completeness and clarity. Make sure answers are
logical and clearly answered.
•
On completion of all applicable survey questions, enter the data in the eCRF and file source
documents.
Instructions to the Patient:  
•
Enter the date and time that you completed the survey at the top of the form.
•
INITIAL the bottom of each form when you complete it.
•
Please read the questions and respond by circling only one number from 0-10 on the scale
below each question, or by answering the specific question.
Examples: 
Correct 
Incorrect 
Printed name of person providing survey to the subject 
/ 
Signature 
Date 

         AMBULATE CAP Study PTL 0543 
SUBJECT ID:
- 
SUBJECT INITIALS:
SITE # 
SUBJECT # 
F 
M 
L 
Patient Experience Survey
Patient Experience Survey – draft 
 SUBJECT INITIALS:_________
Page 1 
Time & Date Form Completed: 
______/______/______  (dd-Mmm-yyyy) 
Enter Time: ______:______ 
1. Rate level discomfort in your groin at the catheter access site(s):
1 
 2 
 3 
 4 
 5 
 6 
 7 
  8 
 9 
 10 
1- (No Discomfort) 
5 - (Moderate Discomfort) 
10 - (Very Painful) 
2.
Which of the following best describes your bedrest
experience?
 Bedrest was too short. I wasn’t ready to walk yet. 
 Bedrest was just right 
 Bedrest was too long. I wanted to walk sooner. 
3.
Have you ever had an ablation procedure prior to this?
 Yes, complete a. – d. 
 No 
a.
How many ablation procedures have you had within:
(Please answer all questions. Enter 0 if none.)
The last year: _______ 
1-3 years ago: _______
4-5 years ago: _______
b.
The length of my current procedure’s bedrest was:
(select one)
 Longer 
 Shorter 
 Same 
 I don’t recall 
c.
Which most closely describes my experience for my
current procedure’s bedrest? (select one)
 I prefer my current procedure’s bedrest   
 I prefer my previous procedure’s bedrest 
 No preference 
 I don’t recall 
d.
My current procedure groin access site pain/discomfort
is: (select one)
 Better 
 Worse 
 Same 
 I don’t recall 

         AMBULATE CAP Study PTL 0543 
SUBJECT ID:
- 
SUBJECT INITIALS:
SITE # 
SUBJECT # 
F 
M 
L 
Patient Experience Survey
Patient Experience Survey-draft 
 SUBJECT INITIALS:_________
Page 2 
4.
Provided your physician felt it was medically safe, which
of the following do you prefer? (select one)
 Go home the same day   
 Spend an additional night in the hospital 
 No preference 
a.
If additional night, why? (select all that apply)
 No transportation 
 Too late 
 Still concerned about safety, despite physician’s assurance 
 Need additional support, 
specify:__________________________ 
5.
For post-procedure care, rate how important the following are to you:
a.
Ability to walk within 2-3 hours post procedure and not be confined to bedrest
1 
 2 
 3 
 4 
 5 
 6 
 7 
  8 
 9 
 10 
1- (Not Important) 
5 - (Important) 
10 - (Very Important) 
b.
Ability to urinate post procedure unassisted (for example: no urinary catheter, bedpans, etc.):
1 
 2 
 3 
 4 
 5 
 6 
 7 
  8 
 9 
 10 
1- (Not Important) 
5 - (Important) 
10 - (Very Important) 
c.
Ability to go home within the same calendar day and not spend the night in the hospital:
1 
 2 
 3 
 4 
 5 
 6 
 7 
  8 
 9 
 10 
1- (Not Important) 
5 - (Important) 
10 - (Very Important) 
6.
If you require a future procedure, would you actively seek a facility:
a.
That would allow you to walk within 2-3 hours post procedure and not be
confined to bedrest?
 Yes 
 No 
b.
That would not utilize a urinary catheter for urinary management?
 Yes 
 No 
c.
That would allow you to be discharged within the same calendar day if medically
appropriate?
 Yes 
 No 
Name: 
Signature: 
Date: 

CARDIVA Medical, Inc. 
CAROIVA MEDICAL, INC. 
Protocol Approval Page 
STUDY mLE:
"AMBULATE CAP STUDY" CoNTINUED ACCESS PROTOCOL (CAP) 
Mum-CENTER, SINGLE ARM CoNTINUING ACCESS PROTOCOL TO EVAWATE THE 
CARDIVA MID-BORE VENOUS VASCULAR CLOSURE SvmM (WCS) FOR THE 
MANAGEMENT OF THE FEMORAL VENOTOMY AmR CATHmR-BASED 
INTERVENTtONS PERFORMED VIA 6- 12 FR PROCEDURAL SHEATHS WITH SINGLE 
OR MULTIPLE ACCESS SITES PER LIMB 
PROTOCOL 
PTL 0543 
NUMBER: 
VERSION NUMBER: 
02 
We, the undersigned, have read and approve the protocol specified above and agree on Its content. 
Name/Title 
Justin Ballotta 
Chief Operating Officer 
Zia Vasslnzadeh 
Chief Technology Officer 
Jennifer Lee 
Signature 
Date 
Director, Quality & Engineering 
Č 
_ 
Terry Passaretti 
""\\_ č 
1 /t 3/ 18
Director, Regulatory & Clinical Affairs 
-➔,-------------------
Marlys Chellew, BSN 
Independent Cllnlcal Consultant 
f11M/4tJ {fvJhw 
rja9/(ct 
The AMBULATE CAP Study 
CONFIDENTIAL 
PTL0S43-02 
CIP Page Z of 67