Who is the manufacturer of CORDIS EXOSEAL VASCULAR CLOSURE DEVICE?

Cordis US Corporation filed the PMA application for CORDIS EXOSEAL VASCULAR CLOSURE DEVICE (P100013).

What is the FDA product code for CORDIS EXOSEAL VASCULAR CLOSURE DEVICE?

MGB. as a Class 3 device in the Cardiovascular panel.

Who can help prepare an FDA PMA submission like CORDIS EXOSEAL VASCULAR CLOSURE DEVICE?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA PMA submissions. See https://innolitics.com/services/regulatory/ or contact https://innolitics.com/contact.

CORDIS EXOSEAL VASCULAR CLOSURE DEVICE

P100013 · Cordis US Corporation · MGB · May 19, 2011 · Cardiovascular

Device Facts

Record ID	P100013
Device Name	CORDIS EXOSEAL VASCULAR CLOSURE DEVICE
Applicant	Cordis US Corporation
Product Code	MGB · Cardiovascular
Decision Date	May 19, 2011
Decision	APPR
Device Class	Class 3
Attributes	Therapeutic

Intended Use

The EXOSEAL Vascular Closure Device (VCD) is indicated for femoral artery puncture site closure, reducing times to hemostasis and ambulation in patients who have undergone diagnostic or interventional catheterization procedures using a standard 5F, 6F, or 7F vascular sheath introducer with up to 12 cm working length. Additionally, the EXOSEAL VCD is indicated to reduce times to hemostasis and ambulation in patients who have undergone interventional catheterization procedures, using a standard 6F vascular sheath introducer up to a 12 cm working length, who have received preprocedural and/or intraprocedural glycoprotein (GP) IIb/IIIa inhibitor therapy.

Device Story

EXOSEAL VCD consists of a Plug Applier and an absorbable Polyglycolic Acid (PGA) Plug. Used in cath labs by physicians to close femoral artery access sites post-catheterization. The device is inserted into the existing sheath introducer; a bleed-back indicator confirms vessel position. A nitinol wire provides feedback on plug placement relative to the vessel wall. Upon button depression, the device deploys the PGA plug extravascularly to the arteriotomy site. The plug is fully resorbed within 60-90 days. The device reduces time to hemostasis and ambulation compared to manual compression, potentially facilitating earlier hospital discharge.

Clinical Evidence

Pivotal data from the 6F ECLIPSE Trial (n=401 randomized) and pooled German/Mexican 7F studies (n=88). Primary endpoints: major complications (30 days), time to hemostasis, and time to ambulation. Results: 0% major adverse events in all groups. Mean time to hemostasis significantly lower for EXOSEAL (4.38 min 6F; 3.25 min 7F) vs. manual compression (20.05 min). Mean time to ambulation significantly lower for EXOSEAL (2.54 hr 6F; 2.64 hr 7F) vs. manual compression (6.24 hr).

Technological Characteristics

System includes a Plug Applier (Handle Assembly, Delivery Shaft) and an absorbable Polyglycolic Acid (PGA) Plug. Compatible with 5F, 6F, 7F sheaths up to 12 cm. Features include a bleed-back indicator and nitinol indicator wire for positioning. Sterilized via Electron Beam (E-Beam) irradiation. Biocompatibility confirmed per ISO 10993.

Indications for Use

Indicated for femoral artery puncture site closure in patients (≥18 years) undergoing diagnostic or interventional catheterization procedures via 5F, 6F, or 7F sheaths (up to 12 cm length). Includes patients receiving GP IIb/IIIa inhibitor therapy (6F only). Contraindications include pregnancy, lactation, known material allergy, severe systemic disease, or specific vascular/bleeding disorders.

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P010049 — QUICKSEAL FEMORAL ARTERIAL CLOSURE SYSTEM · Sub-Q, Inc. · Mar 25, 2002
P040044 — MATRIX VASCULAR CLOSURE SYSTEM (VSG) · Cordis US Corporation · Aug 17, 2005
P050007 — STARCLOSE VASCULAR CLOSURE SYSTEM · Abbott Vascular Devices · Dec 21, 2005

Submission Summary (Full Text)

{0} SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) I. GENERAL INFORMATION Device Generic Name: Vascular Closure Device Device Trade Name: EXOSEAL™ Vascular Closure Device Applicant: Cordis Corporation 430 Route 22 East Bridgewater, NJ 08807-0908 Date of Panel Recommendation: None Premarket Approval Application (PMA) Number: P100013 Date of FDA Notice of Approval: May 19, 2011 Expedited: Not applicable II. INDICATIONS FOR USE The EXOSEAL Vascular Closure Device (VCD) is indicated for femoral artery puncture site closure, reducing times to hemostasis and ambulation in patients who have undergone diagnostic or interventional catheterization procedures using a standard 5F, 6F, or 7F vascular sheath introducer with up to 12 cm working length. Additionally, the EXOSEAL VCD is indicated to reduce times to hemostasis and ambulation in patients who have undergone interventional catheterization procedures, using a standard 6F vascular sheath introducer up to a 12 cm working length, who have received preprocedural and/or intraprocedural glycoprotein (GP) IIb/IIIa inhibitor therapy. III. CONTRAINDICATIONS None IV. WARNINGS AND PRECAUTIONS The Warnings and Precautions can be found in the Cordis EXOSEAL VCD Instructions for Use. PMA P100013: FDA Summary of Safety and Effectiveness Data {1} PMA P100013: FDA Summary of Safety and Effectiveness Data page 2 # V. DEVICE DESCRIPTION ## A. Materials and Configuration The EXOSEAL VCD consists of a Plug Applier and an absorbable Plug. The Plug Applier consists of a Handle Assembly and a Delivery Shaft (See Figure 1). The absorbable Plug is fully enclosed in the distal portion of the Delivery Shaft. The Plug Applier positions and deploys the absorbable Plug to the extravascular surface of the femoral artery access site through the existing French (F) size-specific procedural Vascular Sheath Introducer with a working length of up to 12cm without the need for a Vascular Sheath Introducer exchange before device deployment. (NOTE: The French size of the EXOSEAL VCD must correspond to the French size of the vascular sheath introducer in use: 5F, 6F or 7F). ## B. Principles of Operation for the EXOSEAL VCD System: The Delivery shaft is inserted into the existing sheath introducer and locked into position. A Bleed-Back Indicator provides visual feedback to the user that the device is correctly positioned within the vessel. A nitinol indicator wire connected to an indicator window provides feedback to the user as to the position of the Polyglycolic Acid (PGA) Plug relative to the vessel wall. When the Plug is in the correct position the Plug Deployment Button is depressed to sequentially retract the indicator wire and delivery shaft, deploying the plug extravascularly to the arteriotomy site. Light compression is applied to promote hemostasis. The PGA Plug is fully resorbed into the body within 60-90 days of implantation. # VI. ALTERNATIVE PRACTICES AND PROCEDURES Alternative practices and procedures for attaining hemostasis at the femoral artery puncture site post-catheterization include mechanical compression, manual compression, percutaneous delivery of sutures at the femoral access site, collagen-based hemostasis devices and staples. Pressure dressings and sandbags are routinely used in combination with compression methods to control oozing. {2} VII. MARKETING HISTORY The EXOSEAL VCD has been approved for sale in the following countries. The EXOSEAL VCD has not been withdrawn from marketing for any reason related to its safety or effectiveness. - Armenia - Australia - Azerbaijan - Bangladesh - Bahrain - Bosnia and Herzegovina - Chile - Colombia - Dominican Republic - El Salvador - European Union - Ghana - Guatemala - Honduras - Iran - Israel - Jamaica - Jordan - Kenya - Kuwait - Lebanon - Libya - Macedonia - Madagascar - Malaysia - Mauritius - Mongolia - Mozambique - New Zealand - Nicaragua - Nigeria - Oman - Pakistan - Palestine - Panama - Paraguay - Qatar - Saudi Arabia - Serbia and Montenegro - Singapore - South Africa - Sudan - Syria - Tanzania - Trinidad and Tobago - Turkey - Turkmenistan - United Arab Emirates - Yemen PMA P100013: FDA Summary of Safety and Effectiveness Data page 3 7 {3} PMA P100013: FDA Summary of Safety and Effectiveness Data page 4 # VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device. - Vascular injury requiring repair - Access site-related bleeding requiring transfusion - Access site-related infection - New lower extremity ischemia - Access site-related nerve injury requiring surgical repair - Retroperitoneal Bleed - Permanent access site-related nerve injury - Death - Rebleeding following initial hemostasis requiring intervention - Pseudoaneurysm - Arteriovenous fistula - Access site hematoma - Prolonged access site-related bleeding - Lower extremity arterial emboli - Transient loss of lower extremity pulse - Deep vein thrombosis - Access site-related vessel laceration - Transient access site-related nerve injury - Access site wound dehiscence - Ecchymosis - Vasovagal response - Peripheral artery total occlusion For the specific adverse events that occurred in the clinical studies, please see Section X below. # IX. SUMMARY OF PRECLINICAL STUDIES ## A. Laboratory Studies ### Engineering & Shelf Life Testing of the functionality of the device as well as its packaging has confirmed the device is protected during customary shipping, storage and handling throughout shelf-life. The data submitted support the claimed 1-year shelf-life. Functional Testing is summarized in Table 1. {4} Table 1. EXOSEAL VCD Functional Testing | Table 1 Functional Testing Summary | | | | | | --- | --- | --- | --- | --- | | Test | Acceptance Criteria | Results (t=0 / t=1 year) | | | | | | 5F | 6F | 7F | | Delivery System with Plug Testing | | | | | | Marker Band Visibility Test | Visible on the Delivery Shaft | Pass / Pass | Pass / Pass | Pass /Pass | | Sheath Insertion Test | < 2.5 lb_{f} | Not Required | Pass / Pass | Pass /Pass | | Introducer Hub Engagement Test | ≤ 15 lb_{f} | Not Required | Pass / Pass | Not Required | | Introducer Hub Disengagement Test | ≥ 1.55 lb_{f} | Not Required | Pass / Pass | Not Required | | Deployed Plug Length | ≤ 9 mm | Pass / Pass | Pass / Pass | Pass /Pass | | Plug Placement Test | Plug shall be placed 0-2 mm proximal to the intima wall | Pass / Pass | Pass / Pass | Pass /Pass | | Plunger Shaft to Plunger Disk Bond Test | ≥ 1 lb_{f} | Pass / Pass | Pass / Pass | Not Required | | Indicator Wire Lumen to PI Collar Pull Test | ≥ 1.8 lbf | Not Required | Pass / Pass | Not Required | | Plug Deployment Force Test | < 2.7 lb_{f} | Pass / Pass | Pass / Pass | Pass /Pass | | Indicator Wire to Indicator Wire End Pull Test | ≥ 0.50 lb_{f} | Not Required | Pass / Pass | Not Required | | Delivery Shaft to PI Collar Assembly Pull Test | ≥ 3.0 lb_{f} | Pass / Pass | Pass / Pass | Pass /Pass | | Indicator to Indicator Tube Bond Test | ≥ 0.50 lb_{f} | Not Required | Pass / Pass | Not Required | | Lens to Left Case Pull Test | ≥ 2 lb_{f} | Pass / Pass | Pass / Pass | Pass /Pass | | Handle Integrity Test | Handle must remain intact | Pass / Pass | Pass / Pass | Pass /Pass | | Indicator Wire Lumen Protrusion Test | ≤ 0.030" | Pass / Pass | Pass / Pass | Pass /Pass | | Marker Band Location Test | ≤ 5.06" | Pass / Pass | Pass / Pass | Pass /Pass | | Delivery Shaft Over / Under Travel Test | -0.020" ≤ Travel ≤ 0.040" | Pass / Pass | Pass / Pass | Pass /Pass | | Deployment Profile Force Test | ≤ 18.0 lb_{f} | Pass / Pass | Pass / Pass | Pass /Pass | | Trigger Lockout Force Test | > 18.0 lb_{f} | Not Required | Pass / Pass | Not Required | | Feedback System Testing | | | | | | Indicator Wire Deployment Test | Full deployment of indicator wire. | Pass / Pass | Pass / Pass | Pass /Pass | | Bleed Back Reduction Test | Bleed-back signal visibly reduced | Pass / Pass | Pass / Pass | Pass /Pass | | Indicator Wire Spring Force Test | ≥ 0.016 lb_{f} to ≤ 0.070 lb_{f} | Not Required | Pass / Pass | Not Required | | Particulates and Chemical Compatibility | | | | | | Particulate Count | • ≤ 3000 particles ≥ 10μm • ≤ 300 particles ≥ 25μm | Pass / Pass | Pass/Pass | Pass / Pass | PMA P100013: FDA Summary of Safety and Effectiveness Data {5} | Table 1 Functional Testing Summary | | | | | | --- | --- | --- | --- | --- | | Test | Acceptance Criteria | Results (t=0 / t=1 year) | | | | | | 5F | 6F | 7F | | | • ≤ 1 particle between 250μm and 650μm • no particles > 650μm. | | | | | Chemical Compatibility Test | No degradation after exposure to following solutions: • Saline Solution (0.9%) • Contrast Medium • 50 / 50 Contrast - Saline Solution | Pass/NA | Pass/NA | Pass/NA | | Packaging Testing | | | | | | Primary Package Seal Strength Test | ≥ 3.5 lb/in. | Not Required | Pass / Pass | Not Required | | Primary Package Pressurized Integrity Test | No evidence of pinholes or leaks | Not Required | Pass / Pass | Not Required | | Visual Packaging Integrity Test | Visual integrity of packaging | Not Required | Pass / Pass | Not Required | | Hang Hook Test | Visual/Hang Hook Adherence | Not Required | Pass / Pass | Not Required | | Picture IFU Securing Feature Test | Visual placement | Not Required | Pass / Pass | Not Required | | Shipper Label Adhesion / Label Integrity Test | Visual adhesion/label integrity | Not Required | Pass / Pass | Not Required | | Inner Pouch and Outer Carton Label Adhesion / Label Legibility Test | Visual adhesion/label integrity | Not Required | Pass / Pass | Not Required | | Device and Desiccant Holding Feature Test | Visual securement | Not Required | Pass / Pass | Not Required | | Desiccant Clearance Test | >1cm | Not Required | Pass / Pass | Not Required | | Barcode “Peelability” Test | Barcode label peelable | Not Required | Pass / Pass | Not Required | | Placement and Legibility of Ambulate sticker and Multilingual Patient Card Test | Visual location/legibility | Not Required | Pass / Pass | Not Required | | Legibility of Instructions for Use (IFU) Test | IFU is Legible | Not Required | Pass / Pass | Not Required | | Legibility of Picture IFU | Label is Legible | Not Required | Pass / Pass | Not Required | ## Sterilization The EXOSEAL VCD is sterilized using Electron Beam irradiation sterilization (E-Beam). The packaging system has been demonstrated to be an appropriate sterile barrier for the device and remains intact throughout shelf-life. The sterilization process has been validated to deliver a minimum Sterility Assurance Level (SAL) of $10^{-6}$ for the device and its packaging. PMA P100013: FDA Summary of Safety and Effectiveness Data {6} # Biocompatibility Biocompatibility testing of the EXOSEAL VCD was conducted in accordance with the ISO-10993 “Biological Evaluation of Medical Devices Part I: Evaluation and Testing”, to ensure that the device was biocompatible for its intended use. The components of the device were evaluated based upon patient contact (i.e., the plug- long term contact and delivery device identified patient contact elements-transient contact). As seen in Table 2 below, samples passed all testing and results concluded that the EXOSEAL VCD is non-toxic, non-sensitizing, non-irritant, non-mutagenic, non-pyrogenic and non-hemolytic. A complete list of biocompatibility tests completed for the EXOSEAL VCD is included in the following table. Table 2. EXOSEAL VCD Biocompatibility Summary | Table 2 EXOSEAL VCD Biocompatibility Summary | | | | --- | --- | --- | | Biocompatibility Test | Standard Method | Result / Specification | | Cytotoxicity | ISO 10993-5 | Pass / Non-toxic | | Maximization Sensitization | ISO 10993-10 | Pass / Non-Sensitizing | | Intracutaneous Irritation Reactivity | ISO 10993-10 | Pass / Non-irritating | | Acute Systemic Toxicity | ISO 10993-11 | Pass / No evidence of systemic toxicity | | Bacterial Mutagenicity – Ames | ISO 10993-3 | Pass / Non-mutagenic | | In-Vitro Chromosome Aberration | ISO 10993-3 | Pass / Non-clastogenic | | In Vitro Mouse Lymphome | ISO 10993-3 | Pass / Non-mutagenic | | Hemolysis | ISO 10993-4 | Pass / Non-hemolytic | | Material Mediated Pyrogenicity | ISO 10993-11 | Pass / Non-pyrogenic | | Partial Thromboplastin Time | ISO 10993-4 | Pass / Non-Activator of the intrinsic coagulation pathway. | | Platelet and Leukocyte Count | ISO 10993-4 | Pass / No significant difference in the platelet and leukocyte counts. | | Physicochemical Test | USP <661> & EP section 3.2.6 | Pass / Met the acceptance criteria for the USP & EP. | | Complement Activation (C3a & SC5b-9Assay) | ISO 10993-4 | Pass / Non-activating | | In vivo Thrombogenicity | ISO 10993-4 | Pass / Non-thrombogenic | # Evaluation of 5F EXOSEAL Vascular Closure Device (VCD) The use of the EXOSEAL VCD with a standard 5F sheath introducer was evaluated with an engineering analysis that compared the design of the 5F EXOSEAL VCD to the design of the 6F EXOSEAL VCD which was evaluated clinically. This engineering PMA P100013: FDA Summary of Safety and Effectiveness Data {7} analysis demonstrates that the design of the 5F EXOSEAL VCD is equivalent to the design of the 6F EXOSEAL VCD. ## Evaluation of EXOSEAL VCD Compatibility with 12 cm Sheath Introducer The EXOSEAL VCD was used with an 11 cm vascular sheath introducer length in the 6F ECLIPSE Trial and the 7F German and Mexican studies. However, the EXOSEAL VCD was designed to be used with a 12 cm sheath introducer length. The maximum compatible length was increased to make a wider range of sheath introducers available for use with the EXOSEAL VCD. Testing of the EXOSEAL VCD with the 12 cm length sheath introducer included both bench testing (sheath introducer compatibility and Design Verification testing) as well as simulated use testing in an animal model. Based on this testing it was determined that the EXOSEAL VCD is equally compatible with a 12 cm sheath introducer length as with an 11 cm sheath introducer length. ## B. Animal Studies A series of acute and chronic animal studies were performed to characterize the safety and effectiveness of the EXOSEAL VCD. The porcine model has previously been identified as an appropriate cardiovascular surrogate for the human subject, as such it was the primary model (rat and rabbit models were also used). Studies were conducted to evaluate the functionality of the delivery device as well as the vascular and physiologic responses to the PGA plug. The data demonstrate: - The PGA plug is well tolerated and is fully resorbed by the body within 90 days. - Compatibility with the Introducer Sheaths identified in the Instructions For Use. ## X. SUMMARY OF PIVOTAL CLINICAL STUDY The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of arterial closure with the EXOSEAL VCD intended for closure of the femoral artery following arterial access in the US under IDE G050160. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below. ### ECLIPSE TRIAL The purpose of the ECLIPSE Trial was to evaluate the safety and effectiveness of the 6F EXOSEAL VCD to facilitate hemostasis, ambulation, eligibility for hospital discharge, and hospital discharge in comparison to manual compression (MC). The study population was defined as patients undergoing cardiac or peripheral diagnostic or interventional catheterization procedures via the femoral artery approach when using a standard 6F sheath introducer with an 11 cm working length. PMA P100013: FDA Summary of Safety and Effectiveness Data {8} This was a multi-center, prospective, randomized, non-blinded controlled trial conducted at 17 sites in the United States. To be eligible, a patient was required to be at least 18 years of age and have signed an Informed Consent Form. Additionally, he or she was to be scheduled for a cardiac or peripheral diagnostic or interventional catheterization procedure utilizing a 6F arterial puncture in the common femoral artery with a target vessel lumen diameter $\geq 5\mathrm{mm}$. The primary protocol exclusions were: acute ST-elevation myocardial infarction $\leq 48$ hours prior to the catheterization procedure, prior femoral vascular surgery or vascular graft at the target site, treatment with thrombin-specific anticoagulant or low molecular weight heparin $\leq 24$ hours prior to the catheterization procedure, arterial puncture in the femoral artery of both legs, prior target artery closure with any closure devices, or closure with manual compression $\leq 30$ days prior to the catheterization procedure. Eighty-seven (87) roll-in patients and 401 randomized patients (267 6F EXOSEAL VCD and 134 MC patients in a 2:1 randomization ratio) entered the study across 17 investigative sites for a total of 488 patients. Of the 401 randomized patients, $50\%$ $(n = 200)$ were diagnostic patients and the remaining $50\%$ $(n = 201)$ were interventional patients. Among the 200 diagnostic patients, 134 patients were 6F EXOSEAL VCD patients and 66 patients were MC patients and among the 201 interventional patients, 133 were 6F EXOSEAL VCD patients and 68 patients were MC patients. Patient demographic characteristics at baseline, such as gender, age, and BMI were comparable between the two randomized groups. The majority of patients were male in both treatment groups, which is a reflection of the general referral pattern for patients undergoing diagnostic and interventional procedures. The percentages of males were similarly distributed in the 6F EXOSEAL VCD and MC treatment group of $68.2\%$ and $61.9\%$ respectively. The mean age for the 6F EXOSEAL VCD patient was $63.3 \pm 11.13$ years, and in the MC group the mean age was $61.4 \pm 10.47$ years. BMI in the 6F EXOSEAL VCD group averaged $28.9 \pm 4.99 \mathrm{~kg} / \mathrm{m}^2$ and in the MC group averaged $29.5 \pm 5.40 \mathrm{~kg} / \mathrm{m}^2$. Among the 6F ECLIPSE Trial patients, 1 diagnostic 6F EXOSEAL VCD patient, 1 diagnostic MC patient, 37 interventional 6F EXOSEAL VCD patients, and 14 interventional MC patients received GP IIb/IIIa inhibitor therapy before and/or during the catheterization procedure. The primary safety endpoint was the combined rate of major complications within $30 \pm 7$ days following the catheterization procedure. The secondary safety endpoint was the combined rate of secondary complications within $30 \pm 7$ days following the procedure. The primary effectiveness endpoints were time to hemostasis and time to ambulation. The secondary effectiveness endpoints were time to eligibility for hospital discharge, time to hospital discharge, time to device deployment, procedure success, and device success. PMA P100013: FDA Summary of Safety and Effectiveness Data page 9 13 {9} # German and Mexican Studies The purpose of the German and Mexican studies was to evaluate the safety and effectiveness of the 7F EXOSEAL VCD to facilitate hemostasis, ambulation, eligibility for hospital discharge, and hospital discharge. The study population was defined as patients undergoing cardiac or peripheral diagnostic or interventional catheterization procedures via the femoral artery approach when using a standard 7F sheath introducer with an 11 cm working length. The studies were a multi-center (German), single-center (Mexican), prospective, non-randomized, non-blinded, single treatment trials conducted at six sites in Germany and one site in Mexico. To be eligible, a patient was required to be at least 18 years of age and have signed an Informed Consent Form. Additionally, he or she was to be scheduled for a cardiac or peripheral diagnostic or interventional catheterization procedure utilizing a 7F arterial puncture in the common femoral artery with a target vessel lumen diameter ≥ 5 mm. The primary protocol exclusions were: acute ST-elevation myocardial infarction ≤ 48 hours prior to the catheterization procedure, prior femoral vascular surgery or vascular graft at the target site, treatment with thrombin-specific anticoagulant or low molecular weight heparin ≤ 24 hours prior to the catheterization procedure, arterial puncture in the femoral artery of both legs, prior target artery closure with any closure devices, or closure with manual compression ≤ 30 days prior to the catheterization procedure. The data from the German and Mexican studies were pooled and compared to the manual compression control group data (134 MC patients) from the 6F ECLIPSE Trial. Patient demographic characteristics at baseline, such as gender, age, and BMI were comparable between the German and Mexican studies. Thirty-Five (35) roll-in patients and 88 study patients entered the study across seven investigative sites for a total of 123 patients. Of the 88 study patients, 49% (n=43) were diagnostic patients and the remaining 51% (n=45) were interventional patients. Patient demographic characteristics for gender and age were comparable between the 7F EXOSEAL VCD pooled studies and the 6F MC control group, while BMI was lower in the 7F EXOSEAL VCD pooled studies. The percentages of males were similarly distributed in the 7F EXOSEAL VCD pooled studies and 6F MC control group of 71.6% and 61.9% respectively. The mean age in the 7F EXOSEAL VCD pooled studies was 62.7 ± 10.85 years, and in the 6F MC group the mean age was 61.4 ± 10.47 years. BMI in the 7F EXOSEAL VCD pooled studies averaged 27.9 ± 3.77 kg/m² and in the MC group averaged 29.5 ± 5.40 kg/m². The primary safety endpoint was the combined rate of major complications within 30 ± 7 days following the catheterization procedure. The secondary safety endpoint was the combined rate of secondary complications within 30 ± 7 days following the catheterization procedure. The primary effectiveness endpoints were time to hemostasis and time to ambulation. The secondary effectiveness endpoints were time to eligibility PMA P100013: FDA Summary of Safety and Effectiveness Data page 10 {10} for hospital discharge, time to hospital discharge, time to device deployment, procedure success, and device success. ## Key Inclusion Criteria for Clinical Studies 1. Patient is between 18 and 85 years of age, inclusive; 2. Patient/guardian provides written informed consent; 3. Patient is scheduled for a coronary or peripheral diagnostic or interventional procedure; 4. Patient is able to undergo emergent vascular surgery if a complication related to the VCD necessitates such surgery; 5. Patient has a 6F arterial puncture located in the common femoral artery; 6. Target vessel has a lumen diameter $\geq 5\mathrm{mm}$; and 7. Patient is willing and able to complete follow-up. ## Key Exclusion Criteria for Clinical Studies 1. Acute ST-elevation myocardial infarction $\leq 48$ hours prior to the cardiac or peripheral catheterization procedure; 2. Uncontrolled hypertension at time of closure $(\mathrm{BP} \geq 180 / 110 \mathrm{mmHg})$; 3. Patients who bruise or bleed easily or with a history of significant bleeding or platelet disorders, such as Thrombocytopenia (with $< 100,000$ platelet count) Von Willebrand's disease, anemia $(\mathrm{Hgb} < 10 \mathrm{g/dL}, \mathrm{Hct} < 30\%)$, thrombasthenia, decreased fibrinogen $(< 200 \mathrm{mg/dL})$, and Factor V deficiency; 4. Prior femoral vascular surgery or vascular graft in region of access site; 5. Pre-existing systemic or cutaneous infection; 6. Pre-existing severe non-cardiac systemic disease or pre-existing terminal illness; 7. Patient has known allergy to any materials used in the VCD; 8. Patient is known or suspected to be pregnant, or is lactating; 9. Thrombolytic therapy (e.g. streptokinase, urokinase, t-PA) $\leq 24$ hours prior to the cardiac or peripheral catheterization procedure; 10. Angiomax (bivalirudin) or other thrombin-specific anticoagulants or low molecular weight heparin $\leq 24$ hours prior to the cardiac or peripheral catheterization procedure; 11. $\mathrm{BMI} > 40 \mathrm{kg/m^2}$; 12. Symptomatic leg ischemia in the target vessel limb including severe claudication (< 100 feet) or weak/absent pulse; 13. Planned arterial access at the same access site $\leq 30$ days following the femoral artery closure procedure; 14. Patient is known to require an extended hospitalization (e.g. patient is undergoing CABG surgery); 15. Arterial puncture in the femoral artery of both legs; 16. Prior target artery closure with any closure device, or closure with manual compression $\leq 30$ days prior to the cardiac or peripheral catheterization procedure; 17. Prior or recent use of an intra-aortic balloon pump through the arterial access site; PMA P100013: FDA Summary of Safety and Effectiveness Data {11} 18. Patient is ineligible for in-lab catheterization lab introducer sheath removal; 19. Evidence of a preexisting hematoma, arteriovenous fistula, or pseudoaneurysm at the access site prior to start of femoral artery closure procedure; 20. The targeted femoral artery is tortuous or requires an introducer sheath length > 11 cm; 21. Fluoroscopically visible calcium, atherosclerotic disease, or stent ≤ 1 cm of the puncture site that would interfere with the placement of the VCD's plug; 22. Targeted femoral artery diameter stenosis ≥ 50%; 23. Difficulty in obtaining vascular access resulting in multiple arterial punctures and/or posterior arterial puncture; 24. Antegrade puncture; 25. Heparinized patient with elevated pre-closure ACT level: Vascular Closure Device: > 250 seconds with GP IIb/IIIa inhibitor > 300 seconds no GP IIb/IIIa inhibitor Manual Compression: > 180 seconds; 26. Cardiogenic shock (hemodynamic instability requiring intravenous medications or mechanical support) experienced during or immediately post-catheterization; 27. Concurrent participation in another investigational device or drug trial; 28. Patient is unable to ambulate at baseline; 29. Patient has already participated in this trial; 30. Patient is unavailable for follow-up; and 31. Any angiographic or clinical evidence that the investigator feels would place the patient at increased risk with the use of the VCD. The exclusion criteria for the 7F German and Mexican studies were identical to that for the 6F ECLIPSE Trial except for the following 2 exclusion criteria in the 7F studies, which varied from the corresponding exclusion criteria for the 6F ECLIPSE Trial: - Heparinized patients with elevated pre-closure ACT level: > 250 seconds with GP IIb/IIIa inhibitor > 300 seconds no GP IIb/IIIa inhibitor; - Symptomatic leg ischemia in the target vessel limb including severe claudication (< 50 meter) or weak/absent pulse. The 7F German and Mexican studies also included two additional exclusion criteria not listed in the 6F ECLIPSE Trial: 32. Patient has known allergy to contrast medium; and 33. Required simultaneous ipsilateral or contralateral venous puncture. PMA P100013: FDA Summary of Safety and Effectiveness Data {12} # Safety Results from ECLIPSE Trial and German and Mexican Studies The 6F EXOSEAL VCD was evaluated in a prospective, multi-center, randomized (2:1) clinical trial (the ECLIPSE Trial) in the United States comparing the 6F EXOSEAL VCD to Manual Compression (MC) and involving 401 total patients undergoing diagnostic angiography (n=200) or interventional procedures (n=201). The 7F EXOSEAL VCD was evaluated in 2 small, non-randomized clinical studies, which were a multi-center study in Germany and a single-center study in Mexico, whose data were pooled and compared to the MC control group from the 6F ECLIPSE Trial. The pooled German/Mexican 7F VCD data were from 88 total patients undergoing diagnostic angiography (n = 43) or interventional procedures (n = 45). Tables 3-5 show the major and secondary complications data for the 6F ECLIPSE Trial and for the 7F VCD group versus 6F MC group comparison. Table 3 Safety Results - All Patients (ITT) Treated | Description of Event (Event Based) | 6F ECLIPSE Trial | | | | | Pooled 7F VCD Data Compared to 6F MC Data | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | VCD (n=267patients) | MC (n=134patients) | Difference VCD-MC¹ | Upper Bound² | P-Values³ | Pooled 7F VCD (n=88 patients) | Difference VCD-MC⁴ | Upper Bound⁵ | P-values⁶ | | Major Adverse Events (Combined Event Rate) at 30-days | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | 0.0006 | 0/88 (0.00%) | 0.00% | 3.35% | 0.0276 | | Vascular Repair | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | 0.0006 | 0/88 (0.00%) | 0.00% | 3.35% | 0.0276 | | Access site-related bleeding requiring transfusion | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | 0.0006 | 0/88 (0.00%) | 0.00% | 3.35% | 0.0276 | | Access site-related infection requiring treatment | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | 0.0006 | 0/88 (0.00%) | 0.00% | 3.35% | 0.0276 | | Any new documented ipsilateral lower extremity ischemia | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | 0.0006 | 0/88 (0.00%) | 0.00% | 3.35% | 0.0276 | | Surgery for access site-related nerve injury | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | 0.0006 | 0/88 (0.00%) | 0.00% | 3.35% | 0.0276 | | Permanent(>30 days) access site-related nerve injury | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | 0.0006 | 0/88 (0.00%) | 0.00% | 3.35% | 0.0276 | | Secondary Adverse Events (Combined Event Rate) at 30-days | 24/267 (8.99%) | 6/134 (4.48%) | 4.51% | 8.66% | - | 3/88 (3.41%) | -1.07% | 4.18% | - | | Rebleeding Following Initial Hemostasis | 14/267 (5.24%) | 3/134 (2.24%) | 3.00% | 6.17% | - | 0/88 (0.00%) | -2.24% | 0.70% | - | | Pseudoaneurysm not Requiring Treatment | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Treated Pseudoaneurysm | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Documented Arteriovenous Fistula | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Access Site Hematoma >= 6cm | 6/267 (2.25) | 1/134 (0.75%) | 1.50% | 3.72% | - | 3/88 (3.41%) | 2.66% | 7.47% | - | | Access Site-Related Bleeding Requiring > 30 min for Hemostasis | 1/267 (0.37) | 1/134 (0.75%) | -0.37% | 1.16% | - | 0/88 (0.00%) | -0.75% | 2.20% | - | | Post-Hospital Discharge Access Site-Related Bleeding | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Ipsilateral Lower Extremity Arterial Emboli | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Transient Loss of Ipsilateral Lower Extremity Pulse | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Ipsilateral Deep Vein Thrombosis | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Access Site-Related Vessel Laceration | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Transient Access Site-Related Nerve Injury | 1/267 (0.37) | 0/134 (0.00) | 0.37% | 1.81% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Access Site Wound Dehiscence | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Treated, Localized Access Site Infection | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Retroperitoneal Bleeding | 2/267 (0.75) | 0/134 (0.00) | 0.75% | 2.34% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Ipsilateral Peripheral Artery Total Occlusion | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Echymosis >= 6cm | 0/267 (0.00) | 1/134 (0.75%) | -0.75% | 0.43% | - | 0/88 (0.00%) | -0.75% | 2.20% | - | | Intraluminal Plug Delivery Not Requiring Surgical Intervention | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Decrease in Pedal Pulse | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | | Death | 0/267 (0.00) | 0/134 (0.00) | 0.00% | 1.14% | - | 0/88 (0.00%) | 0.00% | 3.35% | - | Numbers are % (counts/sample size) ¹ Proportion differences between 6F VCD group and 6F MC group (PₕCD - PMC) PMA P100013: FDA Summary of Safety and Effectiveness Data {13} One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between 6F VCD group and 6F MC group (P_{VCD} - P_{MC}). It was calculated using unconditional exact method P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (6F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. Proportion differences between pooled 7F VCD group and 6F MC group (P_{VCD} - P_{MC}) One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between pooled 7F VCD group and 6F MC group (P_{VCD} - P_{MC}). It was calculated using unconditional exact method P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (7F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. Table 4 Safety Results – Diagnostic ITT Patients | Description of Event (Event Based) | 6F ECLIPSE Trial | | | | | Pooled 7F VCD Data Compared to 6F MC Data | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | VCD (n=134patients) | MC (n=66patients) | Difference VCD-MC¹ | Upper Bound² | P-Values³ | Pooled 7F VCD (n=43 patients) | Difference VCD-MC⁴ | Upper Bound⁵ | P-values⁶ | | Major Adverse Events (Combined Event Rate) at 30-days | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | 0.0129 | 0/43 (0.00%) | 0.00% | 6.73% | 0.1728 | | Vascular Repair | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | 0.0129 | 0/43 (0.00%) | 0.00% | 6.73% | 0.1728 | | Access site-related bleeding requiring transfusion | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | 0.0129 | 0/43 (0.00%) | 0.00% | 6.73% | 0.1728 | | Access site-related infection requiring treatment | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | 0.0129 | 0/43 (0.00%) | 0.00% | 6.73% | 0.1728 | | Any new documented ipsilateral lower extremity ischemia | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | 0.0129 | 0/43 (0.00%) | 0.00% | 6.73% | 0.1728 | | Surgery for access site-related nerve injury | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | 0.0129 | 0/43 (0.00%) | 0.00% | 6.73% | 0.1728 | | Permanent(>30 days) access site-related nerve injury | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | 0.0129 | 0/43 (0.00%) | 0.00% | 6.73% | 0.1728 | | Secondary Adverse Events (Combined Event Rate) at 30-days | 4/134 (2.99) | 1/66 (1.52) | 1.47% | 5.42% | - | 1/43 (2.33%) | 0.81% | 8.55% | - | | Rebleeding Following Initial Hemostasis | 2/134 (1.49) | 1/66 (1.52) | -0.02% | 3.46% | - | 0/43 (0.00%) | -1.52% | 4.78% | - | | Pseudoaneurysm not Requiring Treatment | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Treated Pseudoaneurysm | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Documented Arteriovenous Fistula | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Access Site Hematoma >= 6cm | 1/134 (0.75) | 0/66 (0.00) | 0.75% | 3.55% | - | 1/43 (2.33%) | 2.33% | 10.56% | - | | Access Site-Related Bleeding Requiring > 30 min for Hemostasis | 1/134 (0.75) | 0/66 (0.00) | 0.75% | 3.55% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Post-Hospital Discharge Access Site-Related Bleeding | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Ipsilateral Lower Extremity Arterial Emboli | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Transient Loss of Ipsilateral Lower Extremity Pulse | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Ipsilateral Deep Vein Thrombosis | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Access Site-Related Vessel Laceration | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Transient Access Site-Related Nerve Injury | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Access Site Wound Dehiscence | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Treated, Localized Access Site Infection | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Retroperitoneal Bleeding | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Ipsilateral Peripheral Artery Total Occlusion | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Echymosis >= 6cm | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Intraluminal Plug Delivery Not Requiring Surgical Intervention | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Decrease in Pedal Pulse | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | | Death | 0/134 (0.00) | 0/66 (0.00) | 0.00% | 2.34% | - | 0/43 (0.00%) | 0.00% | 6.73% | - | Numbers are % (counts/sample size) ¹ Proportion differences between 6F VCD group and 6F MC group (P_{VCD} - P_{MC}) ² One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between 6F VCD group and 6F MC group (P_{VCD} - P_{MC}). It was calculated using unconditional exact method ³ P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (6F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. ⁴ Proportion differences between pooled 7F VCD group and 6F MC group (P_{VCD} - P_{MC}) ⁵ One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between pooled 7F VCD group and 6F MC group (P_{VCD} - P_{MC}). It was calculated using unconditional exact method ⁶ P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (7F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. PMA P100013: FDA Summary of Safety and Effectiveness Data {14} Table 5 Safety Results – Interventional ITT Patients | Description of Event (Event Based) | 6F ECLIPSE Trial | | | | | Pooled 7F VCD Data Compared to 6F MC Data | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | VCD (n=133 patients) | MC (n=68 patients) | Difference VCD-MC¹ | Upper Bound² | P-Values³ | Pooled 7F VCD (n=45 patients) | Difference VCD-MC⁴ | Upper Bound⁵ | P-values⁶ | | Major Adverse Events (Combined Event Rate) at 30-days | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | 0.0119 | 0/45 (0.00%) | 0.00% | 6.44% | 0.1593 | | Vascular Repair | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | 0.0119 | 0/45 (0.00%) | 0.00% | 6.44% | 0.1593 | | Access site-related bleeding requiring transfusion | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | 0.0119 | 0/45 (0.00%) | 0.00% | 6.44% | 0.1593 | | Access site-related infection requiring treatment | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | 0.0119 | 0/45 (0.00%) | 0.00% | 6.44% | 0.1593 | | Any new documented ipsilateral lower extremity ischemia | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | 0.0119 | 0/45 (0.00%) | 0.00% | 6.44% | 0.1593 | | Surgery for access site-related nerve injury | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | 0.0119 | 0/45 (0.00%) | 0.00% | 6.44% | 0.1593 | | Permanent(>30 days) access site-related nerve injury | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | 0.0119 | 0/45 (0.00%) | 0.00% | 6.44% | 0.1593 | | Secondary Adverse Events (Combined Event Rate) at 30-days | 20/133 (15.04%) | 5/68 (7.35) | 7.68% | 14.93% | - | 2/45 (4.44%) | -2.91% | 6.44% | - | | Rebleeding Following Initial Hemostasis | 12/133 (9.02%) | 2/68 (2.94) | 6.08% | 11.75% | - | 0/45 (0.00%) | -2.94% | 3.04% | - | | Pseudoaneurysm not Requiring Treatment | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Treated Pseudoaneurysm | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Documented Arteriovenous Fistula | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Access Site Hemaloma >= 6cm | 5/133 (3.76) | 1/68 (1.47) | 2.29% | 6.47% | - | 2/45 (4.44%) | 2.97% | 11.29% | - | | Access Site-Related Bleeding Requiring > 30 min for Hemostasis | 0/133 (0.00) | 1/68 (1.47) | -1.47% | 0.87% | - | 0/45 (0.00%) | -1.47% | 4.38% | - | | Post-Hospital Discharge Access Site-Related Bleeding | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Ipsilateral Lower Extremity Arterial Emboli | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Transient Loss of Ipsilateral Lower Extremity Pulse | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Ipsilateral Deep Vein Thrombosis | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Access Site-Related Vessel Laceration | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Transient Access Site-Related Nerve Injury | 1/133 (0.75) | 0/68 (0.00) | 0.75% | 3.61% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Access Site Wound Dehiscence | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Treated, Localized Access Site Infection | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Retroperitoneal Bleeding | 2/133 (1.50) | 0/68 (0.00) | 1.50% | 4.67% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Ipsilateral Peripheral Artery Total Occlusion | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Ecchymosis >= 6cm | 0/133 (0.00) | 1/68 (1.47) | -1.47% | 0.87% | - | 0/45 (0.00%) | -1.47% | 4.38% | - | | Intraluminal Plug Delivery Not Requiring Surgical Intervention | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Decrease in Pedal Pulse | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | | Death | 0/133 (0.00) | 0/68 (0.00) | 0.00% | 2.23% | - | 0/45 (0.00%) | 0.00% | 6.44% | - | Numbers are % (counts/sample size) ¹ Proportion differences between 6F VCD group and 6F MC group (Pₕᵢₙᵃ - Pₘₛₓ) ² One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between 6F VCD group and 6F MC group (Pₕᵢₙᵃ - Pₘₛₓ). It was calculated using unconditional exact method ³ P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (6F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. ⁴ Proportion differences between pooled 7F VCD group and 6F MC group (Pₕᵢₙᵃ - Pₘₛₓ) ⁵ One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between pooled 7F VCD group and 6F MC group (Pₕᵢₙᵃ - Pₘₛₓ). It was calculated using unconditional exact method ⁶ P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (7F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. Among the 6F ECLIPSE Trial patients, 1 diagnostic VCD patient, 1 diagnostic MC patient, 37 interventional VCD patients, and 14 interventional MC patients received GP IIb/IIIa inhibitor therapy before and/or during the catheterization procedure. Table 6 shows the major and secondary complication data for the interventional patients receiving GP IIb/IIIa inhibitor therapy in the 6F ECLIPSE Trial. PMA P100013: FDA Summary of Safety and Effectiveness Data {15} Table 6 Safety Results – Interventional ITT Patients who have received GP IIb/IIIa inhibitor in 6F ECLIPSE Trial | Description of Event (Event Based) | 6F VCD (n=37 patients) | 6F MC (n=14 patients) | Difference VCD-MC¹ | Upper Bound² | P-values³ | | --- | --- | --- | --- | --- | --- | | Major Adverse Events (Combined Event Rate) at 30-days | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | 0.2208 | | Vascular Repair | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | 0.2208 | | Access site-related bleeding requiring transfusion | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | 0.2208 | | Access site-related infection requiring treatment | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | 0.2208 | | Any new documented ipsilateral lower extremity ischemia | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | 0.2208 | | Surgery for access site-related nerve injury | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | 0.2208 | | Permanent(>30 days) access site-related nerve injury | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | 0.2208 | | Secondary Adverse Events (Combined Event Rate) at 30-days | 4/37 (10.81%) | 2/14 (14.29%) | -3.47% | 12.76% | - | | Rebleeding Following Initial Hemostasis | 2/37 (5.41%) | 0/14 (0.00%) | 5.41% | 16.05% | - | | Pseudoaneurysm not Requiring Treatment | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Treated Pseudoaneurysm | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Documented Arteriovenous Fistula | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Access Site Hematoma >= 6cm | 0/37 (0.00%) | 1/14 (7.14%) | -7.14% | 2.36% | - | | Access Site-Related Bleeding Requiring > 30 min for Hemostasis | 0/37 (0.00%) | 1/14 (7.14%) | -7.14% | 2.36% | - | | Post-Hospital Discharge Access Site-Related Bleeding | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Ipsilateral Lower Extremity Arterial Emboli | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Transient Loss of Ipsilateral Lower Extremity Pulse | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Ipsilateral Deep Vein Thrombosis | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Access Site-Related Vessel Laceration | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Transient Access Site-Related Nerve Injury | 1/37 (2.70%) | 0/14 (0.00%) | 2.70% | 12.48% | - | | Access Site Wound Dehiscence | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Treated, Localized Access Site Infection | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Retroperitoneal Bleeding | 1/37 (2.70%) | 0/14 (0.00%) | 2.70% | 12.48% | - | | Ipsilateral Peripheral Artery Total Occlusion | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Ecohymosis >= 6cm | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Intraluminal Plug Delivery Not Requiring Surgical Intervention | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Decrease in Pedal Pulse | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | | Death | 0/37 (0.00%) | 0/14 (0.00%) | 0.00% | 7.83% | - | Numbers are % (counts/sample size) ¹ Proportion differences between 6F VCD group and 6F MC group (PₕCD - PₘC). ² One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between 6F VCD group and 6F MC group (PₕCD - PₘC). It was calculated using unconditional exact method ³ P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (6F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. ## Effectiveness Results from ECLIPSE Trial and German and Mexican Studies All 401 enrolled subjects in the ECLIPSE Trial were evaluable for effectiveness. Time to hemostasis was defined as time from when the introducer sheath was removed to the time that hemostasis (no or minimal subcutaneous oozing and the absence of expanding or developing hematoma) was achieved. Hemostasis was achieved in significantly less time with the 6F EXOSEAL VCD device as compared to manual compression. The mean time to hemostasis was 4.38 ± 11.59 minutes compared with 20.05 ± 22.54 minutes for 6F EXOSEAL VCD and MC respectively, with the -15.68 minute difference 95% CI: [-19.04, -12.31] P<0.0001. PMA P100013: FDA Summary of Safety and Effectiveness Data {16} Time to ambulation was defined as the time from when the introducer sheath was removed to the time when ambulation was achieved (patient standing and walking at least 20 feet without rebleeding). Time to ambulation was also significantly favorable to the 6F EXOSEAL VCD group over MC with a mean time to ambulation of $2.54 \pm 5.02$ hours compared with $6.24 \pm 13.34$ hours in the MC group, with the -3.70 hour difference $95\%$ CI: [-5.53, -1.87] $P = 0.0028$. All 88 study subjects in the German and Mexican Studies were evaluable for effectiveness. Time to hemostasis and time to ambulation were defined the same as in the ECLIPSE Trial. Hemostasis was achieved in significantly less time with the 7F EXOSEAL VCD device as compared to manual compression. The mean time to hemostasis was $3.25 \pm 4.25$ minutes compared with $20.05 \pm 22.54$ minutes for 7F EXOSEAL VCD and MC respectively, with the $-16.80$ minute difference $95\%$ CI: $[-21.60, -12.01]$ $P < 0.0001$. Time to ambulation was also significantly favorable to the 7F EXOSEAL VCD group over MC with a mean time to ambulation of $2.64 \pm 5.43$ hours compared with $6.24 \pm 13.34$ hours in the MC group, with the -3.60 hour difference $95\%$ CI: [-6.56, -0.64] $P = 0.0066$. Tables 7 and 8 show the primary and secondary effectiveness results for the 6F ECLIPSE Trial and for the 7F EXOSEAL VCD group versus 6F MC group comparison. Table 7 Primary Effectiveness Results – All Patients (ITT) Treated | Primary Effective Endpoints | 6F ECLIPSE Trial | | | Pooled 7F VCD Data Compared to 6F MC Data | | | --- | --- | --- | --- | --- | --- | | | 6F VCD | 6F MC | P-value(a) | Pooled 7F VCD | P-value(b) | | ITT Patients | N=267 | N=134 | | N=88 | | | Time to Hemostasis (min) | | | | | | | Mean ± STD (N) | 4.38±11.59(267) | 20.05±22.54(131) | <0.0001 | 3.25 ±4.25 (88) | <0.0001 | | Median, Range (Min, Max) | 2.0 (2.0, 175.0) | 15.0 (3.0, 220.0) | | 2.0 (2.0, 35.0) | | | Time to Ambulation (hr) | | | | | | | Mean ± STD (N) | 2.54±5.02(264) | 6.24±13.34(129) | 0.0028 | 2.64 ±5.43 (88) | 0.0066 | | Median, Range (Min, Max) | 1.2 (0.9, 69.1) | 4.3 (1.3, 152.2) | | 1.1 (0.01, 24.3) | | | Diagnostic ITT Patients | N=134 | N=66 | | N=43 | | | Time to Hemostasis (min) | | | | | | | Mean ± STD (N) | 3.34±4.86(134) | 14.80±5.85(65) | <0.0001 | 2.86 ±2.77 (43) | <0.0001 | | Median, Range (Min, Max) | 2.0 (2.0, 34.0) | 15.0 (3.0, 30.0) | | 2.0 (2.0, 15.0) | | | Time to Ambulation (hr) | | | | | | | Mean ± STD (N) | 1.59±1.22(133) | 6.63±18.40(66) | 0.0295 | 2.15 ±4.90 (43) | 0.0637 | | Median, Range (Min, Max) | 1.1 (0.9, 8.4) | 4.1 (1.3, 152.2) | | 1.1, (0.01, 24.2) | | | Interventional ITT Patients | N=133 | N=68 | | N=45 | | | Time to Hemostasis (min) | | | | | | | Mean ± STD (N) | 5.43±15.64(133) | 25.23±30.45(66) | <0.0001 | 3.62 ±5.31 (45) | <0.0001 | | Median, Range (Min, Max) | 2.0 (2.0, 175.0) | 20.0 (10.0, 220.0) | | 2.0 (2.0, 35.0) | | | Time to Ambulation (hr) | | | | | | | Mean ± STD (N) | 3.51±6.90(131) | 5.83±3.52(63) | 0.0022 | 3.11 ±5.90 (45) | 0.0074 | | Median, Range (Min, Max) | 2.0 (0.9, 69.1) | 4.8 (2.8, 21.8) | | 1.1, (1.0, 24.3) | | PMA P100013: FDA Summary of Safety and Effectiveness Data {17} Numbers are Mean ± STD (Sample Size). Numbers of patients for the summary of continuous measures are based on number of non-missing values. (a) P-values were calculated using unpaired t-test of inequality in mean differences of the continuous outcomes between 6F VCD and 6F MC group (b) P-values were calculated using unpaired t-test of inequality in mean differences of the continuous outcomes between pooled 7F VCD and 6F MC group Table 8 Secondary Effectiveness Results – All Patients (ITT) Treated | Secondary Effectiveness Endpoints | 6F ECLIPSE Trial | | | Pooled 7F VCD Data Compared to 6F MC Data | | | --- | --- | --- | --- | --- | --- | | | 6F VCD | 6F MC | P-value(a) | Pooled 7F VCD | P-value(b) | | ITT Patients | N=267 | N=134 | | N=88 | | | Time to Eligibility for Hospital Discharge (hr) | | | | | | | Mean ± STD (N) | 12.57±13.91 (257) | 16.26±27.49 (128) | 0.1540 | 12.54±23.85 (75) | 0.3301 | | Median, Range (Min, Max) | 5.0 (0.6, 116.1) | 14.1 (0.0, 283.7) | | 6.9 (1.1, 190.7) | | | Time to Actual Hospital Discharge (hr) | | | | | | | Mean ± STD (N) | 16.77±19.79 (264) | 19.35±29.23 (133) | 0.3612 | 33.22±45.90 (73) | 0.0214 | | Median, Range (Min, Max) | 17.9 (1.1, 196.1) | 18.4 (3.0, 285.4) | | 22.6 (1.5, 288.7) | | | Time for Device Deployment (min) | | | | | | | Mean ± STD (N) | 1.01±2.12 (260) | - | - | 0.62 ±0.25 (88) | - | | Median, Range (Min, Max) | 0.7 (0.0, 23.3) | | | 0.6 (0.2, 1.4) | | | Procedure Success | 245/267 (91.8%) | 122/134 (91.0%) | 0.8500 | 83 /88 (94.3%) | 0.4462 | | Device Success | 238/267 (89.1%) | - | - | 82 /88 (93.2%) | - | | Diagnostic ITT Patients | N=134 | N=66 | | N=43 | | | Time to Eligibility for Hospital Discharge (hr) | | | | | | | Mean ± STD (N) | 4.94±7.41(131) | 11.88±35.40(64) | 0.1257 | 7.00 ±6.98 (37) | 0.2894 | | Median, Range (Min, Max) | 2.1 (0.6, 47.0) | 4.4 (0.4, 283.7) | | 6.3 (1.1, 28.4) | | | Time to Actual Hospital Discharge (hr) | | | | | | | Mean ± STD (N) | 8.72±20.15(132) | 14.78±38.79(65) | 0.2402 | 17.49±25.33 (35) | 0.6749 | | Median, Range (Min, Max) | 3.0 (1.1, 196.1) | 5.2 (3.0, 285.4) | | 8.9 (1.5, 142.8) | | | Time for Device Deployment (min) | | | | | | | Mean ± STD (N) | 1.19±2.87(131) | - | - | 0.62 ±0.23 (43) | - | | Median, Range (Min, Max) | 0.7 (0.0, 23.3) | | | 0.6 (0.2, 1.4) | | | Procedure Success | 126/134 (94.0%) | 65/66 (98.5%) | 0.2763 | 41 /43 (95.3%) | 0.5606 | | Device Success | 125/134 (93.3%) | - | - | 41 /43 (95.3%) | - | | Interventional ITT Patients | N=133 | N=68 | | N=45 | | | Time to Eligibility for Hospital Discharge (hr) | | | | | | | Mean ± STD (N) | 20.49±14.67(126) | 20.64±15.22(64) | 0.9460 | 17.94±32.09 (38) | 0.6273 | | Median, Range (Min, Max) | 21.3 (1.0,116.1) | 19.0 (0.0, 119.0) | | 7.2 (1.3, 190.7) | | | Time to Actual Hospital Discharge (hr) | | | | | | | Mean ± STD (N) | 24.83±15.80(132) | 23.71±14.35(68) | 0.6270 | 47.71±55.32 (38) | 0.0122 | | Median, Range (Min, Max) | 23.2 (1.5, 119.3) | 20.9 (4.6, 119.0) | | 24.3 (13.1, 288.7) | | | Time for Device Deployment (min) | | | | | | | Mean ± STD (N) | 0.82±0.83(129) | - | - | 0.61 ±0.26 (45) | - | | Median, Range (Min, Max) | 0.7 (0.0, 7.0) | | | 0.6 (0.3, 1.3) | | | Procedure Success | 119/133(89.5%) | 57/68(83.8%) | 0.2651 | 42 /45 (93.3%) | 0.1565 | | Device Success | 113/133(85.0%) | - | - | 41 /45 (91.1%) | - | Numbers are Mean ± STD (Sample Size). Numbers of patients for the summary of continuous measures are based on number of non-missing values. (a) P-values were calculated using unpaired t-test of inequality in mean differences of the continuous outcomes between 6F VCD and 6F MC group (b) P-values were calculated using unpaired t-test of inequality in mean differences of the continuous outcomes between pooled 7F VCD and 6F MC group Table 9 shows the cumulative times to hemostasis, ambulation, eligibility for hospital discharge, and actual hospital discharge for the total patients in the 6F ECLIPSE Trial. PMA P100013: FDA Summary of Safety and Effectiveness Data {18} Table 9 Effectiveness Results by Post-Procedure Time Interval for ITT Patients | Variable | 6F ECLIPSE Trial | | Pooled 7F VCD Data | | --- | --- | --- | --- | | | VCD (n=267 patients) | MC (n=134 patients) | Pooled 7F VCD (n=88 patients) | | Time to Hemostasis (min) | | | | | Mean ± STD (n) | 4.38±11.59 (267) | 20.05±22.54 (131) | 3.25±4.25 (88) | | Median | 2.00 | 15.00 | 2.00 | | Range (Min, Max) | 2.00, 175.0 | 3.00, 220.0 | 2.00, 35.00 | | Distribution | Cumulative n (%) | Cumulative n (%) | Cumulative n(%) | | ≤ 2 min | 69.7% (186/267) | 0.0% (0/131) | 71.6% (63/88) | | ≤ 5 min | 89.5% (239/267) | 2.3% (3/131) | 93.2% (82/88) | | ≤ 10 min | 92.9% (248/267) | 25.2% (33/131) | 95.5% (84/88) | | ≤ 20 min | 97.0% (259/267) | 80.2% (105/131) | 98.9% (87/88) | | ≤ 30 min | 99.3% (265/267) | 96.2% (126/131) | 98.9% (87/88) | | Time to Ambulation (hour) | | | | | Mean ± STD (n) | 2.54±5.02 (264) | 6.24±13.34(129) | 2.64±5.43 (88) | | Median | 1.21 | 4.30 | 1.07 | | Range (Min, Max) | 0.88, 69.09 | 1.33, 152.2 | 0.01, 24.32 | | Distribution | Cumulative n (%) | Cumulative n (%) | Cumulative n(%) | | ≤ 1 hour | 3.8% (10/264) | 0.0% (0/129) | 11.4% (10/88) | | ≤ 2 hours | 68.2% (180/264) | 0.8% (1/129) | 89.8% (79/88) | | ≤ 5 hours | 91.3% (241/264) | 66.7% (86/129) | 92.0% (81/88) | | ≤ 7 hours | 95.1% (251/264) | 93.0% (120/129) | 92.0% (81/88) | | ≤ 10 hours | 97.3% (257/264) | 94.6% (122/129) | 93.2% (82/88) | | ≤ 15 hours | 98.1% (259/264) | 96.9% (125/129) | 93.2% (82/88) | | Time to Eligible Discharge (Hour) | | | | | Mean ± STD (n) | 12.57±13.91 (257) | 16.26±27.49 (128) | 12.54±23.85 (75) | | Median | 5.03 | 14.08 | 6.94 | | Range (Min, Max) | 0.56, 116.1 | 0.00, 283.7 | 1.08, 190.73 | | Distribution | Cumulative n (%) | Cumulative n (%) | Cumulative n(%) | | ≤ 2 hour | 22.2% (57/257) | 2.3% (3/128) | 16.0% (12/75) | | ≤ 4 hours | 46.7% (120/257) | 18.0% (23/128) | 30.7% (23/75) | | ≤ 8 hours | 54.5% (140/257) | 45.3% (58/128) | 72.0% (54/75) | | ≤ 12 hours | 54.9% (141/257) | 46.9% (60/128) | 72.0% (54/75) | | ≤ 24 hours | 86.4% (222/257) | 93.8% (120/128) | 93.3% (70/75) | | ≤ 48 hours | 98.8% (254/257) | 98.4% (126/128) | 97.3% (73/75) | | Time to Actual Discharge (Hour) | | | | | Mean ± STD (n) | 16.77±19.79 (264) | 19.35±29.23 (133) | 33.22±45.90 (73) | | Median | 17.93 | 18.36 | 22.63 | | Range (Min, Max) | 1.11, 196.1 | 2.98, 285.4 | 1.47, 288.70 | | Distribution | Cumulative n (%) | Cumulative n (%) | Cumulative n(%) | | ≤ 2 hour | 10.2% (27/264) | 0.0% (0/133) | 2.7% (2/73) | | ≤ 4 hours | 34.5% (91/264) | 9.0% (12/133) | 12.3% (9/73) | | ≤ 8 hours | 45.8% (121/264) | 39.9% (53/133) | 19.2% (14/73) | | ≤ 12 hours | 47.0% (124/264) | 40.6% (54/133) | 28.8% (21/73) | | ≤ 24 hours | 75.4% (199/264) | 85.0% (113/133) | 60.3% (44/73) | | ≤ 48 hours | 97.0% (256/264) | 97.7% (130/133) | 82.2% (60/73) | Denominators for percentage calculations are based on number of non-missing responses. Numbers of patients for the summary of continuous measures are based on number of non-missing values. PMA P100013: FDA Summary of Safety and Effectiveness Data {19} The primary and secondary effectiveness results for the interventional patients in the 6F ECLIPSE Trial who received GP IIb/IIIa inhibitor therapy are shown in Table 10. Table 10 Effectiveness Results – Interventional ITT Patients who have Received GP IIb/IIIa inhibitor in 6F ECLIPSE Trial | Effectiveness Measures | VCD (n=37 patients) | MC (n=14 patients) | Difference [(95% CI)^{(a)}] | P-value^{(b)} | | --- | --- | --- | --- | --- | | Primary Effectiveness Endpoints | | | | | | Time to Hemostasis (min) | | | | | | Mean ± STD (N) | 4.95±5.63(37) | 47.14±61.86(14) | -42.20[-62.52,-21.88] | 0.0242 | | Median, Range (Min, Max) | 2.0 (2.0, 30.0) | 17.5 (10.0, 220.0) | | | | Time to Ambulation (hr) | | | | | | Mean ± STD (N) | 4.25±4.35(36) | 8.63±6.02(14) | -4.39[-7.46,-1.31] | 0.0061 | | Median, Range (Min, Max) | 2.2 (1.2, 22.3) | 6.1 (3.6, 21.8) | | | | Secondary Effectiveness Endpoints | | | | | | Time to Eligibility for Hospital Discharge (hr) | | | | | | Mean ± STD (N) | 22.79±12.93(35) | 24.81±14.81(14) | -2.02[-10.59,6.55] | 0.6377 | | Median, Range (Min, Max) | 22.2 (2.1, 72.5) | 20.5 (0.0, 47.0) | | | | Time to Actual Hospital Discharge (hr) | | | | | | Mean ± STD (N) | 28.31±15.58(36) | 28.47±12.12(14) | -0.16[-9.48,9.16] | 0.9730 | | Median, Range (Min, Max) | 24.1 (17.3, 96.4) | 23.5 (14.9, 47.5) | | | | Time for Device Deployment (min) | | | | | | Mean ± STD (N) | 0.81±0.61(37) | - | - | - | | Median, Range (Min, Max) | 0.7 (0.1, 2.9) | | | | | Procedure Success | 31/37 (83.78%) | 8/14 (57.14%) | 26.64% [0.49, 52.64] | 0.0664 | | Device Success | 28/37 (75.68%) | 0/14 (0.00%) | 75.68% [48.97, 86.64] | <0.0001 | Numbers are Mean ± STD (Sample Size). Numbers of patients for the summary of continuous measures are based on number of non-missing values. (a) Two-sided 95% Confidence Intervals (CI) were calculated using Newcombe-Wilson Hybrid Score method for binary outcomes. Two sided 95% confidence intervals for continuous outcomes are based on least-squares estimation from analysis of variance. (b) P-values were calculated using unpaired t-test of inequality in mean differences of the continuous outcomes between 6F VCD and 6F MC group. Fisher Exact tests are used for comparison of binary outcomes between 6F VCD and 6F MC group. ## Sex/Gender-Specific Subgroup Analysis To evaluate for possible sex-based differences in outcome of treatment with the EXOSEAL VCD, sex/gender-specific analyses were performed on safety and effectiveness endpoints. The results suggest that the general conclusions of the overall study regarding both safety and effectiveness can be generalized for males and females. In the EXOSEAL 6F ECLIPSE trial ITT population, of the 267 subjects randomized to EXOSEAL VCD, 182 subjects were male (68.2%) and 85 subjects were female (31.8%). The proportions in the manual compression control group were similar (61.9% male, 38.1% female). In the EXOSEAL pooled 7F ITT population, of the 88 subjects randomized to EXOSEAL VCD, 63 subjects were male (71.6%) and 25 subjects were female (28.4%). In comparison, recently published rates of diagnostic and interventional catheterization procedures in the U.S. range from 59.7% to 68.8% for men and 31.2% to 40.3% for women [1, 2]. Tavris et al. have also shown that the percentage of women receiving therapy from a VCD decreases as the size of the catheter introducer sheath increases [3]. PMA P100013: FDA Summary of Safety and Effectiveness Data {20} The EXOSEAL 6F ECLIPSE trial and Mexican and German 7F trials were not powered to study safety or effectiveness of the EXOSEAL VCD versus Manual compression in sex-specific subgroups. The EXOSEAL 6F ECLIPSE trial and Mexican and German 7F trials primary and secondary endpoint data were assessed for differences between male and female subgroups, as well as for any interaction between treatment group and gender (Table 17). The results of these post hoc analyses are presented below in Tables 11-14. Table 11. Principal Effectiveness and Safety Results – Diagnostic Male Patients (ITT) Treated | Primary Effective Endpoints | 6F ECLIPSE Trial | | | | Pooled 7F VCD Data Compared to 6F MC Data | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | VCD (n=83 patients) | MC (n=35 patients) | P-Values(a) | Pooled 7F VCD (n=28 patients) | P-values(b) | | | | | Time to Hemostasis (min) | | | | | | | | | | Mean ± STD (N) | 3.48±5.09(83) | 15.12±6.24(34) | <0.0001 | 2.79 ±2.47 (28) | <0.0001 | | | | | Median, Range (Min, Max) | 2.00(2.00,34.00) | 15.00(3.00,25.00) | | 2.00(2.00,15.00) | | | | | | Time to Ambulation (hr) | | | | | | | | | | Mean ± STD (N) | 1.59±1.26(82) | 8.18±25.09(35) | 0.1299 | 1.94 ±4.36 (28) | 0.1576 | | | | | Median, Range (Min, Max) | 1.12(0.94,8.35) | 3.97(1.33,152.24) | | 1.08(0.98,24.18) | | | | | | Description of Event (Event Based) | 6F ECLIPSE Trial | | | | Pooled 7F VCD Data Compared to 6F MC Data | | | | | | VCD (n=83 patients) | MC (n=35 patients) | Difference VCD-MC^{1} Bound^{2} | P-Values^{3} | Pooled 7F VCD (n=28 patients) | Difference VCD-MC^{1} Bound^{2} | P-values^{4} | | | Major Adverse Events (Combined Event Rate) at 30-days | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | 0.0404 | 0/28(0.00%) | 0.00% | 10.15% | | Vascular Repair | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | 0.0404 | 0/28(0.00%) | 0.00% | 10.15% | | Access site-related bleeding requiring transfusion | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | 0.0404 | 0/28(0.00%) | 0.00% | 10.15% | | Access site-related infection requiring treatment | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | 0.0404 | 0/28(0.00%) | 0.00% | 10.15% | | Any new documented ipsilateral lower extremity ischemia | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | 0.0404 | 0/28(0.00%) | 0.00% | 10.15% | | Surgery for access site-related nerve injury | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | 0.0404 | 0/28(0.00%) | 0.00% | 10.15% | | Permanent(>30 days) access site-related nerve injury | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | 0.0404 | 0/28(0.00%) | 0.00% | 10.15% | | Secondary Adverse Events (Combined Event Rate) at 30-days | 3/83(3.61%) | 0/35(0.00%) | 3.61% | 9.08% | - | 1/28(3.57%) | 3.57% | 15.85% | | Rebleeding Following Initial Hemostasis | 1/83(1.20%) | 0/35(0.00%) | 1.20% | 5.59% | - | 0/28(0.00%) | 0.00% | 10.15% | | Pseudoaneurysm not Requiring Treatment | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Treated Pseudoaneurysm | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Documented Arteriovenous Fistula | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Access Site Hematoma >= 6cm | 1/83(1.20%) | 0/35(0.00%) | 1.20% | 5.59% | - | 1/28(3.57%) | 3.57% | 15.85% | | Access Site-Related Bleeding Requiring > 30 min for Hemostasis | 1/83(1.20%) | 0/35(0.00%) | 1.20% | 5.59% | - | 0/28(0.00%) | 0.00% | 10.15% | | Post-Hospital Discharge Access Site-Related Bleeding | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Ipsilateral Lower Extremity Arterial Emboli | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Transient Loss of Ipsilateral Lower Extremity Pulse | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Ipsilateral Deep Vein Thrombosis | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Access Site-Related Vessel Laceration | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Transient Access Site-Related Nerve Injury | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Access Site Wound Dehiscence | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Treated, Localized Access Site Infection | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Retroperitoneal Bleeding | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Ipsilateral Peripheral Artery Total Occlusion | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Ecchymosis >= 6cm | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Intraluminal Plug Delivery Not Requiring Surgical Intervention | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Decrease in Pedal Pulse | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | | Death | 0/83(0.00%) | 0/35(0.00%) | 0.00% | 3.68% | - | 0/28(0.00%) | 0.00% | 10.15% | Numbers are % (counts/sample size) or Mean ± STD (Sample Size). Numbers of patients for the summary of continuous measures are based on number of non-missing values. (a) P-values were calculated using unpaired t-test of inequality in mean differences of the continuous outcomes between 6F VCD and 6F MC group PMA P100013: FDA Summary of Safety and Effectiveness Data {21} (6) P-values were calculated using unpaired t-test of inequality in mean differences of the continuous outcomes between pooled 7F VCD and 6F MC group (7) Proportion differences between 6F VCD group and 6F MC group (P_{VCD} - P_{MC}) One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between 6F VCD group and 6F MC group (P_{VCD} - P_{MC}). The calculation was performed using unconditional exact method P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (6F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. (8) Proportion differences between pooled 7F VCD group and 6F MC group (P_{VCD} - P_{MC}) One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between pooled 7F VCD group and 6F MC group (P_{VCD} - P_{MC}). The calculation was performed using unconditional exact method P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (7F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. Table 12. Principal Effectiveness and Safety Results – Diagnostic Female Patients (ITT) Treated | Primary Effective Endpoints | 6F ECLIPSE Trial | | | | | Pooled 7F VCD Data Compared to 6F MC Data | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | VCD (n=51 patients) | MC (n=31 patients) | | P-Values(a) | | Pooled 7F VCD (n=15 patients) | | P-values(b) | | | Time to Hemostasis (min) | | | | | | | | | | | Mean ± STD (N) | 3.10±4.50(51) | 14.45±5.48(31) | | <0.0001 | | 3.00 ±3.34 (15) | | <0.0001 | | | Median, Range (Min, Max) | 2.00(2.00,25.00) | 15.00(5.00,30.00) | | | | 2.00(2.00,15.00) | | | | | Time to Ambulation (hr) | | | | | | | | | | | Mean ± STD (N) | 1.58±1.19(51) | 4.88±3.72(31) | | <0.0001 | | 2.52 ±5.93 (15) | | 0.1733 | | | Median, Range (Min, Max) | 1.10(0.99,6.94) | 4.16(2.28,24.29) | | | | 1.05(0.01,23.94) | | | | | Description of Event (Event Based) | 6F ECLIPSE Trial | | | | | Pooled 7F VCD Data Compared to 6F MC Data | | | | | | VCD (n=51 patients) | MC (n=31 patients) | Difference VCD-MC¹ | Upper Bound² | P-Values³ | Pooled 7F VCD (n=15 patients) | Difference VCD-MC¹ | Upper Bound² | P-values⁴ | | Major Adverse Events (Combined Event Rate) at 30-days | 0/51 (0.00%) | 0/31 (0.00%) | 0.00% | 5.70% | 0.1247 | 0/15 (0.00%) | 0.00% | 18.10% | 0.5421 | | Vascular Repair | 0/51 (0.00%) | 0/31 (0.00%) | 0.00% | 5.70% | 0.1247 | 0/15 (0.00%) | 0.00% | 18.10% | 0.5421 | | Access site-related bleeding requiring transfusion | 0/51 (0.00%) | 0/31 (0.00%) | 0.00% | 5.70% | 0.1247 | 0/15 (0.00%) | 0.00% | 18.10% | 0.5421 | | Access site-related infection requiring treatment | 0/51 (0.00%) | 0/31 (0.00%) | 0.00% | 5.70% | 0.1247 | 0/15 (0.00%) | 0.00% | 18.10% | 0.5421 | | Any new documented ipsilateral lower extremity ischemia | 0/51 (0.00%) | 0/31 (0.00%) | 0.00% | 5.70% | 0.1247 | 0/15 (0.00%) | 0.00% | 18.10% | 0.5421 | | Surgery for access site-related nerve injury | 0/51 (0.00%) | 0/31 (0.00%) | 0.00% | 5.70% | 0.1247 | 0/15 (0.00%) | 0.00% | 18.10% | 0.5421 | | Permanent(>30 days) access site-related nerve injury | 0/51 (0.00%) | 0/31 (0.00%) | 0.00% | 5.70% | 0.1247 | 0/15 (0.00%) | 0.00% | 18.10% | 0.5421 | | Secondary Adverse Events (Combined Event Rate) at 30-days | 1/51(1.96%) | 1/31(3.23%) | -1.27% | 6.03% | - | 0/15 (0.00%) | -3.23% | 12.64% | - | | Rebleeding Following Initial Hemostasis | 1/51(1.96%) | 1/31(3.23%) | -1.27% | 6.03% | - | 0/15 (0.00%) | -3.23% | 12.64% | - | | Pseudoaneurysm not Requiring Treatment | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Treated Pseudoaneurysm | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Documented Arteriovenous Fistula | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Access Site Hematoma >= 6cm | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Access Site-Related Bleeding Requiring > 30 min for Hemostasis | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Post-Hospital Discharge Access Site-Related Bleeding | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Ipsilateral Lower Extremity Arterial Emboli | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Transient Loss of Ipsilateral Lower Extremity Pulse | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Ipsilateral Deep Vein Thrombosis | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Access Site-Related Vessel Laceration | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Transient Access Site-Related Nerve Injury | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Access Site Wound Dehiscence | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Treated, Localized Access Site Infection | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Retroperitoneal Bleeding | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Ipsilateral Peripheral Artery Total Occlusion | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Echymosis >= 6cm | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Intraluminal Plug Delivery Not Requiring Surgical Intervention | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Decrease in Pedal Pulse | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | | Death | 0/51(0.00%) | 0/31(0.00%) | 0.00% | 5.70% | - | 0/15 (0.00%) | 0.00% | 18.10% | - | Numbers are % (counts/sample size) or Mean ± STD (Sample Size). Numbers of patients for the summary of continuous measures are based on number of non-missing values. (a) P-values were calculated using unpaired t-test of inequality in mean differences of the continuous outcomes between 6F VCD and 6F MC group (b) P-values were calculated using unpaired t-test of inequality in mean differences of the continuous outcomes between pooled 7F VCD and 6F MC group PMA P100013: FDA Summary of Safety and Effectiveness Data {22} 1. Proportion differences between 6F VCD group and 6F MC group (P$_{VCD}$ - P$_{MC}$) 2. One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between 6F VCD group and 6F MC group (P$_{VCD}$ - P$_{MC}$). The calculation was performed using unconditional exact method 3. P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (6F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. 4. Proportion differences between pooled 7F VCD group and 6F MC group (P$_{VCD}$ - P$_{MC}$) 5. One-sided upper bound of 95% Confidence Intervals (CI) of the difference of two binomial proportions: between pooled 7F VCD group and 6F MC group (P$_{VCD}$ - P$_{MC}$). The calculation was performed using unconditional exact method 6. P-values were calculated using unconditional exact test of non-inferiority using difference of two binomial proportions (7F VCD group vs. 6F MC group) with the pre-specified margin of 4.0%. The calculation was performed using StatXact. Table 13. Principal Effectiveness and Safety Results – Interventional Male Patients (ITT) Treated | Primary Effective Endpoints | 6F ECLIPSE Trial | | | | Pooled 7F VCD Data Compared to 6F MC Data | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | VCD (n=99 patients) | MC (n=48 patients) | P-Values(a) | Pooled 7F VCD (n=35 patients) | P-values(b) | | | | | Time to Hemostasis (min) | | | | | | | | | | Mean ± STD (N) | 5.55±17.73(99) | 28.17±35.64(47) | 0.0001 | 3.89 ±5.90 (35) | <0.0001 | | | | | Median, Range (Min, Max) | 2.00(2.00,175.00) | 20.00(10.00,220.00) | | 2.00(2.00,35.00) | | | | | | Time to Ambulation (hr) | | | | | | | | | | Mean ± STD (N) | 3.13±3.90(97) | 6.04±3.84(46) | <0.0001 | 3.66 ±6.60 (35) | 0.0633 | | | | | Median, Range (Min, Max) | 1.95(0.88,22.30) | 4.98(3.00,21.83) | | 1.08(0.98,24.32) | | | | | | Description of Event (Event Based) | 6F ECLIPSE Trial | | | | Pooled 7F VCD Data Compared to 6F MC Data | | | | | | VCD (n=99 patients) | MC (n=48 patients) | Difference VCD-MC¹ | Upper Bound² | P-Values³ | Pooled 7F VCD (n=35 patients) | Difference VCD-MC¹ | Upper Bound² | | Major Adverse Events (Combined Event Rate) at 30-days | 0/99 (0.00%) | 0/48 (0.00%) | 0.00% | 3.29% | 0.0307 | 0/35 (0.00%) | 0.00% | 8.20% | | Vascular Repair | 0/99 (0.00%) | 0/48 (0.00%) | 0.00% | 3.29% | 0.0307 | 0/35 (0.00%) | 0.00% | 8.20% | | Access site-related bleeding requiring transfusion | 0/99 (0.00%) | 0/48 (0.00%) | 0.00% | 3.29% | 0.0307 | 0/35 (0.00%) | 0.00% | 8.20% | | Access site-related infection requiring treatment | 0/99 (0.00%) | 0/48 (0.00%) | 0.00% | 3.29% | 0.0307 | 0/35 (0.00%) | 0.00% | 8.20% | | Injury new documented ipsilateral lower extremity ischemia | 0/99 (0.00%) | 0/48 (0.00%) | 0.00% | 3.29% | 0.0307 | 0/35 (0.00%) | 0.00% | 8.20% | | Surgery for access site-related nerve injury | 0/99 (0.00%) | 0/48 (0.00%) | 0.00% | 3.29% | 0.0307 | 0/35 (0.00%) | 0.00% | 8.20% | | Permanent(>30 days) access site-related nerve injury | 0/99 (0.00%) | 0/48 (0.00%) | 0.00% | 3.29% | 0.0307 | 0/35 (0.00%) | 0.00% | 8.20% | | Secondary Adverse Events (Combined Event Rate) at 30-days | 17/99(17.17%) | 3/48(6.25%) | 10.92% | 19.53% | - | 1/35(2.86%) | -3.39% | 6.24% | | Rebleeding Following Initial Hemostasis | 9/99(9.09%) | 0/48(0.00%) | 9.09% | 15.33% | - | 0/35(0.00%) | 0.00% | 8.20% | | Pseudoaneurysm not Requiring Treatment | 0/99(0.00%) | 0/48(0.00%) | 0.00% | 3.29% | - | 0/35(0.00%) | 0.00% | 8.20% | | Treated Pseudoaneurysm | 0/99(0.00%) | 0/48(0.00%) | 0.00% | 3.29% | - | 0/35(0.00%) | 0.00% | 8.20% | | Documented Arteriovenous Fistula | 0/99(0.00%) | 0/48(0.00%) | 0.00% | 3.29% | - | 0/35(0.00%) | 0.00% | 8.20% | | Access Site Hematoma >= 6cm | 5/99(5.05%) | 1/48(2.08%) | 2.97% | 8.54% | - | 1/35(2.86%) | 0.77% | 10.02% | | Access Site-Related Bleeding Requiring > 30 min for Hemostasis | 0/99(0.00%) | 1/48(2.08%) | -2.08% | 1.11% | - | 0/35(0.00%) | -2.08% | 5.51% | | Post-Hospital Discharge Access Site-Related Bleeding | 0/99(0.00%) | 0/48(0.00%) | 0.00% | 3.29% | - | 0/35(0.00%) | 0.00% | 8.20% | | Ipsilateral Lower Extremity Arterial Emboli | 0/99(0.00%) | 0/48(0.00%) | 0.00% | 3.29% | - | 0…