I.  **General Information**

> Device Generic Name: Vascular hemostasis device
>
> Device Trade Name: QuickSeal™ Femoral Arterial Closure System
>
> Applicant's Name and Address SUB-Q, Inc.
>
> 1062-D Calle Negocio
>
> San Clemente, CA 92673
>
> Premarket Approval Application Number: P010049
>
> Date of Panel recommendation: None
>
> Date of Notice of Approval to Applicant: March 25, 2002

# **Indications for Use**

> The QuickSeal Femoral Arterial Closure System is intended for the
> delivery of Gelfoam for "extravascular" closure of femoral artery
> access sites. The system is indicated for use in reducing time to
> hemostasis, at femoral artery puncture sites and in reducing time to
> ambulation in patients who have undergone diagnostic or interventional
> procedures using 8 French or smaller procedural sheaths. The device
> reduces time to eligibility for hospital discharge in patients who
> have undergone diagnostic or interventional procedures and reduces
> time to actual hospital discharge in patients who have undergone
> diagnostic procedures

# **Contraindications**

> This product is not intended for intravascular use.
>
> The QuickSeal should not be used in patients who have a sensitivity or
> allergy to porcine derived material.
>
> The QuickSeal should not be used if posterior arterial wall puncture
> is suspected, as this may lead to bleeding complications.

# **Warnings and Precautions**

> The warnings and precautions can be found in the QuickSeal Femoral
> Arterial Closure System labeling

# **Device Description**

A.  **Materials and Configuration**

This device system delivers a hydrated absorbable hemostatic foam
material (Gelfoam) extravascularly to a femoral artery access site. The
device system comes to the user as a kit packaged in a box. Inside the
box are several items that are sterile inside their own individual
packages.

The components of the system (Device Version 1.9) are:

-   [Gelfoam]{.underline} resorbable hemostatic sponge

-   Single-use disposable 3cc [syringe]{.underline} used to advance the
    Gelfoam to the distal end of the Introduction Catheter.

-   Single-use disposable .025" J-tipped [guidewire]{.underline} used as
    a transfer tool to guide the Depth Marker, Pusher and the
    Introduction Catheter containing the Gelfoam to the target site.

-   Single-use disposable [Depth Marker w/Depth Indicator]{.underline}
    ring used to identify and set the depth of the tract on the
    Introduction Catheter.

-   Single-use disposable [Introduction Catheter w/Depth Indicator
    ring]{.underline}

-   [Cutting Tab]{.underline} for uniform Gelfoam sizing

-   Single-use disposable [Pusher]{.underline} used to deploy and ensure
    the Gelfoam is left in place adjacent to the external vessel wall.

-   Single-use disposable [Hydration Chamber]{.underline} used to
    hydrate the Gelfoam with sterile saline. The [Chamber
    Connector]{.underline} is used to connect the Hydration Chamber to
    the Introduction catheter.

    A.  **Principals of Operation**

> The use of the device requires two trained persons. Manual compression
> is applied in conjunction with the use of the device.
>
> The Cutting Tab is provided to cut the Gelfoam to size. The Gelfoam
> sponge is placed in the Hydration Chamber and is hydrated with sterile
> saline using the 3cc syringe. The hydrated Gelfoam is then staged in
> the Introduction Catheter to facilitate the delivery process.
>
> The Gelfoam is delivered extravascularly into the arterial access site
> directly over a Guidewire by using a "pin and pull" technique. The
> placement of the Gelfoam is just proximal to the outer vessel wall of
> the
>
> arterial access site and is left in place to promote hemostasis at the
> arterial puncture site.

# **Alternative Practices and Procedures**

> Alternative practices for achieving hemostasis of the femoral artery
> puncture site post-catheterization include manual compression,
> mechanical compression, collagen hemostasis devices, and percutaneous
> delivery of sutures to the femoral artery access site. Pressure
> dressings and sandbags are routinely used in combination with
> compression methods to control oozing.

# **Marketing History**

> The QuickSeal Femoral Arterial Closure System has not been marketed
> in the United States or any foreign country.

# **Adverse Effects of the Device on Health**

## 

> The QuickSeal Femoral Arterial Closure System was evaluated in a
> randomized controlled clinical investigation involving 398 patients
> within the U.S. The QuickSeal Device was compared to Manual
> Compression methods following interventional and diagnostic
> catheterization procedures with 8 Fr and smaller sheath sizes. Prior
> to enrollment of randomized patients, each site enrolled
> non-randomized QuickSeal run-in patients for training purposes. There
> were a total of eighty-one (81) patients enrolled as non-randomized
> QuickSeal run-in patients. Of the 398 randomized patients, 240 (60%)
> were randomized to QuickSeal and 158 (40%) were randomized to Manual
> Compression. Of the patients randomized to QuickSeal, 145 (60%) were
> interventional and 95 (40 %) were diagnostic. Of the patients
> randomized to manual compression, 100 (63%) were interventional and 58
> (37%) were diagnostic.
>
> One death was reported during the randomized investigation, which was
> determined not to be device-related. This patient was randomized to
> the QuickSeal device.
>
> Closure method related adverse events seen in the clinical study were:

-   Hematoma

-   Bleeding requiring transfusion

-   Pseudoaneurysm not requiring treatment

-   Pseudoaneurysm requiring thrombin injection

-   Retroperitoneal bleed

> Potential complications of allergic reaction, adhesion formation,
> infection or abscess, foreign body reaction, wound dehiscence or
> vessel occlusion [were not seen.]{.underline}
>
> Table 1 summarizes the adverse events reported within the randomized
> investigation's 30-day follow-up period. Events are summarized by
> percentage of randomized patients experiencing the event during the
> clinical investigation.

Table 1: Incidence of all adverse events in randomized patients

Number (Percentage) of Patients with an Event

+--------------------------------+------------+-----------+-----------+
| **Description of Event**       | **Q        | **Manual  | D         |
|                                | uickSeal** | Comp      | ifference |
|                                |            | ression** |           |
|                                | N= 240     |           | \[95%     |
|                                |            | N= 158    | C.I.\]    |
|                                |            |           | (a)       |
+--------------------------------+------------+-----------+-----------+
| **Closure method related**     | 2 (0.8%)   | 0 (0.0%)  | (-100,    |
|                                | (d)        |           | 1.8)      |
| Vascular damage requiring      |            | 0 (0.0%)  |           |
| repair                         | 1 (0.4%)   |           | (-100,    |
|                                | (e)        | 1 (0.6%)  | 1.8)      |
| Retroperitoneal bleed          |            | (f)       |           |
|                                | 0 (0.0%)   |           | (-100,    |
| Hematoma                       |            | **1       | 1.8)      |
|                                | **3        | (0.6%)**  |           |
| **Total**                      | (1.3%)**   |           | (-100,    |
|                                |            |           | 2.2)      |
+--------------------------------+------------+-----------+-----------+
| **Non-closure method related** | 23 (9.6%)  | 12 (7.6%) |           |
|                                |            |           |           |
| Mild**\***                     | 4 (1.7%)   | 2 (1.3%)  |           |
|                                |            |           |           |
| Moderate**\***                 | 6 (2.5%)   | 4 (2.5%)  |           |
|                                |            |           |           |
| Severe**\***                   | **33       | **18      |           |
|                                | (13.8%)**  | (11.4%)** |           |
| **Total**                      |            |           |           |
+--------------------------------+------------+-----------+-----------+
| **Minor adverse events**       | 33 (13.8%) | 13 (8.2%) | (-100,    |
|                                |            |           | 10.7)     |
| Hematoma (2cm -- 6cm)          | 4 (1.7%)   | 0 (0.0%)  |           |
|                                |            |           | (-100,    |
| Hematoma \> 6cm                | 17 (7.1%)  | 12 (7.6%) | 3.0)      |
|                                |            |           |           |
| Ecchymosis                     | 5 (2.1%)   | 3 (1.9%)  | ( -100,   |
|                                |            |           | 3.9)      |
| Bleeding                       | 1 (0.4%)   | 0 (0.0%)  |           |
|                                |            |           | (-100,    |
| Minor pseudoaneurysm requiring | **50       | **24      | 2.5)      |
| no intervention                | (20.8%)**  | (15.2%)** |           |
|                                |            |           | ( -100,   |
| **Total Minor Complications**: |            |           | 1.1)      |
|                                |            |           |           |
|                                |            |           | (-100,    |
|                                |            |           | 12.0)     |
+--------------------------------+------------+-----------+-----------+
| Device Failure (b)             | 8 (3.3%)   | N/A       |           |
+--------------------------------+------------+-----------+-----------+
| Procedure Failure (c)          | 5 (2.1%)   | 1 (0.6%)  |           |
+--------------------------------+------------+-----------+-----------+

\(a\) 95% C.I. represents a one sided confidence interval of the true
difference between the percentage of patients with complications
(QuickSeal- Control)

\(b\) Device failure rate was defined as the number of patients in which
hemostasis was not achieved using the QuickSeal device or a major
complication occurred.

\(c\) Procedure failure rate was defined as the number of patients in
which hemostasis was not achieved, or a major complication occurred.

\(d\) Both patients experienced a pseudoaneurysm requiring a thrombin
injection.

\(e\) Patient experienced a hematoma requiring a transfusion (one unit
of packed red blood cells).

\(f\) Patient experienced a 10 x 10 cm hematoma requiring a transfusion
(two units of packed red blood cells).

**\***As determined by the investigational site

# **Summary of non-clinical Studies**

###### **Bench and In Vitro Device Characterization Testing**

## **Biocompatibility**

> Biocompatibility testing of the QuickSeal Delivery System was
> conducted in accordance with the FDA-modified matrix of ISO 10993-1,
> "Biological Evaluation of Medical Devices, Part 1: Evaluation and
> Testing". The following tests were conducted: cytotoxicity, systemic
> toxicity, hemolysis, sensitization, irritation, and pyrogenicity. The
> results indicated that the QuickSeal Delivery System is non-toxic,
> non-hemolytic, non-irritant and non-pyrogenic.
>
> The Gelfoam, syringe and guidewire were previously approved for
> commercial distribution.

## **Functionality**

> In vitro tests were conducted to characterize the mechanical
> performance of the QuickSeal Femoral Arterial Closure System. Results
> from the mechanical tests demonstrated that the QuickSeal Femoral
> Arterial Closure System performance was acceptable. The tests are
> summarized in Table 2.

Table 2.

QuickSeal FUNCTIONAL TEST TABLE

+---------------+----------+------+----------------------------+------+
| Bench Test    | Purpose  | Nu   | Acceptance Criteria        | Res  |
|               |          | mber |                            | ults |
|               |          | of   |                            |      |
|               |          | Test |                            |      |
|               |          | U    |                            |      |
|               |          | nits |                            |      |
+---------------+----------+------+----------------------------+------+
| 12 Fr         | To       | 15   | a)Visual discrepancies     | Pass |
| Introduction  | verify   |      |                            |      |
| Catheter --   | the      |      | b\) .122 pin gauge must    |      |
| original      | safety   |      | pass through lumen of      |      |
| design        | and      |      | Introduction Catheter with |      |
|               | efficacy |      | ease (no binding).         |      |
|               | of the   |      |                            |      |
|               | design   |      | c\) Vent Cap must remain   |      |
|               | of the   |      | attached to the tube of    |      |
|               | Intr     |      | the Introduction Catheter  |      |
|               | oduction |      | when a pull force of 2.5   |      |
|               | Catheter |      | pounds is exerted          |      |
|               |          |      |                            |      |
|               |          |      | d\) Female Luer connector  |      |
|               |          |      | must stay attached to the  |      |
|               |          |      | tube of the Introduction   |      |
|               |          |      | Catheter when a 10 pound   |      |
|               |          |      | force is applied for 15    |      |
|               |          |      | seconds                    |      |
+---------------+----------+------+----------------------------+------+
| 9 Fr Pusher-  | To       | 15   | a\) Visually inspect parts | Pass |
| original      | verify   |      | for discrepancies          |      |
| design        | the      |      |                            |      |
|               | safety   |      | b\) A .035 Guidewire must  |      |
|               | and      |      | pass through the lumen of  |      |
|               | efficacy |      | the Pusher easily without  |      |
|               | of the   |      | binding.                   |      |
|               | Pusher   |      |                            |      |
|               |          |      | c\) The Female luer        |      |
|               |          |      | connector must stay        |      |
|               |          |      | attached to the Pusher     |      |
|               |          |      | shaft when a 5 pound force |      |
|               |          |      | is applied for 15 seconds  |      |
+---------------+----------+------+----------------------------+------+
| System Design | To       | 15   | a\) Visually inspect parts | Pass |
| Verification- | verify   |      | for discrepancies          |      |
| original      | the      |      |                            |      |
| design        | safety   |      | b\) No leaks are present   |      |
|               | and      |      | at the male/female luer    |      |
|               | efficacy |      | connections when a 50 psi  |      |
|               | of the   |      | is applied using a 3cc     |      |
|               | Ir       |      | syringe filled with        |      |
|               | rigation |      | distilled water for 10     |      |
|               | Syringe  |      | seconds.                   |      |
|               | System   |      |                            |      |
|               | (H       |      |                            |      |
|               | ydration |      |                            |      |
|               | Chamber  |      |                            |      |
|               | and      |      |                            |      |
|               | con      |      |                            |      |
|               | nectors) |      |                            |      |
+---------------+----------+------+----------------------------+------+
| Depth Marker- | To       | 15   | a\) Visually inspect parts | Pass |
| original      | verify   |      | for discrepancies          |      |
| design        | the      |      |                            |      |
|               | safety   |      | b\) A .035 diameter        |      |
|               | and      |      | Guidewire must pass        |      |
|               | efficacy |      | through the lumen of the   |      |
|               | of the   |      | Depth Gauge easily without |      |
|               | Depth    |      | binding.                   |      |
|               | Marker   |      |                            |      |
+---------------+----------+------+----------------------------+------+
| Foam Cutter   | To       | 30   | a\) Gelfoam (3 samples)    | Pass |
|               | verify   |      | cut using the new Foam     |      |
|               | the      |      | Cutter must be the same    |      |
|               | safety   |      | size and exhibit similar   |      |
|               | and      |      | edges as the Gelfoam cut   |      |
|               | efficacy |      | with the previous cutting  |      |
|               | of the   |      | device/template.           |      |
|               | new      |      |                            |      |
|               | cutter   |      | b\) The Foam Cutter is to  |      |
|               | device   |      | remain attached to the     |      |
|               | for use  |      | Presentation Card when a   |      |
|               | with the |      | 6-pound pull force is      |      |
|               | Q        |      | applied.                   |      |
|               | uickSeal |      |                            |      |
|               | Femoral  |      |                            |      |
|               | Arterial |      |                            |      |
|               | Closure  |      |                            |      |
|               | System   |      |                            |      |
+---------------+----------+------+----------------------------+------+
| Depth Marker  | To       | 30   | a\) Bend the tube (body)   | Pass |
| -- design     | verify   |      | of the Depth Marker        |      |
| change        | the      |      | approximately 30 degrees.  |      |
|               | safety   |      | Verify the tube flexes     |      |
| Note:         | and      |      | without kinking or         |      |
|               | efficacy |      | fracturing.                |      |
| Because of    | of the   |      |                            |      |
| the addition  | modified |      | b\) A .035 Guidewire shall |      |
| of the insert | Depth    |      | pass through the lumen of  |      |
| molded        | Marker   |      | the Depth Marker easily,   |      |
| handle, a     | with an  |      | without friction.          |      |
| pull force    | insert   |      |                            |      |
| and bend test | molded   |      | c\) Verify the handle of   |      |
| was           | handle   |      | the Depth Marker can       |      |
| incorporated  |          |      | withstand a 5-pound pull   |      |
| into the      |          |      | force without separating   |      |
| design        |          |      | from the tube.             |      |
| verification  |          |      |                            |      |
| to assure     |          |      |                            |      |
| that the      |          |      |                            |      |
| molding       |          |      |                            |      |
| process does  |          |      |                            |      |
| not weaken    |          |      |                            |      |
| the shaft and |          |      |                            |      |
| that the      |          |      |                            |      |
| handle is     |          |      |                            |      |
| securely      |          |      |                            |      |
| attached to   |          |      |                            |      |
| the shaft.    |          |      |                            |      |
+---------------+----------+------+----------------------------+------+
| Introduction  | To       | 30   | a\) Following the          | Pass |
| Catheter --   | verify   |      | Instructions for Use,      |      |
| design change | the      |      | prepare, hydrate and stage |      |
|               | safety   |      | the Gelfoam pledget.       |      |
| Note:         | and      |      | Verify the Introduction    |      |
|               | efficacy |      | Catheter functions as      |      |
| Because of    | of the   |      | described in the IFU and   |      |
| the addition  | modified |      | that there are no leaks or |      |
| of an insert  | Intr     |      | separations of the         |      |
| molded        | oduction |      | components/connectors.     |      |
| handle, a     | Catheter |      |                            |      |
| pull force    | with an  |      | b\) Expose the             |      |
| was           | insert   |      | Introduction Catheter/Vent |      |
| incorporated  | molded   |      | Cap connection to 200-psi  |      |
| into the      | handle   |      | pressure and hold for 5    |      |
| design        | and tip  |      | seconds, staging the       |      |
| verification  | formed   |      | Gelfoam pledget. Verify    |      |
| to assure     | end      |      | the vent cap remains       |      |
| that the      |          |      | attached to the            |      |
| handle is     |          |      | Introduction Catheter      |      |
| securely      |          |      | during staging.            |      |
| attached to   |          |      |                            |      |
| the shaft.    |          |      | c\) Verify there are no    |      |
| The change to |          |      | leaks at the luer cap      |      |
| thermal       |          |      | attachment point of the    |      |
| forming of    |          |      | Introduction Catheter when |      |
| the distal    |          |      | exposed to 50 psi.         |      |
| end of the    |          |      |                            |      |
| cannula       |          |      | d\) Verify the handle can  |      |
| requires a    |          |      | withstand a minimum of 3   |      |
| test to       |          |      | pounds of pull force       |      |
| assure that   |          |      | without separating from    |      |
| no leaks are  |          |      | the shaft.                 |      |
| present       |          |      |                            |      |
| during foam   |          |      |                            |      |
| staging and   |          |      |                            |      |
| also requires |          |      |                            |      |
| a pressure    |          |      |                            |      |
| test to ensue |          |      |                            |      |
| that the      |          |      |                            |      |
| interface fit |          |      |                            |      |
| between       |          |      |                            |      |
| cap/cannula   |          |      |                            |      |
| can withstand |          |      |                            |      |
| normal use of |          |      |                            |      |
| the system    |          |      |                            |      |
| during        |          |      |                            |      |
| staging.      |          |      |                            |      |
+---------------+----------+------+----------------------------+------+
| System        | To       | 30   | a\) Visually inspect the   | Pass |
| Irrigation    | verify   |      | units for defects, such as |      |
| Design        | the      |      | cracking. Cracking would   |      |
| Verification  | safety   |      | indicate a failure.        |      |
| -- design     | and      |      |                            |      |
| change        | efficacy |      | b\) Pressurize the         |      |
|               | of the   |      | hydration chamber with the |      |
| Note:         | chamber  |      | chamber luer attached to   |      |
|               | luer     |      | 200 psi. and hold for 5    |      |
| The change to | when     |      | seconds. Verify the        |      |
| a removable   | used     |      | chamber does not leak and  |      |
| chamber luer  | with the |      | the luer remains attached  |      |
| that          | h        |      | to the chamber body.       |      |
| mechanically  | ydration |      |                            |      |
| attached to   | chamber. |      | c\) Prepare, hydrate and   |      |
| the proximal  |          |      | stage the Gelfoam,         |      |
| end of the    |          |      | following the Instructions |      |
| hydration     |          |      | for Use.                   |      |
| chamber       |          |      |                            |      |
| requires a    |          |      |                            |      |
| leak test and |          |      |                            |      |
| hydraulic     |          |      |                            |      |
| pressure test |          |      |                            |      |
| to ensure the |          |      |                            |      |
| o-ring seals  |          |      |                            |      |
| and the       |          |      |                            |      |
| mechanical    |          |      |                            |      |
| engagement    |          |      |                            |      |
| can withstand |          |      |                            |      |
| the hydration |          |      |                            |      |
| and staging   |          |      |                            |      |
| foam          |          |      |                            |      |
| operations    |          |      |                            |      |
| required by   |          |      |                            |      |
| the system.   |          |      |                            |      |
+---------------+----------+------+----------------------------+------+
| QuickSeal     | To       | 30   | a\) Introduction Catheter  | Pass |
| System Design | verify   |      | and Hydration Chamber      |      |
| Verification  | the      |      | remain attached during     |      |
| -- design     | safety   |      | staging                    |      |
| change --     | and      |      |                            |      |
| pre-assembled | efficacy |      | b\) Gelfoam hydrates as in |      |
| device        | of the   |      | previous design.           |      |
|               | Q        |      |                            |      |
| Note: The     | uickSeal |      |                            |      |
| change to a   | Femoral  |      |                            |      |
| pre-assembled | Arterial |      |                            |      |
| device with a | Closure  |      |                            |      |
| mechanical    | System   |      |                            |      |
| /interference | when     |      |                            |      |
| fit between   | pre-as   |      |                            |      |
| the distal    | sembled. |      |                            |      |
| end of the    |          |      |                            |      |
| cannula and   |          |      |                            |      |
| the hydration |          |      |                            |      |
| chamber luer  |          |      |                            |      |
| requires leak |          |      |                            |      |
| testing,      |          |      |                            |      |
| hydraulic     |          |      |                            |      |
| pressure      |          |      |                            |      |
| testing that  |          |      |                            |      |
| simulate      |          |      |                            |      |
| actual        |          |      |                            |      |
| hydration and |          |      |                            |      |
| staging of    |          |      |                            |      |
| the foam.     |          |      |                            |      |
+---------------+----------+------+----------------------------+------+

**Sterilization and Shelf Life**

The device is packaged as a kit in a Tyvek pouch. Several components are
purchased as sterile by the sponsor from outside sources; the Gelfoam
resorbable hemostatic sponge, single-use 3 cc disposable syringe and
single-use 0.025" disposable J-tipped guidewire. The QuickSeal Delivery
System is sterilized using EtO. The sponsor has provided a statement of
conformance with standards for EtO residuals.

> This device has been approved with a 6-month shelf life after review
> of the sponsor's 6-unit visual inspection protocol of
> shipping/handling.

A.  **Pre-Clinical Animal Studies**

##### **Preclinical animal studies**

> Animal studies were performed using the porcine model in both
> non-heparinized and heparinized animals. The studies were performed at
> two academic institutions with the assistance of SubQ personnel.
>
> The QuickSeal Femoral Arterial Closure system was used on a punctured
> femoral artery accessed using the standard Seldinger technique. Seven
> animals were studied and 13 femoral arteries were studied. The device
> could be used in all 13 arteries.
>
> The study was organized into two distinct chronic periods: 24-48 hours
> and 14-21 days. Six data points in three animals were acquired for the
> 24-48 hours period at one center and seven data points in 4 animals
> were acquired for the 14-21 days period at the other center.
>
> **Endpoints** evaluated:

-   **Time to hemostasis** (TTH) -- determined by direct observation

-   **Angiography**, using the carotid artery accessed by a cut down,
    was performed at 24 hours and 14-16 days post-procedure **to
    determine vessel patency.**

-   **Histopathology** was performed of the puncture site and of the
    perivascular and subcutaneous tissue.

> The average time to hemostasis in both chronic periods was 1 minute.
> No abnormal behavior or changes in the physical characteristics of any
> limb were recorded throughout the chronic period.
>
> Angiography examinations of post 24 hour and 14-16 day chronic periods
> showed complete vessel patency with no signs of intravascular delivery
> or vessel extravasation.
>
> Histopathology of the blood vessels did not show any documentation of
> vessel obstruction. There were several instances of mild endothelial
> loss documented.

#  {#section-1 .unnumbered}

# **Clinical Studies**

#  {#section-2 .unnumbered}

> The QuickSeal Femoral Arterial Closure System was evaluated in a
> randomized controlled multi-center clinical investigation involving
> 398 patients within the U.S. The QuickSeal Device was compared to
> Manual Compression methods following interventional and diagnostic
> catheterization procedures with 8 Fr and smaller sheath sizes. Prior
> to enrollment of randomized patients, eighty-one (81) patients were
> enrolled as non-randomized QuickSeal run-in patients.
>
> The study was conducted at 10 U.S. institutions from July of 2000 to
> June of 2001. Only 9 sites enrolled patients. A 3:2 device-to-control
> randomization was used with randomization stratified according to type
> of procedure (interventional or diagnostic). Of the 398 randomized
> patients, 240 (60%) were randomized to QuickSeal and 158 (40%) were
> randomized to Manual Compression. Of the patients randomized to
> QuickSeal, 145 (60%) were interventional and 95 (40 %) were
> diagnostic. Of the patients randomized to manual compression, 100
> (63%) were interventional and 58 (37%) were diagnostic.

# There were wide differences in the numbers of patients enrolled per investigational site, which is shown in detail in Table 3. 91% of the QuickSeal patients were enrolled at four centers. The QuickSeal device was used after diagnostic procedures at 5 sites. {#there-were-wide-differences-in-the-numbers-of-patients-enrolled-per-investigational-site-which-is-shown-in-detail-in-table-3.-91-of-the-quickseal-patients-were-enrolled-at-four-centers.-the-quickseal-device-was-used-after-diagnostic-procedures-at-5-sites. .unnumbered}

**Table 3. Randomized patient enrollment by site**

+-------+----------+-----------+-------+---------+------------+------+
| **S   | **Qui    |           |       | *       |            |      |
| ite** | ckSeal** |           |       | *Manual |            |      |
|       |          |           |       | Compre  |            |      |
|       |          |           |       | ssion** |            |      |
+-------+----------+-----------+-------+---------+------------+------+
|       | **Diag   | **Ther    | **To  | **Diagn | **The      | *    |
|       | nostic** | apeutic** | tal** | ostic** | rapeutic** | *Tot |
|       |          |           |       |         |            | al** |
|       | N=95     | N=145     | N=240 | N=58    | N=100      |      |
|       |          |           |       |         |            | N    |
|       |          |           |       |         |            | =158 |
+-------+----------+-----------+-------+---------+------------+------+
| **1** | 10       | 13        | 23    | 6       | 9          | 15   |
+-------+----------+-----------+-------+---------+------------+------+
| **2** | 22       | 23        | 45    | 15      | 15         | 30   |
+-------+----------+-----------+-------+---------+------------+------+
| **3** | 46       | 39        | 85    | 27      | 29         | 56   |
+-------+----------+-----------+-------+---------+------------+------+
| **4** | 4        |           | 4     | 1       |            | 1    |
+-------+----------+-----------+-------+---------+------------+------+
| **5** | 13       | 53        | 66    | 8       | 33         | 41   |
+-------+----------+-----------+-------+---------+------------+------+
| **6** |          | 11        | 11    | 1       | 8          | 9    |
+-------+----------+-----------+-------+---------+------------+------+
| **7** |          | 3         | 3     |         | 3          | 3    |
+-------+----------+-----------+-------+---------+------------+------+
| **8** |          | 1         | 1     |         | 1          | 1    |
+-------+----------+-----------+-------+---------+------------+------+
| **9** |          | 2         | 2     |         | 2          | 2    |
+-------+----------+-----------+-------+---------+------------+------+

> The study was designed as an equivalency trial for the 30-day primary
> safety endpoint of the combined rate of major complications, and as a
> superiority trial for the primary effectiveness endpoints of time to
> hemostasis (time from the end of the antecedent procedure to the time
> hemostasis is first observed), and time to ambulation (time from the
> end of the antecedent procedure to the time patient stands at bedside
> and [walks 10 feet]{.underline}). Major complications were defined as
> surgery or ultrasound-guided compression for vascular repair, bleeding
> requiring transfusion, groin-related infection requiring IV
> antibiotics or extended hospitalization.
>
> Secondary endpoints included: the time to hospital discharge (the time
> the antecedent procedure ends and the time the patient is discharged
> from the hospital), the time a patient is deemed eligible for
> discharge (the time the antecedent procedure ends and the time at
> which the patient is deemed eligible for discharge relative to the
> access site closure).

Additional endpoints include procedure success rate and device success
rate. Procedure success rate was defined as the number of patients in
which hemostasis was achieved with freedom from major complications vs.
the number attempted. Device success rate was defined as the number of
patients in which hemostasis was achieved using the QuickSeal device
with freedom from major complications.

# **Inclusion and Exclusion Criteria** {#inclusion-and-exclusion-criteria .unnumbered}

> Patients were enrolled if they met the following criteria: the patient
> was between 18 and 80 years of age; patient or guardian provided
> written informed consent, and; in a subgroup, patient agreed to an
> ultrasound examination of the femoral artery.

Patients were excluded from the investigation if they met any one of the
following criteria:

-   an arterial introducer sheath size of \>8F;

-   arterial closure site depth is \<3 cm or \>7.5 cm;

-   pre-existing autoimmune disease;

-   ipsilateral arterial site closure with QuickSeal device or manual
    compression within previous 6 weeks, or closure with another closure
    device within 180 days;

-   pregnant or lactating;

-   significant bleeding or platelet disorders including
    Thrombocytopenia (with \<100,000 platelet count), Von Willebrand's
    disease, anemia (Hgb \<10 gm/dl, Hct \<30) and thrombasthenia;

-   uncontrolled hypertension (blood pressure not controllable to
    \<170/100 mm Hg);

-   Bleeding pre- or post-sheath removal;

-   Elevated ACT levels in the manual compression group \>180 seconds,
    and in the QuickSeal group of \>300 seconds for patients not
    receiving GP IIb/IIIa platelet inhibitors and \>250 seconds for
    patients receiving GP IIb/IIIa platelet inhibitors.

#  **Methodology** {#methodology .unnumbered}

> The following methodology was used at each of the investigational
> sites:

-   Informed consent and baseline medical histories were obtained prior
    to the catheterization procedure.

-   Sheath removal was based on ACT level. Sheaths were removed in the
    Manual Compression group when the ACT level was [\<]{.underline}180
    seconds. Sheaths were removed in the QuickSeal group when the ACT
    level was [\<]{.underline} 300 seconds for patients not receiving GP
    IIb/IIIa platelet inhibitors, and [\<]{.underline}250 seconds for
    patients receiving GP IIb/IIIa platelet inhibitors.

-   The times when hemostasis, ambulation, discharge and eligible for
    hospital discharge occurred were recorded and the elapsed times to
    hemostasis, ambulation, hospital discharge and eligible for
    discharge were calculated from the end of the antecedent diagnostic
    or interventional procedure.

-   Patients were followed in the hospital and at the 30-day follow
    clinical evaluation for evidence of major complications or other
    vascular complications. Femoral artery ultrasounds were performed at
    the follow-up visit on 221 patients for evidence of pseudoaneurysms
    and arterio-venous (AV) fistulae.

# **Study Population** {#study-population .unnumbered}

There was no significant difference between the two randomized groups
with respect to age, risk factors, peri-procedural medications,
arteriotomy depth, or blood pressure.

> **Table 4. Patient Characteristics**

  --------------- --------- ------------ ------------ -------------- -------------- ---------------- ------------------
                  **Age**   **Height**   **Weight**   **Peripheral   **Diabetes**   **Claudication   **Hypertension**
                                                      vascular                      and/or no distal 
                                                      disease**                     pulse**          

  **QuickSeal**   62        171cm        88 kg        25%            32%            26%              45%

  **Control**     61        171cm        83 kg        24%            32%            23%              44%
  --------------- --------- ------------ ------------ -------------- -------------- ---------------- ------------------

[Treatment variables]{.underline}

[Access site]{.underline} -- right femoral artery in 197 (82%) device
and 133 (84%) control

[GP IIb/IIIa inhibitor use]{.underline} -- total of 96 patients

53 device or 22%

43 control or 27%

[Heparin]{.underline} -- 248 (62%) of the randomized

146 (61%) device

102 (65%) control

**Table 5.**

ACT at time of sheath pull

+-----------------------+-----------+-----------+-----------+-----------+
|                       | ##  *     |           | ##  **C   |           |
|                       | *Device** |           | ontrol**  |           |
+-----------------------+-----------+-----------+-----------+-----------+
|                       | **Range** | **Average | **Range** | **Average |
|                       |           | (SD)**    |           | (SD)**    |
+-----------------------+-----------+-----------+-----------+-----------+
| **Diagnostic          | 94-298    | 141.1     | 87-186    | 134.1     |
| procedure**           |           | (36.6)    |           | (24.6)    |
+-----------------------+-----------+-----------+-----------+-----------+
| **Interventional      | 104-300   | 217.2     | 114-299   | 160.9     |
| procedure**           |           | (48.8)    |           | (24.8)    |
+-----------------------+-----------+-----------+-----------+-----------+
| **Overall**           | 94-300    | 187.0     | 87-299    | 150.6     |
|                       |           | (57.9)    |           | (27.9)    |
+-----------------------+-----------+-----------+-----------+-----------+

Arterial sheath sizes were comparable between arms, as seen in Table 6.

## Table 6. Sheath size

  ----------------------- ----------------------- -----------------------
                          **Device**              **Control**

  **5Fr**                 26%                     23%

  **6Fr**                 39%                     41%

  **7Fr**                 13%                     15%

  **8Fr**                 23%                     20%
  ----------------------- ----------------------- -----------------------

# **Gender Bias Analysis** {#gender-bias-analysis .unnumbered}

> A higher number of male patients were enrolled in the study (65%) male
> vs. (35%) female, which is a reflection of the general referral
> pattern for patients undergoing interventional and diagnostic
> procedures. Both sexes had a statistically significant decrease in
> both time to hemostasis and time to ambulation.
>
> **Table 7. Primary effectiveness endpoint data**
>
> **Per sex**

+---------+------+-------+------+------+------+-------+------+------+
|         | **   |       |      |      | **   |       |      |      |
|         | Time |       |      |      | Time |       |      |      |
|         | to   |       |      |      | to   |       |      |      |
|         | he   |       |      |      | am   |       |      |      |
|         | most |       |      |      | bula |       |      |      |
|         | asis |       |      |      | tion |       |      |      |
|         | (mi  |       |      |      | (    |       |      |      |
|         | nute |       |      |      | hour |       |      |      |
|         | s)** |       |      |      | s)** |       |      |      |
+---------+------+-------+------+------+------+-------+------+------+
|         | **Di |       | **In |      | **Di |       | **In |      |
|         | agno |       | terv |      | agno |       | terv |      |
|         | stic |       | enti |      | stic |       | enti |      |
|         | c    |       | onal |      | c    |       | onal |      |
|         | athe |       | c    |      | athe |       | c    |      |
|         | teri |       | athe |      | teri |       | athe |      |
|         | zati |       | teri |      | zati |       | teri |      |
|         | on** |       | zati |      | on** |       | zati |      |
|         |      |       | on** |      |      |       | on** |      |
+---------+------+-------+------+------+------+-------+------+------+
|         | **   | *     | **   | **C  | **   | *     | **   | **c  |
|         | Devi | *Cont | Devi | ontr | Devi | *Cont | Devi | ontr |
|         | ce** | rol** | ce** | ol** | ce** | rol** | ce** | ol** |
+---------+------+-------+------+------+------+-------+------+------+
| **Men** | 60   | 31    | 96   | 71   | 60   | 31    | 96   | 71   |
|         |      |       |      |      |      |       |      |      |
| n       | 15   | 31    | 15   | 175  | 1.4  | 5.5   | 4.3  | 10   |
|         |      |       |      |      |      |       |      |      |
| median  | 17.4 | 34.3  | 20   | 203  | 2.3  | 5.8   | 5.7  | 11.7 |
|         |      |       |      |      |      |       |      |      |
| mean    | 5-48 | 5-71  | 5    | 10   | .9-  | 4.    | 1.1- | 4.3- |
|         |      |       | -167 | -936 | 16.2 | 1-8.9 | 21.5 | 22.3 |
| range   |      |       |      |      |      |       |      |      |
+---------+------+-------+------+------+------+-------+------+------+
| **      | 35   | 27    | 49   | 29   | 35   | 27    | 49   | 29   |
| Women** |      |       |      |      |      |       |      |      |
|         | 16   | 28.5  | 15   | 1    | 1.5  | 6.2   | 4.4  | 9.4  |
| n       |      |       |      | 27.5 |      |       |      |      |
|         | 16.2 | 33.5  | 19   |      | 2.4  | 6     | 9.25 | 12.2 |
| median  |      |       |      | 149  |      |       |      |      |
|         | 5-30 | 13-85 | 6-82 |      | 1-9  | 4.    | 1.1- | 6.2- |
| mean    |      |       |      | 16   |      | 2-9.9 | 94.1 | 24.6 |
|         |      |       |      | -734 |      |       |      |      |
| range   |      |       |      |      |      |       |      |      |
+---------+------+-------+------+------+------+-------+------+------+

# **Safety Data** {#safety-data .unnumbered}

> A summary of the adverse events (complications) experienced by
> patients enrolled in the QuickSeal Femoral Arterial Closure System
> clinical investigation is reported in Table 1. Major complications
> were experienced by 3 (1.3%) of 240 patients randomized to the
> QuickSeal device compared to 1 (0.6%) of the 158 patients randomized
> to Manual Compression.
>
> In 2 (0.8%) of the QuickSeal cases the Depth Marker went beyond the
> arteriotomy failing to measure the depth of the arteriotomy. In each
> case the procedure was successfully converted to manual compression
> prior to utilizing the QuickSeal delivery system with no
> complications. One (0.4%) of the QuickSeal cases was identified as a
> device failure for not achieving hemostasis. The procedure was
> converted to Manual Compression and a small (\< 6 cm) hematoma
> developed with no further complications. Device malfunctions were not
> associated with any risk of major complications as compared to all
> other QuickSeal-treated patients.
>
> No deaths were determined to be device-related. One death occurred in
> the QuickSeal arm during the 30-day follow-up period and was reported
> as not associated with the arterial access site closure.

# **Effectiveness Data** {#effectiveness-data .unnumbered}

> In both the diagnostic and interventional groups, use of the QuickSeal
> resulted in statistically significant decreases in time to hemostasis,
> time to ambulation, and the time a patient is deemed eligible for
> hospital discharge as compared to Manual Compression (Tables 2 and 3).
> In the diagnostic group there was a statistically significant decrease
> in time to actual discharge.

######## Table 2: Overall Effectiveness Table

+-------------------+---------+---------+----------+---------+-------+
|                   | **Quic  |         | **Manual |         | *     |
|                   | kSeal** |         | Compr    |         | *p-va |
|                   |         |         | ession** |         | lue** |
|                   | n=240   |         |          |         |       |
|                   |         |         | n=158    |         |       |
+-------------------+---------+---------+----------+---------+-------+
|                   | **Mean  | **M     | **Mean   | **M     |       |
|                   | (SD)**  | edian** | (SD)**   | edian** |       |
+-------------------+---------+---------+----------+---------+-------+
| **Time to         | 18.5    | 15.0    | 131.6    | 67.5    | \<    |
| Hemostasis        | (14.4)  |         |          |         | 0.001 |
| (min)**           |         |         | (159.2)  |         |       |
+-------------------+---------+---------+----------+---------+-------+
| **Time to         | 5.1     | 4.2     | 9.6      | 5.1     | \<    |
| Ambulation        |         |         |          |         | 0.001 |
| (hours)**         | (8.2)   |         | (5.1)    |         |       |
+-------------------+---------+---------+----------+---------+-------+
| **Time to         | 6.6     | 4.9     | 15.4     | 9.0     | \<    |
| Discharge         |         |         |          |         | 0.001 |
| (hours)**         | (8.3)   |         | (58.1)   |         |       |
|                   |         |         |          |         |       |
| **Eligible**      |         |         |          |         |       |
+-------------------+---------+---------+----------+---------+-------+
| **Time to         | 26.2    | 20.6    | 36.3     | 22.2    | 0.006 |
| Discharge**       |         |         |          |         |       |
|                   | (43.7)  |         | (81.3)   |         |       |
| **(hours)**       |         |         |          |         |       |
|                   |         |         |          |         |       |
| **Actual**        |         |         |          |         |       |
+-------------------+---------+---------+----------+---------+-------+
| **Device Success  | 232/240 |         | N/A      |         | N/A   |
| (a)**             | (96.7%) |         |          |         |       |
+-------------------+---------+---------+----------+---------+-------+
| **Procedure       | 235/240 |         | 157/158  |         | 0.409 |
| Success (b)**     | (97.9%) |         | (99.4%)  |         |       |
+-------------------+---------+---------+----------+---------+-------+

> \(a\) Device failure rate was defined as the number of patients in
> which hemostasis was not achieved using the QuickSeal device or a
> major complication occurred.
>
> \(b\) Procedure failure rate was defined as the number of patients in
> which hemostasis was not achieved, or a major complication occurred.

The number of patients is less than the total number of patients studied
due to missing data for some patients.

There were no malfunctioning QuickSeal devices.

######### Table 3: Effectiveness Table by procedure type

+----------+---------+-----------+------+---------+-----------+------+
|          | **Diagn |           |      | **In    |           |      |
|          | ostic** |           |      | tervent |           |      |
|          |         |           |      | ional** |           |      |
+----------+---------+-----------+------+---------+-----------+------+
|          | **Quic  | **Manual  | **p  | **Quic  | **Manual  | **p  |
|          | kSeal** | Comp      | -val | kSeal** | Comp      | -val |
|          |         | ression** | ue** |         | ression** | ue** |
+----------+---------+-----------+------+---------+-----------+------+
|          | Mean    | Mean (SD) |      | Mean    | Mean (SD) |      |
|          | (SD)    |           |      | (SD)    |           |      |
|          |         | *         |      |         | *         |      |
|          | **M     | *Median** |      | **M     | *Median** |      |
|          | edian** |           |      | edian** |           |      |
|          |         | Range     |      |         | Range     |      |
|          | Range   |           |      | Range   |           |      |
+----------+---------+-----------+------+---------+-----------+------+
| **Time   | 17      | 33.9      | \<0  | 19.5    | 187.8     | \<0  |
| to       | (7.8)   | (17.9)    | .001 | (17.4)  | (176.5)   | .001 |
| He       |         |           |      |         |           |      |
| mostasis | **15**  | **29**    |      | **15**  | **176.5** |      |
| (min)**  |         |           |      |         |           |      |
|          | 5-48    | 5-85      |      | 5-167   | 10-936    |      |
+----------+---------+-----------+------+---------+-----------+------+
| **Time   | 2.3     | 5.87      | \<0  | 6.9     | 11.8      | \<0  |
| to       | (2.2)   | (1.34)    | .001 | (10)    | (5.2)     | .001 |
| Am       |         |           |      |         |           |      |
| bulation | **1.5** | **5.8**   |      | **4.4** | **10**    |      |
| (        |         |           |      |         |           |      |
| hours)** | 0       | 4.1-9.9   |      | 1       | 4.3-24.6  |      |
|          | .9-16.2 |           |      | .1-94.1 |           |      |
+----------+---------+-----------+------+---------+-----------+------+
| **Time   | 4.0     | 6.6 (1.4) | \<0  | 8.3     | 20.4      | \<0  |
| to       | (3.9)   |           | .001 | (9.9)   | (72.6)    | .001 |
| D        |         | **6.4**   |      |         |           |      |
| ischarge | **3.2** |           |      | **6.2** | **11.4**  |      |
| (        |         | 4.6-10.9  |      |         |           |      |
| hours)** | 1       |           |      | 1       | 4.5-733.3 |      |
|          | .1-27.2 |           |      | .1-94.1 |           |      |
| **El     |         |           |      |         |           |      |
| igible** |         |           |      |         |           |      |
+----------+---------+-----------+------+---------+-----------+------+
| **Time   | 22.7    | 24.1      | \<0  | 28.5    | 43.5      | 0    |
| to       | (50.6)  | (42.9)    | .001 | (38.6)  | (96.4)    | .096 |
| Dis      |         |           |      |         |           |      |
| charge** | **4.3** | **7.1**   | \    | *       | **23.3**  |      |
|          |         |           | (a\) | *22.7** |           |      |
| **(      | 1.      | 4.6-213.7 |      |         | 6.5-890.3 |      |
| hours)** | 8-298.8 |           |      | 3.      |           |      |
|          |         |           |      | 1-436.1 |           |      |
| **       |         |           |      |         |           |      |
| Actual** |         |           |      |         |           |      |
+----------+---------+-----------+------+---------+-----------+------+

> \(a\) P-Value is based on Wilcoxon Rank Sum Test. The time to
> discharge results for the diagnostic group are skewed to high values,
> as evidenced by the large difference between the mean and the median
> in both treatment groups.  While the range for the
> QuickSeal diagnostic patients is 1.8-298.8 hours, 81.5% (75/92) of
> patients were discharged within 24 hours and 91.3% (84/92) of patients
> were discharged within 72 hours.  Similarly, in the manual compression
> group, the range was 4.6-213.7 hours, with 80.7% (46/57) of patients
> being discharged within 24 hours and 91.2% (52/57) of patients being
> discharged within 72 hours.  The skewed nature of this data
> necessitates the use of a non-parametric test, such as the Wilcoxon
> Rank Sum Test used above.  This test is highly significant (p\<0.001),
> which reflects the large difference in median time to discharge
> between the two groups (4.3 hours for QuickSeal versus 7.1 hours for
> manual compression).
>
> Time to hemostasis is defined as the interval (in minutes) between the
> time the interventional or diagnostic procedure ends and the time at
> which hemostasis is achieved. Hemostasis is defined as the absence of
> bleeding and the absence of a palpable hematoma at the access site.
>
> Time to ambulation is defined as the interval (in hours) between the
> time the interventional or diagnostic procedure ends and the time at
> which the patient walks 10 feet.
>
> Time to discharge (eligible) the interval (in hours) between the time
> the interventional or diagnostic procedure ends, and the time the
> patient is deemed eligible for discharge from the hospital based
> solely on the hemostasis results.
>
> Time to discharge (actual) the interval (in hours) between the time
> the interventional or diagnostic procedure ends, and the time the
> patient was actually discharged from the hospital.

![](media/image4.wmf)

# **Conclusions Drawn from Studies**

> Results of the in vitro, animal studies, and clinical investigations
> provide valid scientific evidence and reasonable assurance that the
> QuickSeal Femoral Arterial Closure System is safe and effective when
> used in accordance with its labeling. The safety of the device has
> been demonstrated by the fact that the incidence of major
> complications in the randomized clinical investigation was equivalent
> for both treatment arms (QuickSeal Femoral Arterial Closure System
> procedure compared to Manual Compression therapy). The effectiveness
> of the QuickSeal Femoral Arterial Closure System was demonstrated by a
> significant reduction in the time to hemostasis and time to ambulation
> in both diagnostic and interventional patients treated with QuickSeal
> compared to those treated with standard Manual Compression. The
> effectiveness of the QuickSeal Femoral Arterial Closure System was
> also demonstrated by a significant reduction in time to hospital
> discharge after a diagnostic cardiac catheterization and the time a
> patient is deemed eligible for hospital discharge in patients treated
> with the QuickSeal Femoral Arterial Closure System compared to those
> treated with standard Manual Compression.

# **Panel Recommendations**

> In accordance with the provisions of section 515(c)(2) of the act as
> amended by the Safe Medical Devices Act of 1990, this PMA was not
> referred to the Circulatory System Devices Panel, an FDA advisory
> committee, for review and recommendation because the information in
> this PMA substantially duplicates information previously reviewed by
> the panel.

#  {#section-3 .unnumbered}

#  {#section-4 .unnumbered}

# **FDA Decision**

#  {#section-5 .unnumbered}

# FDA issued a PMA approval letter to SUB-Q, Inc. on March 25, 2002.  {#fda-issued-a-pma-approval-letter-to-sub-q-inc.-on-march-25-2002. .unnumbered}

#  {#section-6 .unnumbered}

> The applicant's manufacturing facilities were inspected and found to
> be in compliance with the Quality Systems Regulation (21 CFR 820).

# **Approval Specification**

> Instructions for Use: See the labeling
>
> Hazards to Health from the use of the Device: See Indications,
> Contraindications, Warnings, Precautions, and Adverse Events section
> of the labeling.
>
> Post-approval Requirements and Restrictions: See approval order.