(401 days)
Not Found
No
The device description focuses on mechanical components and manual operation, with no mention of AI, ML, or image processing.
Yes
The device is intended to close punctures, incisions or ostomies in cardiac apical tissue, which is a direct treatment of a medical condition.
No
The device is indicated for soft tissue approximation of cardiac apical tissue to close punctures, incisions or ostomies during transcatheter valve replacement procedures. It is a therapeutic device, not a diagnostic one.
No
The device description clearly details physical components such as a delivery device, implant, handle, trigger, mechanical safety, anchors, suture, and knot pusher. It describes mechanical actions and deployment of physical materials into the body. There is no mention of software as a component or function of the device.
Based on the provided information, the Permaseal device is not an In Vitro Diagnostic (IVD).
Here's why:
- Intended Use: The intended use is for "soft tissue approximation of cardiac apical tissue during transcatheter valve replacement procedures." This describes a surgical procedure performed directly on the patient's tissue, not a test performed on a sample taken from the body.
- Device Description: The description details a mechanical device used to deploy anchors and suture to close a puncture or incision. This is a therapeutic/surgical device, not a diagnostic one.
- Lack of IVD Characteristics: The description does not mention any of the typical characteristics of an IVD, such as:
- Analyzing biological samples (blood, urine, tissue, etc.)
- Detecting or measuring substances in samples
- Providing information for diagnosis, monitoring, or screening
The Permaseal is a medical device used for a surgical procedure to close tissue. It does not perform any diagnostic function.
N/A
Intended Use / Indications for Use
The Permaseal is indicated for soft tissue approximation of cardiac apical tissue during transcatheter valve replacement procedures.
Product codes (comma separated list FDA assigned to the subject device)
PNQ
Device Description
The Permaseal device is composed of a delivery device and an implant that is deployed to facilitate access and closure. The deployment site is accessed via minimally invasive surgery or percutaneous surgery. The device is compatible with a 0.025" guide wire. The implant is designed to close punctures, incisions or ostomies in the cardiac apical tissue up to 30F, or 10mm in diameter.
The device features a handle designed to facilitate proper device placement and allow for singlehanded deployment of the implant. The handle contains a trigger that actuates the device and incorporates a mechanical safety. The handle functions as a tool to grip and position the device. It contains the actuating mechanism to control deployment of the anchor using a trigger mechanism. With the safety in the ON position, it prevents movement of the trigger and reduces the potential for accidental firing. The insertion tube extends from the handle and contains the implant. The insertion tube is 14cm long to ensure sufficient access to the target site.
The implant is composed of an array of eight polypropylene anchors connected by a 2-0 braided, coated polyester suture U.S.P. The suture is threaded through the eyelets of the eight anchors in a circular pattern and terminates in a surgical knot. The excess suture provided is referred to as the loop limb. The opening that is formed in the center of the implant is referred to as the 'operative window.' The knot is tightened at the end of the procedure by advancing the knot pusher toward the implant. The knot pusher is affixed to the insertion tube by the knot pusher retainer and is removed from the tube before the implant is deployed.
Upon release of the safety and actuation of the trigger, a spring-loaded pusher tube connected distally to 8 pusher pins is released, transmitting the force of the spring through the pusher pins to the anchors, simultaneously embedding the 8 anchors firmly into the tissue at the target site.
The anchors are deployed at a pre-determined depth with the sutures resting on the surface of the heart. Once deployed, the polyester suture and eight anchors create an 'operative window' in a pattern approximating that of a purse-string suture pattern. The anchors provide a secure attachment site for the suture that connects the multiple anchors together. The suture serves as a means to bring the incised tissue edges into apposition so as to close the puncture. Advancing the surgical knot in the suture with the knot pusher creates sufficient tension on the anchors to pull them and the tissue together so as to close punctures, incisions or otomies in the cardiac apical tissue up to 30F, or 10mm in diameter.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Cardiac apical tissue
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Bench Testing:
The Permaseal device functionality was assessed using two sets of bench testing: design verification and performance verification. These included evaluating packaging validation, sterilization validation, shelf life testing, environmental conditioning, package integrity, design verification testing (device weight, dimensional verification, color/appearance verification), device operation verification (trigger safety, guidewire compatibility, trigger pull force, safety disengagement force, inability to fire with engaged safety, anchor deployment depth), implant performance verification (accommodates intended sheath sizes, suture grip detachment, knot pusher functionality, suture knot functionality and slip force, anchor eyelet functionality under tension and axial pull force, anchor barb extraction), performance verification testing in porcine ex vivo hearts, anchor pull out test, and leakage test. All tests passed.
Animal Study:
Chronic Animal Study at 30 Days: Compared Permaseal to conventional mattress suture in a porcine model. All animals survived to the designated end point with no significant adverse clinical observations or procedural complications related to the test devices. Pathological changes were minimal and expected for this type of procedure.
Acute Investigational Analysis, in vivo testing of Permaseal configurations: Evaluated performance in an in vivo porcine model. Three separate deployments were completed in one animal with acceptable results.
Clinical Study (STASIS):
Study Type: Non-randomized, multi-center, prospective, open-label, observational safety and performance study.
Sample Size: 34 patients undergoing transcatheter aortic valve replacement (TA-TAVR). 31 patients included in effectiveness analysis.
Primary Effectiveness Endpoint: Rate of pulsatile bleeding requiring significant surgical intervention (more than one pledgeted suture) at discharge and at 30-day follow-up. Target was 15%.
Results Primary Effectiveness: 6.5% (2/31), meeting the primary effectiveness endpoint target.
Secondary Effectiveness Endpoints: Treatment parameters (procedure time, ease of use), and appearance of new hypo- or akinesis at 90 days and 12 months.
Results Secondary Effectiveness: TAVR Procedural Success 100%, Mortality (30-days) 0.0%, Myocardial Infarction (30-day) 0.0%, Stroke (30-day) 0.0%, Vascular Complications 2.9%, Conversion to Sternotomy 0.0%, New Permanent Pacemaker 12.1%, Procedure Time (min) 86.0 +/- 19.6, Need for Transfusion (>2 units) 8.8%, Hospital Stay 10.6 +/- 3.7. At 90 days, Mortality 3.1%, Myocardial Infarction 0.0%, Stroke 0.0%. One patient death due to non-cardiovascular causes reported at 37 days. No change in wall motion reported for any patient between screening and hospital discharge. At 90-day follow-up, some patients showed improvement or development of hypokinesis/akinesis.
Safety Endpoint: All adverse events (AEs) and serious adverse events (SAEs) during TA-TAVR and follow-up (30 days, 90 days, 12 months), defined by VARC 2.
Results Safety: No deaths, myocardial infarctions, or strokes for any patients during the 30-day follow-up period. This favorable safety profile was maintained at 90-days clinical follow-up. 33 SAEs reported, two device-related involving setting the pre-tied knot before achieving hemostasis, requiring extra sutures. These were addressed by additional training.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Primary Effectiveness: Rate of pulsatile bleeding requiring significant surgical intervention: 6.5% (2/31)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Not Found
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 870.4510 Apical closure device.
(a)
Identification. An apical closure device is a prescription device consisting of a delivery system and implant component that is used for soft tissue approximation of cardiac apical tissue during transcatheter valve replacement procedures.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The patient contacting materials must be evaluated to be biocompatible.
(2) Performance data must validate the sterility of the patient-contacting components of the device.
(3) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the labeled shelf life.
(4) Non-clinical performance testing data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(i) Consistent and reliable implant deployment;
(ii) Assessment of implant pull-out force; and
(iii) Sheath size compatibility with implant.
(5) In vivo evaluation of the device must demonstrate device performance, including device operation resulting in closure of the myocardial wound.
(6) Labeling must include the following:
(i) Detailed information explaining how the device operates;
(ii) Sheath size that device can accommodate;
(iii) Identification of the minimum myocardial wall thickness to ensure optimal device function; and
(iv) A shelf life.
0
DE NOVO CLASSIFICATION REQUEST FOR PERMASEAL
REGULATORY INFORMATION
FDA identifies this generic type of device as:
Apical Closure Device. An apical closure device is a prescription device consisting of a delivery system and implant component that is used for soft tissue approximation of cardiac apical tissue during transcatheter valve replacement procedures.
NEW REGULATION NUMBER: 21 CFR 870.4510
CLASSIFICATION: II
PRODUCT CODE: PNQ
BACKGROUND
DEVICE NAME: PERMASEAL
SUBMISSION NUMBER: DEN150029
DATE OF DE NOVO: JUNE 25, 2015
CONTACT: MICRO INTERVENTIONAL DEVICES, INC. 5 Caufield Pl. SUITE 102 NEWTOWN, PA 18940
REQUESTER'S RECOMMENDED CLASSIFICATION: II
INDICATIONS FOR USE
The Permaseal is indicated for soft tissue approximation of cardiac apical tissue during transcatheter valve replacement procedures.
LIMITATIONS
The sale, distribution and use of the Permaseal device is limited to prescription use onlv.
Limitations on the device use are also achieved through the following statements included in the Instructions for Use:
Contraindications:
- · Patients who are allergic to contrast agent.
1
- · Patients who are allergic to platelet inhibitor therapy.
- · Patients where a substantial risk of complications due to concomitant therapy, disease state or other condition exists.
- Patients whose target site for deployment has a myocardial wall thickness less than 10mm.
- · Tissue that has been compromised due to previous adverse events such as infarction.
- · Instances where excessive fat is present at the target site for deployment.
- · Procedures where sheath introducers or catheters of more than 30F in outer diameter are needed.
Warnings:
DO NOT use the Permaseal device if the sterile barrier of the packaging has previously been broken, damaged or if the contents of the package appear to be damaged or defective.
DO NOT handle the Permaseal device without ensuring the safety is in the ON position.
DO NOT look into the distal end of the device or point the device at another individual.
DO NOT use rapid pacing when deploying the Permaseal device for cardiac applications.
DO NOT deploy the device at the true apex.
DO NOT attempt to pass sheath introducers or catheters of more than 30F (10mm) in outer diameter through the "operative window" of the Permaseal implant.
DO NOT use the Permaseal device if the expiration date has elapsed, as either sterility or performance may be compromised.
PLEASE REFER TO THE LABELING FOR A MORE COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
DEVICE DESCRIPTION
The Permaseal device is composed of a delivery device and an implant that is deployed to facilitate access and closure. The deployment site is accessed via minimally invasive surgery or percutaneous surgery. The device is compatible with a 0.025" guide wire. The implant is designed to close punctures, incisions or ostomies in the cardiac apical tissue up to 30F, or 10mm in diameter.
The device features a handle designed to facilitate proper device placement and allow for singlehanded deployment of the implant. The handle contains a trigger that actuates the device and incorporates a mechanical safety. The handle functions as a tool to grip and position the device. It contains the actuating mechanism to control deployment of the anchor using a trigger mechanism.
2
With the safety in the ON position, it prevents movement of the trigger and reduces the potential for accidental firing. The insertion tube extends from the handle and contains the implant. The insertion tube is 14cm long to ensure sufficient access to the target site. The device handle and insertion tube can be viewed below in Figure 1.
Image /page/2/Figure/1 description: This image shows a diagram of a surgical tool with several labeled parts. The tool has a handle, a trigger, and a safety mechanism. The front of the tool has a guidewire channel, a suture slot, a knot pusher, a knot pusher retainer, and an insertion tube.
Figure 1. Permaseal™ Delivery System
The implant is composed of an array of eight polypropylene anchors connected by a 2-0 braided, coated polyester suture U.S.P, as seen in Figures 2 and 3. The suture was separately cleared to market through K021019.
Image /page/2/Figure/4 description: The image shows two figures, Figure 2 and Figure 3, with labels pointing to different parts of the figures. Figure 2, titled "Permaseal Implant", shows a circular structure with labels such as "Eight Polypropylene Anchors", "Operative Window", "One Coated, Braided Polyester Suture", "Loop Limb", and "Surgical Knot". Figure 3, titled "Anchor", shows a pointed structure with labels such as "Eyelet", "Flexible Shaft", "Barb", "Three Identical Barbs", and "Tip".
3
Image /page/3/Figure/0 description: The image shows a diagram of a surgical tool. The tool has several labeled parts, including an implant, knot, loop limb, knot pusher, suture grip, and score. The implant is a circular structure with small protrusions around its perimeter. The suture grip is located at the end of the tool.
Figure 4. Knot Pusher
The suture is threaded through the eyelets of the eight anchors in a circular pattern and terminates in a surgical knot. The excess suture provided is referred to as the loop limb. The opening that is formed in the center of the implant is referred to as the 'operative window.' The knot is tightened at the end of the procedure by advancing the knot pusher toward the implant. The knot pusher is shown in Figure 4. above. The knot pusher is affixed to the insertion tube by the knot pusher retainer and is removed from the tube before the implant is deployed.
Upon release of the safety and actuation of the trigger, a spring-loaded pusher tube connected distally to 8 pusher pins is released, transmitting the force of the spring through the pusher pins to the anchors, simultaneously embedding the 8 anchors firmly into the tissue at the target site. A properly deployed anchor is demonstrated in Figures 5 through 7, below.
Image /page/3/Figure/4 description: The image shows three diagrams of a medical device being deployed into the epicardium. The first diagram, labeled "Figure 5. Properly Deployed", shows the device fully inserted into the epicardium. The second diagram, labeled "Figure 6. Partially Deployed", shows the device partially inserted into the epicardium. The third diagram, labeled "Figure 7. Un-Deploy", shows the device not inserted into the epicardium.
Image /page/3/Figure/5 description: The image is a title that reads "Figure 5. Properly Deployed Anchors". The text is centered on the page. The font is a serif font.
Figure 6. Partially Deployed Anchors
Figure 7. Un-Deployed Anchors
The anchors are deployed at a pre-determined depth with the sutures resting on the surface of the heart. Once deployed, the polyester suture and eight anchors create an 'operative window' in a pattern approximating that of a purse-string suture pattern. The anchors provide a secure attachment site for the suture that connects the multiple anchors together. The suture serves as a means to bring the incised tissue edges into apposition so as to close the puncture. Advancing the surgical knot in the suture with the knot pusher creates sufficient tension on the anchors to pull them and the tissue together so as to close punctures, incisions or otomies in the cardiac apical tissue up to 30F, or 10mm in diameter.
4
SUMMARY OF NONCLINICAL/BENCH STUDIES
BIOCOMPATIBILITY/MATERIALS
The Permaseal implant is tissue contacting and the delivery system is a limited contacting, external communicating device that comes in contact with tissue.
The distal 10cm of the delivery system, including the implant, was tested to assess the biocompatibility of the delivery system. This was appropriate because all limited contact exposure materials are contained within the distal 10cm of the device. In accordance with ISO 10993-1 and relevant subparts, cytotoxicity, sensitization testing was performed to assess the delivery system.
The Permaseal implant was tested separately using the following biocompatibility tests: cvtotoxicity, intracutaneous reactivity, sensitization, material mediated pyrogenicity, acute systemic toxicity, hemolysis and bacteria reverse mutation. The implant did not require implantation, sub-chronic toxicity and chronic toxicity based on existing animal study data and OUS clinical data. Carcinogenicity testing was omitted considering that the suture is cleared and that there were no relevant concerns with the animal or clinical data reviewed as part of the de novo submission. An overview of the biocompatibility testing performed to evaluate the biocompatibility of Permaseal is provided in Table 1. The Permaseal implant and delivery system were determined to be biocompatible based on these tests.
| Test | Purpose | Results |
|---|---|---|
| Delivery System | ||
| Cytotoxicity | ||
| MEM Elution Using L-929 Mouse | ||
| Fibroblast Cells (GLP) | Assessment of biological reactivity of | |
| mammalian cell cultures following incubation | ||
| with test device extracts | Non-cytotoxic | |
| Sensitization | ||
| Guinea Pig Maximization | ||
| Sensitization Test (GLP) | Determine the potential for the test device | |
| extract to elicit contact dermal allergenicity | Non-sensitizing | |
| Irritation | ||
| Intracutaneous Irritation Test | ||
| (GLP) | Assess potential of the device to produce | |
| irritation following a single intradermal injection | ||
| of specific extracts prepared from a test device | Non-irritant | |
| Hemolysis | ||
| Hemolysis Assay - Direct Contact | ||
| Method (GLP) | Evaluate the hemolytic potential of test articles | Non-hemolytic |
| Systemic Toxicity | ||
| Acute Systemic Injection Test | ||
| (GLP) | Screen test article extracts or solutions for | |
| potential toxic effects as a result of a single-dose | ||
| systemic injection in mice. | Non-toxic | |
| Pyrogenicity | ||
| Materials Mediated Rabbit | ||
| Pyrogen (USP and GLP) | Evaluate the test device extract for leachates that | |
| have the potential to induce material-mediated | ||
| pyrogenicity following a single dose injection | Not pyrogenic | |
| Implant | ||
| Cytotoxicity (In Vitro | ||
| Cytotoxicity Study) | Evaluate an extract of a test article for | |
| cytotoxicity to mammalian cells in culture | Non-cytotoxic | |
| Sensitization (Maximization | ||
| Sensitization Study) | Evaluate the potential of test article to cause | |
| delayed dermal contact sensitization | Non-sensitizing |
Table 1. Biocompatibility Tests for Permaseal Delivery System and Implant
5
| Test | Purpose | Results |
|---|---|---|
| Irritation (Intracutaneous | ||
| Reactivity Study) | Evaluate the local dermal irritation of a test | |
| article extract following intracutaneous injection | ||
| in rabbits | Non-irritant | |
| Acute Systemic Toxicity | ||
| (Systemic Toxicity Study) | Evaluate acute systemic toxicity of test article | |
| extract following injection in mice | Non-toxic | |
| Pyrogenicity (Material Mediated | ||
| (USP and GLP)) | Determine whether an extract of the test article | |
| induced a pyrogenic response following | ||
| intravenous injection in rabbits | Non-pyrogenic | |
| Hemocompatibility (Hemolysis – | ||
| Direct (GLP)) | Evaluate the potential to cause hemolysis | Non-hemolytic |
| Genotoxicity (AMES Assay | ||
| Bacterial Reverse Mutation) | Evaluate the mutagenic potential of the device | |
| test article by measuring its ability to induce | ||
| DNA reverse mutations in S. typhimurium and | ||
| E. coli in the presence and absence of | ||
| microsomal enzymes | Non-mutagenic |
SHELF LIFE/STERILITY
Packaging validation, sterilization validation and shelf life testing were performed to evaluate the Permaseal device, as summarized in Table 2 below. The Permaseal device was determined to have a 1-year shelf life, based on the real time aging.
Table 2. Packaging Validation, Sterilization Validation and Shelf Life Testing Overview for the
| Permaseal | |||
|---|---|---|---|
| Test | Purpose | Acceptance Criteria | Results |
| Packaging | |||
| Validation | Produce objective evidence | ||
| that the package obtained | |||
| using the design for the | |||
| individual package of | |||
| Micro Interventional | |||
| Devices (MID) meets the | |||
| requirements of MID, the | |||
| manufacturer's drawings | |||
| and product specifications | |||
| when the package is made. | Seal Visual Inspection: No burns, | ||
| channels, voids, pleats or foreign | |||
| matter |
Peel Samples: Minimum peel force 1
lb/in
Burst Samples: Minimum burst
values recorded
Bubble Samples: No seal leaks/seal
bubbles accepted
Dye Samples: No complete seal dye
penetration accepted | All tests passed |
6
| Test | Purpose | Acceptance Criteria | Results |
|---|---|---|---|
| Sterilization | |||
| Validation | Evaluate the sterilization | ||
| procedure for the | |||
| Permaseal device and the | |||
| ability to sterilize the | |||
| device according to the pre- | |||
| identified criteria, including | |||
| achieving a Sterility | |||
| Assurance Level of 10-6 | Bioburden: b(4) |
Bacteriostasis/Fungistasis: Neither
acceptable
EO Residual: Total recoverable mass
b(
Bacterial Endotoxin: b(4)
EtO Acceptable Limit: b( | All tests passed |
| Shelf Life | Evaluate the impact of one
year real time aging on the
Permaseal device | Visual and Functional assessments
(i.e., successful ex-vivo device
deployment) at baseline and one year | All visual
inspections and
functional tests
passed |
| Environmental
Conditioning
and Package
Integrity | Evaluate the Permaseal
devices after being
subjected to a range of
temperatures, humidity and
simulated distribution
testing | Verification testing, performance
testing (i.e., successful deployment
in porcine heart, compatibility with
sheath, functionality of suture grip,
knot pusher, knot and anchor
eyelets), packaging verification
testing, average peel force >1.0lbf/in | All tests passed,
any deviations
appropriately
explained |
| Package
Integrity | Demonstrate that the
Permaseal device
packaging will provide
sufficient protection suchdevice and package
integrity are not
compromised as a result of
typical package handling
processes | Seal Peel: No irregularities or
delamination of the seals observed,
peel strength greater than 1 lbf/in
Dye Penetration: No dye penetrates
through seal | All tests passed |
| Test | Purpose | Results | |
| Design Verification
Testing | Ensure that the design meets the design inputs as
defined in the Product Performance
Specifications for the Permaseal | All acceptance criteria met,
any deviations
appropriately justified | |
| Device Weight | Ensure that the device weight meets specification | All passed | |
| Dimensional
Verification | Ensure that the following measurements meet
specification:
- Overall device length, height, width
- Insertion tube length, diameter
- Anchor overall length
- Knot location on suture | All passed | |
| Color/Appearance
Verification | Ensure that the handle, insertion tube and safety
meet color/ appearance specifications | All passed | |
| Device Operation
Verification | Ensure that the device operates to specification
by evaluating the following: - Trigger safety functionality
- Guidewire compatibility
- Trigger pull force
- Safety disengagement force
- Inability to fire with an engaged safety
- Anchor deployment depth using the
delivery system | All passed | |
| Implant
Performance
Verification | Evaluate if the implant meets the following
criteria: - Accommodates intended sheath sizes
- Suture grip detaches from knot pusher
- Knot pusher functionality
- Suture knot functionality and slip force
- Anchor eyelet functionality under
tension and axial pull force - Anchor barb extraction from tissue
without breakage - Peak anchor insertion force | All passed | |
| Performance Verification
Testing | Conduct functional performance verification
testing in porcine ex vivo hearts | All criteria passed | |
| Anchor Pull Out
Test | No anchor pull out from the tissue at a tensioning
force of 1N | Passed, no anchor pull out | |
| Leakage Test | No leakage of solution shall occur at a pressure
of 180 mmHg | Passed, no leakage | |
PERFORMANCE TESTING - BENCH
The Permaseal device functionality was assessed using two sets of bench testing, including design verification and a performance verification test, as described in Table 3.
7
| Table 3. Bench Testing Overview | ||||
|---|---|---|---|---|
| -- | -- | -- | -- | --------------------------------- |
The Permaseal also underwent verification of component materials, packaging configuration and labeling verification. These verifications demonstrated the conformance of the packaging, labeling and component material to predetermined acceptance criteria, thus further supporting the device safety profile.
8
PERFORMANCE TESTING - ANIMAL
The Permaseal was rigorously evaluated under a chronic animal study comparing the Permaseal device to conventional mattress suture in a porcine model at 30 days as summarized in Table 4. The device was also assessed using an investigational analysis, specifically in vivo testing of the Permaseal configuration with the molded polypropylene anchors.
| Test | Purpose | Acceptance Criteria | Results |
|---|---|---|---|
| Chronic | |||
| Animal Study | |||
| at 30 Days | Demonstrate the | ||
| performance of the | |||
| Permaseal Device | |||
| (test article) to | |||
| traditional mattress | |||
| suture closure | |||
| b(4) | |||
| cardiovascular | |||
| surgical applications | Success in facilitating the | ||
| transapical access following a | |||
| transapical puncture of the | |||
| left ventricle in a simulated | |||
| transcatheter heart valve | |||
| implantation procedure | |||
| acutely and with respect to | |||
| wound healing chronically | |||
| (30 day survival) in a porcine | |||
| model | b(4) | ||
| all animals | |||
| survived to the designated | |||
| end point with no | |||
| significant adverse clinical | |||
| observations or procedural | |||
| complications related to the | |||
| test devices. Pathological | |||
| changes were minimal and | |||
| expected for this type of | |||
| procedure. | |||
| Acute | |||
| Investigational | |||
| Analysis, in vivo | |||
| testing of | |||
| Permaseal | |||
| configurations | Evaluate the | ||
| performance of the | |||
| Permaseal in an in | |||
| vivo porcine model | Assessment of performance | ||
| of the polypropylene anchors, | |||
| the interaction between the | |||
| suture and the insertion tube | |||
| during deployment, the | |||
| tensioning process to achieve | |||
| wound closure, the | |||
| performance of implant | |||
| deployment, passage of | |||
| transapical sheath and | |||
| achieving hemostasis | Three separate deployments | ||
| were completed in one | |||
| animal with acceptable | |||
| results. |
Table 4. Nonclinical Animal Study Testing Overview
SUMMARY OF CLINICAL INFORMATION
The STASIS (Secure Transapical Access and Closure) study, a non-randomized, multi-center, prospective, open-label, observational safety and performance study, was conducted to evaluate the Permaseal device. There were 34 patients undergoing transcatheter aortic valve replacement (TA-TAVR) at five clinical sites in Germany and the Netherlands. Table 5 details the population demographics and baseline characteristics of the patients in STASIS.
9
| Number of subjects enrolled | 34 |
|---|---|
| Age | 79.4 +/- 7 |
| Female | 47.1% |
| Hypertension | 88.2% |
| Coronary artery disease | 70.6% |
| Mitral valve disease | 41.2% |
| COPD | 11.8% |
| Coagulopathy | 2.9% |
| Cancer | 11.8% |
Table 5. STASIS Demographics and Baseline Characteristics
The STASIS endpoints were as follows:
Primary Effectiveness Endpoint:
Rate of pulsatile bleeding requiring significant surgical intervention (more than one pledgeted suture) at discharge and at 30-day follow-up. The literature derived performance goal was 15%.
Secondary Effectiveness Endpoint:
Treatment parameters that include procedure time, any reported assessment of ease of use, and the appearance of new hypo- or akinesis at 90 days and 12 months.
Safety Endpoint:
All adverse events (AEs) and serious adverse events (SAEs) occurring during the TA-TAVR procedure and follow-up periods of 30 days, 90 days and 12 months. The safety analysis involved reporting of all SAEs and AEs as well as their severity and relation to the Permaseal device and transapical approach. Valve Academic Research Consortium (VARC) 2 (J Thorac Cardiovasc Surg 2013;145:6-23) definitions were used.
Results
Primary Effectiveness:
The rate of pulsatile bleeding requiring more than one pledgeted suture at hospital discharge and 30-day follow-up was 6.5% (2/31), meeting the primary effectiveness endpoint target. Of the 34 total patients in the STASIS study, only 31 patients were included in the effectiveness analysis. One of the excluded patients was a roll-in, while the remaining two patients were excluded due to protocol violations.
Secondary Effectiveness:
The results of STASIS with respect to secondary endpoints and clinical outcomes are provided in Table 6 and Table 7.
10
| Number of Subjects | 34 |
|---|---|
| TAVR Procedural Success | 100% |
| Mortality (30-days) | 0.0% |
| Myocardial Infarction (30-day) | 0.0% |
| Stroke (30-day) | 0.0% |
| Vascular Complications | 2.9% |
| Conversion to Sternotomy | 0.0% |
| New Permanent Pacemaker | 12.1% |
| Procedure Time (min) | 86.0 +/- 19.6 |
| Need for Transfusion (>2 units) | 8.8% |
| Hospital Stay | 10.6 +/- 3.7 |
Table 6. STASIS Procedural Secondary Endpoints and 30-Day Clinical Outcomes
| Table 7. STASIS Clinical Outcomes and Secondary Endpoints at 90 Days | |||||
|---|---|---|---|---|---|
| Number of Subjects | 3 |
|---|---|
| Mortality | 3.1% |
| Myocardial Infarction | 0.0% |
| Stroke | 0.0% |
One patient death due to non-cardiovascular causes subsequent to orthopedic surgery was reported prior to 90-day follow-up. There was no change in wall motion reported for any patient between screening and hospital discharge. At the 90-day follow-up one patient improved from moderate hypokinesis to normal and one improved from moderate to mild hypokinesis. One patient developed mild hypokinesis and one developed moderate hypokinesis. One patient with moderate hypokinesis at screening was reported akinetic at 90-day follow-up.
Safety Endpoints:
There were no deaths, myocardial infarctions or strokes for any patients during the 30-day follow-up period. This favorable safety profile was maintained at 90-days clinical follow-up. One patient died at day 37 due to pulmonary embolism subsequent to a hip replacement surgery. This death was determined to not be related to either the procedure or device.
Thirty-three (33) SAEs were reported during the study, of which two were considered devicerelated. The two device-related SAEs involved setting the pre-tied knot before achieving hemostasis, requiring the addition of extra sutures. These events occurred at one site, early in the study, indicating a need for additional training on the Permaseal IFU, which was implemented and no further device-related SAEs were reported.
LABELING
Labeling provided for the Permaseal includes Instructions for Use and packaging labels. The labeling provided satisfies the requirements of 21 CFR § 801.109 Prescription devices, and
11
includes information regarding specifications, instructions for use, contraindications, warnings, and cautions, as well as a prescription statement.
Important components of the labeling include:
- Contraindication to exclude patients with myocardial wall thickness less than 10mm, due l to the risk of myocardial wall perforation; and
- ー Detailed instructions explaining each step of Permaseal use
RISKS TO HEALTH
Table 8 identifies the risks to health that may be associated with use of the Apical Closure Device and the measures necessary to mitigate these risks.
| Identified Risk | Mitigation Measure |
|---|---|
| Infection | Sterilization Validation |
| Shelf Life Testing | |
| Labeling | |
| Adverse Tissue Reaction | Biocompatibility Evaluation |
| In vivo Performance Testing | |
| Bleeding | |
| • At ventricular puncture or anchor | |
| deployment sites | Non-clinical Performance Testing |
| In vivo Performance Testing | |
| Labeling | |
| Tissue Damage | |
| • Apical tearing | |
| • Myocardial tearing (local or diffuse) | Non-clinical Performance Testing |
| In vivo Performance Testing | |
| Labeling | |
| Training | |
| New Hypokinesia or Akinesis of Apex | In vivo Performance Testing |
| Labeling | |
| Thromboemboli and Full Thickness Injury | In vivo Performance Testing |
| Labeling | |
| Training | |
| Pericardial Tamponade | In vivo Performance Testing |
| Labeling |
Table 8. Identified Risks to Health and Mitigation Measures
SPECIAL CONTROLS
In combination with the general controls of the FD&C Act, the Apical Closure Device is subject to the following special controls:
-
- The patient contacting materials must be evaluated to be biocompatible.
-
- Performance data must validate the sterility of the patient-contacting components of the device.
-
- Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the labeled shelf life.
-
- Non-clinical performance testing data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
12
- Consistent and reliable implant deployment; a.
- b. Assessment of implant pull-out force; and
- c. Sheath size compatibility with implant.
-
- In vivo evaluation of the device must demonstrate device performance, including device operation resulting in closure of the myocardial wound.
-
- Labeling must include the following:
- a. Detailed information explaining how the device operates;
- b. Sheath size that device can accommodate;
- c. Identification of the minimum myocardial wall thickness to ensure optimal device function; and
- d. A shelf life.
BENEFIT/RISK DETERMINATION
The risks of the device are based on nonclinical laboratory tests, animal studies, and data collected in a clinical study as described above. In the STASIS clinical study, SAEs occurring in the population included vascular complications (2.9%) and new permanent pacemaker (related to TAVR placement) (12.1%) at 30 days post-procedure. There were no deaths, myocardial infarctions, or strokes for any patients during the 30-day follow-up. Within 90 days postprocedure, the mortality rate was 3.1%. No tearing or psuedoaneurysm of the apex was observed. No myocardial infarctions were observed and apical myocardial function was preserved. Considering the STASIS data, the probability of any adverse event related to the device are extremely low. Any harmful events requiring additional therapy would be expected to be observed within the 90-day STASIS study. There were no additional patient risks associated with the Permaseal over the standard of care, including the risks of bleeding, aneurysm, or pseudoaneurysm.
The probable benefits of the device are also based on nonclinical laboratory, animal studies as well as data collected in a clinical study as described above. The Permaseal provides a minimally invasive reproducible technique for apical closure that distributes tension equally and circumferentially around a trans-apical access point. Apical device closure, defined as freedom from pulsatile bleeding requiring significant surgical intervention (more than one pledgeted suture), was achieved in 93.5% of patients. No patients required re-operation for bleeding at the apical access site and results were durable through 90 days. There was also no death or stroke observed in the 30-day follow-up interval of the STASIS trial.
Additional factors to be considered in determining the probable risks and benefits for the Permaseal include that the placement of the Permaseal device is at least as safe and effective as the current standard of care. The additional probable benefits of the Permaseal device include reduction of apical bleeding complications, the minimization of apical myocardial injury that might result in apical akinesis or dyskinesis, reduction in procedural time, and reduction in procedural bleeding related to apical leak. Furthermore, patients would likely value a secure and less traumatic procedure available with the use of the Permaseal device. It is also important to note that the standard of care, which is closure using manually placed purse-strings or mattress sutures during surgery, is not precluded by the Permaseal if failure were to occur. Finally, the Permaseal is placed epicardially as a cinching mechanism and no device components remain in contact with the bloodstream or intra-ventricular cavity.
13
Patient Perspectives
This submission did not include specific information on patient perspectives for this device.
Benefit/Risk Conclusion
In conclusion, given the available information above, the data supports that for soft tissue approximation of cardiac apical tissue during transcatheter valve replacement, the probable benefits outweigh the probable risks for the Permaseal device. The device provides substantial benefits and the risks can be mitigated by the use of general and the identified special controls.
CONCLUSION
The de novo request for the Permaseal is granted and the device is classified under the following:
Product Code: PNQ Device Type: Apical Closure Device Class: II Regulation: 21 CFR 870.4510