LIQUIFIX FIX8 Hernia Mesh Fixation (HMF) Device, LIQUIFIX Precision Open Hernia Mesh Fixation Device

P220024 · Advanced Medical Solutions Limited · PLJ · Jun 2, 2023 · General, Plastic Surgery

Device Facts

Record IDP220024
Device NameLIQUIFIX FIX8 Hernia Mesh Fixation (HMF) Device, LIQUIFIX Precision Open Hernia Mesh Fixation Device
ApplicantAdvanced Medical Solutions Limited
Product CodePLJ · General, Plastic Surgery
Decision DateJun 2, 2023
DecisionAPPR
Regulation21 CFR 878.4010
Device ClassClass 3
AttributesTherapeutic

Intended Use

LIQUIFIX FIX8™ The LIQUIFIX FIX8™ Hernia Mesh Fixation device is intended for use in laparoscopic surgical repair of groin (inguinal and femoral) hernias, achieved through the fixation of prosthetic polypropylene or polyester mesh to the abdominal wall and the approximation of the peritoneum. LIQUIFIX Precision™ Open The LIQUIFIX Precision™ Open Hernia Mesh Fixation device is intended for use in open surgical repair of groin (inguinal and femoral) hernias, achieved through the fixation of prosthetic polypropylene or polyester mesh to the abdominal wall.

Device Story

Device uses n-butyl-2-cyanoacrylate adhesive to fix hernia mesh to tissue and approximate peritoneum. Consists of liquid adhesive in glass vial and delivery instrument (cannula, handle, trigger). Operated by surgeons in OR. Trigger pull dispenses adhesive drop; polymerizes on contact with moisture/tissue. Replaces mechanical fasteners (tacks/sutures/staples) to reduce nerve entrapment/irritation. Atraumatic fixation benefits patient by potentially reducing chronic pain. Used in laparoscopic (FIX8) and open (Precision) groin hernia repairs.

Clinical Evidence

Pivotal IDE study (LBF8-01) randomized 284 patients (142 LiquiFix, 142 control) to evaluate non-inferiority in pain reduction (VAS) at 6 months. Primary endpoint met (p<0.025). Secondary endpoints (hernia recurrence, mesh fixation, peritoneal closure) met non-inferiority criteria. Safety profile comparable to control; no device-related deaths. OUS studies (n=504) and registry data (n=141) support safety/effectiveness. Bench and animal studies confirmed tensile strength and biocompatibility.

Technological Characteristics

Consists of n-butyl-2-cyanoacrylate monomer in sealed glass vial and sterile, single-use delivery instrument (cannula, handle, trigger). Adhesive is non-bioabsorbable. Sterilized via e-beam and ethylene oxide. Meets ISO 10993-1 biocompatibility requirements. ASTM F2255 (lap shear) and ASTM 2256 (T-peel) used for performance testing.

Indications for Use

Indicated for laparoscopic or open surgical repair of groin (inguinal and femoral) hernias in patients ≥22 years old, involving fixation of polypropylene or polyester mesh to the abdominal wall and peritoneal approximation (laparoscopic only). Contraindicated in patients with hypersensitivity to cyanoacrylate, formaldehyde, or D&C Violet No. 2; use on PTFE mesh; or closure of cerebral tissues, blood vessels, or peripheral nerves.

Regulatory Classification

Identification

A tissue adhesive for the topical approximation of skin is a device intended for topical closure of surgical incisions, including laparoscopic incisions, and simple traumatic lacerations that have easily approximated skin edges. Tissue adhesives for the topical approximation of skin may be used in conjunction with, but not in place of, deep dermal stitches.

Special Controls

*Classification.* Class II (special controls). The special control for this device is FDA's “Class II Special Controls Guidance Document: “Tissue Adhesive for the Topical Approximation of Skin.” See § 878.1(e) of this chapter for the availability of this guidance document.(b) *Tissue adhesive for non-topical use* —(1)*Identification.* A tissue adhesive for non-topical use, including adhesives intended for use in the embolization of brain arteriovenous malformation or for use in ophthalmic surgery, is a device used for adhesion of internal tissues and vessels.(2) *Classification.* Class III (premarket approval). As of May 28, 1976, an approval under section 515 of the act is required before this device may be commercially distributed. See § 878.3 of this chapter.

Predicate Devices

Related Devices

Submission Summary (Full Text)

{0} SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) I. GENERAL INFORMATION Device Generic Name: Hernia Mesh Fixation Device Device Trade Name: LiquiFix FIX8™ Hernia Mesh Fixation device. LiquiFix Precision™ Open Hernia Mesh Fixation device. Device Procode: PLJ Applicant’s Name and Address: Advanced Medical Solutions Limited, Western Wood Way, Langage Science Park, Plymouth, Devon, UK, PL7 5BG Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P220024 Date of FDA Notice of Approval: June 2, 2023 II. INDICATIONS FOR USE LIQUIFIX FIX8™ The LIQUIFIX FIX8™ Hernia Mesh Fixation device is intended for use in laparoscopic surgical repair of groin (inguinal and femoral) hernias, achieved through the fixation of prosthetic polypropylene or polyester mesh to the abdominal wall and the approximation of the peritoneum. LIQUIFIX Precision™ Open The LIQUIFIX Precision™ Open Hernia Mesh Fixation device is intended for use in open surgical repair of groin (inguinal and femoral) hernias, achieved through the fixation of prosthetic polypropylene or polyester mesh to the abdominal wall. III. CONTRAINDICATIONS - The device is not intended for use when prosthetic material fixation is contraindicated. - Do not use on patients with a hypersensitivity to cyanoacrylate adhesives, formaldehyde, or D&amp;C Violet No. 2 dye - Do not use for the fixation of meshes constructed with polytetrafluoroethylene (PTFE). or materials other than polypropylene or polyester. - Do not use device for closure or fixation of cerebral tissues, blood vessels or peripheral nerves. Doc ID 04379.02.02 Downloaded and/or hard copy uncontrolled. Controlled version in CDRH Docs. 1 of 55 {1} Doc ID 04379.02.02 Downloaded and/or hard copy uncontrolled. Controlled version in CDRH Docs. 2 of 55 # IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the LIQUIFIX labeling. Specific warning for use of LiquiFix in anchoring mesh in open inguinal hernia repair will restrict its use of application directly on the mesh positioned as an onlay on the floor of the inguinal canal, as in a Lichtenstein repair or with use of mesh to reinforce a primary repair. # V. DEVICE DESCRIPTION The LIQUIFIX FIX8™ and LIQUIFIX Precision™ Open Hernia Mesh Fixation devices are designed for the application of an n-butyl-2- cyanoacrylate adhesive to an implanted hernia repair mesh, in order to affix the mesh to the underlying tissue. Additionally, the device may be used for tissue-to-tissue approximation of the peritoneum (LIQUIFIX FIX8™ Laparoscopic Hernia Mesh Fixation device). The adhesive is non- bioabsorbable and becomes encapsulated within the body, along with the hernia mesh. A representative image of the hernia mesh fixation devices is provided in Figure 1-2. ![img-0.jpeg](img-0.jpeg) Figure 1: LIQUIFIX FIX8™ Laparo Hernia Mesh Fixation device ![img-1.jpeg](img-1.jpeg) Figure 2: LIQUIFIX Precision™ Open Hernia Mesh Fixation device {2} Device Composition/Key Components/Materials The LIQUIFIX Hernia Mesh Fixation devices consist of: - n-butyl-2-cyanoacrylate adhesive monomer (cyanoacrylate adhesive), in liquid form, supplied in a thin-walled, sealed glass vial; and - a surgically invasive, delivery instrument comprising a cannula, with a handle at the proximal end incorporating a loading chamber, filter, piston chamber and trigger. The distal tip of the device is open to allow the adhesive to be dispensed from it. Both the cyanoacrylate adhesive in the glass vial and the surgically invasive delivery device are supplied sterile, for single use only. The device releases a drop of adhesive (anchor) when the trigger is pulled and released, which polymerizes on contact with tissue or moisture. VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several alternative practices for the correction of groin (inguinal and femoral) hernia, which can be divided into non-surgical and surgical treatment. Usually if the hernia has no symptoms, a conservative non-surgical approach and watchful waiting may be an option. Conservative treatment of hernias includes the use of a corset, truss, or a belt, which applies pressure at the site. Surgical options include tissue approximation repairs (non-mesh repairs) with sutures at the site of the weakness or defect. In addition, a tension-free hernia repair using hernia mesh may be performed either laparoscopically or via open hernia repair using conventional mechanical fasteners such as metallic or absorbable tacks, sutures or staples. Adhesives, either synthetic adhesives such as cyanoacrylate, or biological products such as fibrin glue, have been introduced as an option for mesh fixation since this approach eliminates direct nerve irritation and nerve entrapment due to their atraumatic nature. Alternatively, absorbable microhooks on the fascia-facing side of mesh which induce a “self-gripping” property, negates any additional type of fixation. For closure of the peritoneum during laparoscopic TAPP hernia repair, the peritoneum may be closed with several traditional closure techniques including sutures, tacks, and staples. Following closure of the peritoneum, standard practices and procedures are used for the subsequent closure of the fascial defect and skin. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle. VII. MARKETING HISTORY The LIQUIFIX FIX8™ Laparoscopic Hernia Mesh Fixation device has been commercially available outside the United States (under brand name LiquiBand FIX8® Laparo) since 2014 Doc ID 04379.02.02 Downloaded and/or hard copy uncontrolled. Controlled version in CDRH Docs. 3 of 55 {3} for use in the laparoscopic surgical repair of inguinal and ventral incisional hernias, achieved through the fixation of prosthetic mesh to the abdominal wall and the approximation of the peritoneum. The product is currently distributed globally including regions such as Europe, Latin America, North America (Canada), Asia and Pacific and Middle East, as detailed in Table 1 below. Table 1: Countries where the CE-marked version of Laparoscopic Hernia Mesh Fixation device has been marketed | Argentina | Israel | Singapore | | --- | --- | --- | | Armenia | Malaysia | Taiwan | | Australia | Mexico | Ukraine | | Canada | New Zealand | United Arab Emirates | | Costa Rica | Peru | United Kingdom | | Ecuador | Saudi Arabia | Philippines | | EU | Serbia | Sri Lanka | | India | | Republic of Korea | The LIQUIFIX Precision™ Open Hernia Mesh Fixation device has been commercially available outside the United States since 2018. The product is currently distributed globally including regions such as Europe, Latin America, North America (Canada), Asia and Pacific and Middle East. There has been one Outside US voluntary recall for the LiquiBand FIX8® Open device in January 2022 due to a mechanical device defect observed during internal testing of the device, and the device was modified to improve the seal tolerance, and verification completed. The recall has been closed and device made available. Table 2: Countries where the CE-marked version of Open Hernia Mesh Fixation device has been marketed | Australia | India | Philippines | | --- | --- | --- | | Brazil | Israel | Malaysia | | Canada | New Zealand | Singapore | | Ecuador | Saudi Arabia | Mexico | | EU | Ukraine | United Kingdom | # VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of the potential adverse effects (e.g., complications) associated with the use of LIQUIFIX FIX8™ and LIQUIFIX Precision™ Open. The adverse events associated with the device are similar to those of traditional surgical hernia repair procedures. As with the majority of implanted devices, adverse reactions associated with the use of this device may include transient local irritation at the implant site and a transitory inflammatory foreign body response. Advanced Medical Solutions has determined the potential adverse effects Doc ID 04379.02.02 Downloaded and/or hard copy uncontrolled. Controlled version in CDRH Docs. {4} (e.g., complications) listed below may be associated with the use of the LIQUIFIX devices. These potential adverse events include, but are not limited to, the following: - Toxic reaction - Allergic reaction Clinical studies of LIQUIFIX adhesive using the Laparoscopic model of the device have been conducted inside and outside the United States. Adverse events observed during the US pivotal study have been described below; a number of these adverse events were possibly device related and possibly/definitely related to the procedure. In addition, adverse events observed during the four LiquiBand FIX8® (identical to LIQUIFIX FIX8™ except labelling) inguinal/femoral hernia repair European clinical studies, but not necessarily related to the device itself, included the following: - Chronic Pain - Hernia Recurrence - Seroma - Hematoma - Swelling - Neuralgia / Hypoesthesia - Groin/ Testicular pain - Intestinal obstruction - Genital hemorrhage - Spermatic Cord Inflammation - Orchitis - Lymphadenitis - Mesh infection - Urinary Retention - Minor Surgical Emphysema - Port Site Hernia - Port Site Hemorrhage - Inadvertent enterotomy - Intra peritoneal bleeding - Post-operative ileus - Urinary bladder injury Due to the identical adhesive, the adverse events are considered applicable to the LIQUIFIX Precision™ Open Hernia Mesh Fixation device as well. For the specific adverse events that occurred in the clinical studies, please see Section X Summary of Primary Clinical Study below. IX. SUMMARY OF NONCLINICAL STUDIES A variety of non-clinical testing was performed with the LIQUIFIX FIX8™ device and the LIQUIFIX Precision™ Open device. Doc ID 04379.02.02 Downloaded and/or hard copy uncontrolled. Controlled version in CDRH Docs. 5 of 55 {5} A summary of testing has been provided in Table 3 below. # A. Laboratory Studies A brief summary of adhesive key performance specifications for both LIQUIFIX FIX8™ and LIQUIFIX Precision™ Open conducted via bench top studies has been provided below. Device testing for LIQUIFIX FIX8™ and LIQUIFIX Precision™ Open has been performed and passed. Table 3: Laboratory Studies - LIQUIFIX adhesive | Test | Purpose | | --- | --- | | Material Characterization | | | Set Time | This test evaluates: • Set time for adhesive polymerization (pre-sterile, post-sterile and aged adhesive) on salt solution. • Set time for mesh fixation. • Set time under different environmental conditions (saturated and dry conditions). | | Tensile Strength – Lap Shear (mesh-to-tissue) | This test evaluates lap shear strength (ASTM F2255) of adhesive with hernia meshes. | | Tensile Strength – T Peel | This test evaluates T-peel tensile strength (ASTM 2256) of adhesive attachment of mesh to tissue. | | Viscosity | This test evaluates viscosity (cP) of the adhesive in comparison to other marketed cyanoacrylates. | | Heat Polymerization | This test evaluates the heat of polymerization of adhesive on porcine tissue. | | LIQUIFIX Applicator Testing | | | Crush Force (LIQUIFIX FIX8™ model) | This test evaluates crush force of the crush cover of the device (required during priming) using a tensile test machine. | | Torsional Loading (tip rotation) (LIQUIFIX FIX8™ model) | This test evaluates torsional loading of the shaft of the device using a torque meter until failure. | | Tip Loading (tip deflection) (LIQUIFIX FIX8™ model) | This test evaluates tip deflection of the device after 50mm deflection. | | Anchor size | This test evaluates average weight of the adhesive anchor (drop) after expression from the applicator device. | | Dispense rate(LIQUIFIX FIX8™ model) | This test evaluates the average time taken to deploy a single adhesive anchor (following ten adhesive drops). | | Dispense Angle (LIQUIFIX FIX8™ model) | This test evaluates the ability of the applicator to dispense adhesive at the clinically relevant angles. | Doc ID 04379.02.02 Downloaded and/or hard copy uncontrolled. Controlled version in CDRH Docs. {6} | Back pressure(LIQUIFIX FIX8™ model) | This test evaluates the performance of the device under pressure (within a pressurized vessel). | | --- | --- | | Insertion (LIQUIFIX FIX8™ model) | This test evaluates any drop in pressure. | | Performance time | This test evaluates the ability of the device to dispense adhesive after 3±0.5 hours. | | Anchor quantity | This test evaluates the total number of drops (adhesive anchor) a device can deliver. | | Device | This test evaluates the device through visual inspection. | | Device Leak (LIQUIFIX Precision™ model) | This test evaluates device leak when at rest in all orientations. | | Adhesive gauge (LIQUIFIX Precision™ model) | This test evaluates gauge movement with every adhesive anchor delivered. | | Ability to crack glass ampoule (LIQUIFIX Precision™ model) | This test evaluates the ability of the user to turn the ampoule plunger clockwise to break glass ampoule. | ## B. Animal Studies Pre-clinical testing was performed in porcine and rabbit models to evaluate the safety and effectiveness of the LIQUIFIX adhesive and LIQUIFIX FIX8™ device (Table 4). The definitive animal studies support that the LIQUIFIX adhesive performs as intended. Table 4: Results of unpublished animal studies | Test | Purpose | | | --- | --- | --- | | Pilot Study: Porcine evaluation of the feasibility of the LIQUIFIX FIX8™ device for the surgical repair of hernia mesh and the closure of the peritoneum. | Early feasibility study to assess the performance of LIQUIFIX FIX8™ in vivo in three Swine. | The LIQUIFIX adhesive was found to provide fixation of adequate tensile strength to fix mesh within the pilot porcine study. No apparent mesh migration was observed at the day 14 time-point. Macroscopic and histological analysis 2 weeks post- fixation revealed a significant level of fibrosis and integration of the mesh into surrounding tissues. No adverse irritation or inflammation of the graft site was observed beyond what is typically expected following implantation of a foreign body. | Doc ID 04379.02.02 Downloaded and/or hard copy uncontrolled. Controlled version in CDRH Docs. 7 of 55 {7} | Definitive study: Evaluation of LIQUIFIX FIX8™ in an Abdominal Wall Incision Model in Swine, 2 and 4 weeks. | Definitive study to evaluate the local effects and adhesion formation of LIQUIFIX FIX8™ when applied to abdominal wall incisions of the peritoneum in swine. Incisions in the peritoneum of the ventro-lateral abdominal wall were closed with either LIQUIFIX FIX8™ or polypropylene suture. | Under the conditions of this study, LIQUIFIX FIX8™ was considered to elicit a slight reaction in the tissue as compared to the control article (polypropylene suture), at 2- and 4- weeks following closure of the peritoneum of the pig. The sites were macroscopically normal. The additional evaluation of the left iliac vein and genital branch of the genitofemoral nerve, when exposed to the test article, resulted in no microscopic evidence of tissue injury at the sites when polymerized article was peeled away from nerve and vein tissue of freshly euthanized animals. | | --- | --- | --- | | Definitive study: Evaluation of LIQUIFIX FIX8™ Laparoscopic in a Rabbit Abdominal Wall Defect Model - 2, 4, and 13 Weeks | An abdominal midline ventral incision was created to adequately expose the peritoneal surface of the abdominal wall in New Zealand White rabbits. LIQUIFIX FIX8™, and comparative control article, non-absorbable suture, were then used to fix the hernia mesh to the abdominal wall. | Under the conditions of this study, LIQUIFIX FIX8™ was considered to elicit minimal or no reaction in the tissue as compared to the comparative control article (polypropylene suture) when implanted in the abdominal wall of rabbits for 2, 4 and 13 weeks. | ## C. Additional Studies ### 1. Biocompatibility Biocompatibility testing of the LIQUIFIX adhesive in its polymerized form and over the course of its polymerization reaction was performed. The applicator device materials which contact the patient or the adhesive pathway were also assessed for each device (LIQUIFIX FIX8™ and LIQUIFIX Precision™ Open). Table 5 briefly summarizes the testing performed on LIQUIFIX adhesive. In addition, chemical characterization of the adhesive was performed. The tests demonstrated appropriate biocompatibility, chemical characterization, and physical/chemical characterization. Doc ID 04379.02.02 Downloaded and/or hard copy uncontrolled. Controlled version in CDRH Docs. 8 of 55 {8} Table 5: Results of Biocompatibility Testing – LIQUIFIX adhesive (pre-polymerized, in situ polymerizing and polymerized state) | Biological Endpoint | Study Type | | --- | --- | | Cytotoxicity | Cytotoxicity MTT ISO 10993-5 | | Sensitization | Kligman Maximization ISO 10993-10 | | Irritation | Intracutaneous Injection ISO 10993-10 | | Acute Toxicity | Acute Systemic Injection ISO 10993-11 | | Systemic Toxicity | Systemic Toxicity by subcutaneous Implantation – 28 days ISO 10993-11 | | Systemic Toxicity | Systemic Toxicity by subcutaneous Implantation – 90 days ISO 10993-11 | | Genotoxicity | Reverse Mutation Assay ISO 10993-3 | | Genotoxicity | Mouse Lymphoma Mutagenesis Assay ISO 10993-3 | | Genotoxicity | Rodent Blood Micronucleus Assay ISO 10993-3 | | Implantation effects | Intramuscular Implantation – 4 weeks ISO 10993-6 | | Implantation effects | Intramuscular Implantation – 13 weeks ISO 10993-6 | | Material Mediated Pyrogen | Material Mediated Pyrogen ISO 10993-11 | | Chemical Characterization: Interaction between adhesive and mesh. Polymerization of adhesive. Potential hydrolytic degradation. | Chemical Characterization ISO 10993-12 ISO 10993-18 | | Physical/ chemical characterization | EN 14477 | Doc ID 04379.02.02 Downloaded and/or hard copy uncontrolled. Controlled version in CDRH Docs. 9 of 55 {9} The following testing was performed on the LIQUIFIX FIX8™ and LIQUIFIX Precision™ Open device applicator components which make direct/indirect contact with the patient: - Cytotoxicity (Cytotoxicity Elution Method ISO 10993-5 / Cytotoxicity MTS) - Irritation (Intracutaneous Injection ISO 10993-10) - Sensitization (Kligman Maximization ISO 10993-10) - Extraction Study (Chemical Characterization EN ISO 10993-12, EN ISO 10993-18) The LIQUIFIX Hernia Mesh Fixation devices are considered to meet the requirements of ISO 10993-1 for its intended use, and so can be considered biologically safe. ## 2. Sterilization The LIQUIFIX FIX8™ and LIQUIFIX Precision™ Open Hernia Mesh Fixation devices are supplied sterile. The devices are sterilized using both electron beam (e-beam) irradiation and ethylene oxide (EO) to a sterility assurance level (SAL) of 10-6. ## 3. Packaging Validation The results of the ISTA 3a transit testing performed with final packaged LIQUIFIX FIX8™ and LIQUIFIX Precision™ Open devices deemed that the device was successfully validated in the transit study. ## 4. Shelf-Life Validation At interim and end of shelf life timepoints, product was evaluated for conformance with functional performance specification and adhesive specification. Conformance with the tested specifications was confirmed at the end of shelf life. Real time stability data available at the time of PMA approval establishes a shelf life of 18 months for LIQUIFIX Hernia Mesh Fixation Devices. ## X. SUMMARY OF PRIMARY CLINICAL STUDY(IES) The clinical evidence supporting the safety and effectiveness of the LIQUIFIX FIX8™ and LIQUIFIX Precision™ Open devices is derived from a combination of a US clinical IDE study and Outside-US clinical studies and post market surveillance (real world evidence). The Applicant performed a clinical study under the IDE pathway to establish a reasonable assurance of safety and effectiveness of the surgical repair of groin (inguinal and femoral) hernias, achieved through the fixation of prosthetic mesh to the abdominal wall and the approximation of peritoneum in the US under IDE G190018. Data from this clinical study were the basis for the PMA decision, as well as additional foreign (OUS) clinical data supporting the US clinical data. PMA P220024: FDA Summary of Safety and Effectiveness Data 10 of 55 {10} # Pivotal Clinical Study (LBF8-01 Clinical Evaluation of LIQUIFIX FIX8™) ## A. Study Design The safety and effectiveness of LIQUIFIX FIX8™ is derived from one US pivotal study and several clinical studies performed outside-US. The US pivotal study has been summarized below. A prospective randomized, controlled, single blinded, parallel-group, IDE non-inferiority study was conducted to evaluate the clinical performance and safety of LIQUIFIX FIX8™ versus control (absorbable tacker) for hernia mesh fixation and peritoneal closure in groin (inguinal and femoral) hernia repair. Two hundred and eighty-four (284) patients from five (5) investigational sites across the USA were enrolled in the study. 186 patients underwent Transabdominal preperitoneal repairs (TAPP) and 98 patients underwent Totally Extraperitoneal repairs (TEP) equally divided into the two experimental groups for each surgical approach. The primary endpoint of improvement in pain is evaluated at the 6-month visit and measures the reduction of recorded Visual Analog Scale (VAS) since baseline (worst pain experienced within 1 month of screening visit). Following discharge, study subjects entered the follow-up period consisting of in-clinic and remote visits to assess primary endpoint of improvement in pain not inferior to control device as measured by a VAS value (0 = no pain to 10 = most pain imaginable) from baseline (worst pain experienced within 1 month of screening visit) to six months post hernia repair. The secondary endpoints of mesh fixation and peritoneal closure (Trans abdominal preperitoneal (TAPP) repairs only) were assessed at time of surgery. Following discharge, study subjects entered the follow-up period consisting of in-clinic and remote visits to assess the secondary endpoints of pain experienced, quality of life as well as the incidence of hernia recurrence and adverse events. Follow-up visits were performed at discharge and then post-operatively at week 1, week 2, month 1, month 3, month 6, month 9 and month 12. ## The secondary endpoints were: - To evaluate the incidence of hernia recurrence in patients following laparoscopic (Totally Extraperitoneal (TEP) and TAPP) hernia repair using LIQUIFIX FIX8™ or control device. - To compare the use of LIQUIFIX FIX8™ to control device for mesh fixation at time of surgery. - To compare the use of LIQUIFIX FIX8™ to control devices for the approximation of the peritoneum (TAPP repairs only) at time of surgery. - To evaluate the quality of life experienced by subjects following groin hernia repair by LIQUIFIX FIX8™ or control as measured by the Carolinas Comfort Scale (CCS) at baseline (prior to surgery), and at 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, and 12 months following surgery. - To compare levels of pain experienced following laparoscopic (TEP and TAPP) groin hernia repair by LIQUIFIX FIX8™ or control device, as measured by VAS at discharge, and at 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, and 12 months following surgery. PMA P220024: FDA Summary of Safety and Effectiveness Data {11} - To evaluate the safety of LIQUIFIX FIX8™ and control device for groin hernia repair by comparing incidence of adverse events in patients post laparoscopic groin hernia repair. The control group is an FDA-cleared tacker device with similar indications for use, AbsorbaTack™ 5mm Absorbable Fixation Device (Medtronic/Covidien). AbsorbaTack™ is intended for fixation of prosthetic material to soft tissue in various minimally invasive and open surgical procedures such as hernia repair. A total of 284 patients had their surgical procedure performed between August 22, 2019 and December 03, 2021 (LIQUIFIX FIX8™ n=142; AbsorbaTack™ n=142). The data for this PMA reflected complete data collected through to January 23, 2023. At 6-month follow-up, out of 284 randomized patients, 282 were eligible (Eligible: Last Follow-up date &gt; Visit 6 Window Open date), clinical follow-up was performed in 269 patients (136 LIQUIFIX FIX8™, 133 AbsorbaTack™). At 6-month follow-up, seven patients (5 LIQUIFIX FIX8™, 2 AbsorbaTack™) were lost-to-follow-up with their last visit occurring prior to Month 6, and six patients (1 LIQUIFIX FIX8™, 5 AbsorbaTack™) missed the 6-month visit, but had completed the study. The other 2 patients were ineligible; one patient (control) was lost to follow up and one patient (control) withdrew consent. At 12-month follow-up, out of 284 randomized patients, 276 were eligible (Eligible: Last Follow-up date &gt; Visit 12 Window Open date), 266 patients completed clinical follow-up (132 LIQUIFIX FIX8™; 134 AbsorbaTack™). At 12 month follow-up, 10 patients (6 LIQUIFIX FIX8™, 4 AbsorbaTack™) were lost to follow-up. 1 patient experienced an SAE that prevented attending all study visits and was deemed not eligible for 12 month visit because their study exit date was prior to the Month 12 Visit Window opening. Note, their study exit was assigned to the 12-month column because their study exit date was after the Month 9 visit closed. The other 7 patients were ineligible; six patients (2 LIQUIFIX FIX8™, 4 AbsorbaTack™) were lost to follow up and one patient (AbsorbaTack™) withdrew consent. 1. Clinical Inclusion and Exclusion Criteria Enrollment in the LBF8-01 study was limited to patients who met the following inclusion criteria: 1) Is male or female, ≥22 years of age. 2) Is willing and able to give written informed consent. 3) Has a primary or recurrent groin hernia (unilateral or bilateral, inguinal or femoral). 4) Is currently scheduled and eligible for TAPP or TEP laparoscopic groin hernia repair (inguinal or femoral). 5) Hernia mesh to be used at the time of surgery is at least 4” x 6” in size and is one of the following: a. 3D Max™ Mesh (Bard Inc.) b. 3D Max™ Light (Bard Inc.) PMA P220024: FDA Summary of Safety and Effectiveness Data 12 of 55 {12} c. Parietex™ 2D (order code starting with TEC) Flat Sheet Mesh (Medtronic) d. Parietex™ 3D (order code starting with TET) Flat Sheet Mesh (Medtronic) 6) Is willing and able to comply with the protocol assessments at time of surgery and during the post-surgical follow up period. Patients were not permitted to enroll in the LBF8-01 study if they met any of the following exclusion criteria: 1) Has a hernia type not suitable for laparoscopic hernia repair as determined by the Investigator (i.e., strangulated). 2) Subject has a recurrent groin hernia previously repaired laparoscopically, has an anatomical defect or had prior surgical procedures that in the opinion of the Investigator prevents access to the pre-peritoneal space for TAPP or TEP laparoscopic hernia repair 3) Is pregnant or actively breastfeeding. 4) Has a known sensitivity to cyanoacrylate or formaldehyde, D&amp;C Violet No.2 dye or any component of LIQUIFIX FIX8™ or control device. 5) Has an active or potential infection at the surgical site or systemic sepsis. 6) Hernia mesh to be used at surgery is less than 4"x6" in size, or not one of the types of mesh listed in Inclusion Criteria #5. 7) Cannot tolerate general anesthesia. 8) Has any significant or unstable medical or psychiatric condition that, in the opinion of the Investigator, would interfere with his/her ability to participate in the study. 9) Is currently enrolled in another clinical study or undergoing treatment with another investigational drug or device. ## 2. Follow-up Schedule All patients were scheduled to return for follow-up assessments post-surgery at Day 7 (±3 days); Day 14 (-3/+6 days); Month 1 (±7 days); Month 3 (±14 days); Month 6 (-21/+14 days); Month 9 (-21/+14 days); and Month 12 (-21/+14 days). Preoperatively, the patient's medical history, demographic data, current analgesic usage, and hernia information was collected. Vital signs, subject pain (VAS) and Quality of Life assessment was also performed. All pre-surgical and surgical procedures up until mesh fixation and peritoneal closure (TAPP repairs only), were performed as per investigational site standard of care. On the day of surgery, analgesic usage and vital signs were recorded. A pregnancy test was performed on women of child-bearing potential prior to surgery. Randomization to either Investigational or control device occurred at the surgery visit (Visit 2) and therefore the subjects were blinded to their randomly assigned treatment device prior to surgery and during the follow up period following surgery. Intraoperatively, hernia information (type and size) was confirmed as well as the use of investigational or control device and any inadvertent application, photograph of mesh fixation and peritoneal closure (where applicable) and an evaluation of any adverse events observed. PMA P220024: FDA Summary of Safety and Effectiveness Data 13 of 55 {13} At discharge, pain medications, other pain management therapies and vital signs were recorded as well as any complications or adverse events. A pain (VAS) assessment of the hernia repair was also captured on discharge. Throughout follow-up, any suspected hernia recurrence was confirmed by ultrasound imaging. Postoperatively, the objective parameters measured during the study included: - Analgesic usage or other pain management therapies at all post-operative follow-up visits. - Vital signs (Day 14, Month 3, and Month 6). - Clinician evaluation of hernia repair (Day 14 in-clinic visit, Month 3, and Month 6). - Subject pain (Visual Analog Scale) assessment using VAS pain assessment tool at all post-operative follow-up visits. - Subject Quality of Life (Carolina Comfort Scale) questionnaire at all post-operative follow-up visits. - Adverse Event evaluation at all post-operative follow-up visits. The schedule of assessments is summarized in Table 6 below. PMA P220024: FDA Summary of Safety and Effectiveness Data 14 of 55 {14} Table 6: Schedule of assessments | | Pre-Surgery | Surgery | Discharge | Post-Surgery Visits | | | | | | | Unscheduled visit | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Visit | 1 | 2 | 3^{1} | 4 | 5 | 6 | 7 | 8 | 9 | 10 | N/A | | Day / Month | ≤21 Days | Day 0 | Day 0 or 1 | Day 7 | Day 14 | Month 1 | Month 3 | Month 6 | Month 9 | Month 12 | N/A | | Visit Window (Days) | | | | ±3 | -3 / +6 | ±7 | ±14 | -21 / +14 | -21 / +14 | -21 / +14 | N/A | | Informed Consent | X | | | | | | | | | | | | Inclusion/Exclusion | X | | | | | | | | | | | | Pregnancy Test (if applicable) | | X^{1} | | | | | | | | | | | Medical History | X | | | | | | | | | | | | Analgesics usage | X | X^{1} | X | X | X | X | X | X | X | X | X | | Demographics | X | | | | | | | | | | | | Vital Signs (HR/BP/T/Ht/Wt)^{4} | X | X^{1} | X | | X | | X | X | | | X | | Randomization^{5} | | X^{2} | | | | | | | | | | | Hernia Information (type & size) | X | X^{2} | | | | | | | | | | | Use of Investigational or control device | | X^{2} | | | | | | | | | | | Number of Investigational or control device applications | | X^{2} | | | | | | | | | | | Photograph following mesh fixation | | X | | | | | | | | | | | Photograph following peritoneal closure^{6} | | X | | | | | | | | | | | Clinician evaluation of hernia repair & PE^{7} | | | | | X | | X | X | | | X | | Subject Pain (0-10 VAS) Assessment | X | | X | X | X | X | X | X | X | X | | | Subject QOL Assessment | X | | | X | X | X | X | X | X | X | | | AE Evaluation | | X^{2} | X | X | X | X | X | X | X | X | X | | 1Immediately prior to surgery 2During surgery 3At discharge post-surgery, either on same day as surgery or next day post-surgery according to standard of care. 4Height only required at Pre-surgery visit. Unless Pre-surgery (Visit 1), Surgery (Visit 2) and Discharge (Visit 3) occur on the same date, weight should be obtained for each separate visit. Vital signs may be obtained remotely at Month 3 and 6 visits as volunteered by subjects using their own devices as available (e.g. thermometer, weight scales, smart wearable technology). 5Patient must be blinded to the randomization device 6Photograph following peritoneal closure only required for TAPP repairs. 7Suspected hernia recurrence will be confirmed by ultrasound imaging following physical examination. HR: Heart rate; BP: Blood pressure; T: Temperature; Ht: Height; Wt: Weight; PE: Physical Examination; VAS: Visual Analog Scale; QOL: Quality of Life; AE: Adverse Event. Shaded columns are in-clinic visits. | | | | | | | | | | | | PMA P220024: FDA Summary of Safety and Effectiveness Data {15} PMA P220024: FDA Summary of Safety and Effectiveness Data 16 of 55 # 3. Clinical Endpoints With regards to success/failure criteria, the study was designed with a non-inferiority hypothesis for the primary effectiveness endpoint of pain at 6 months. Success was determined by improvement in pain not inferior to control device as measured by a VAS value (0 = no pain to 10 = most pain imaginable) from baseline (worst pain experienced within 1 month of screening visit) to six months post hernia repair. The primary effectiveness endpoint was tested for non-inferiority of treatment to control with a predefined non-inferiority margin of 0.9 on the VAS scale. The primary effectiveness endpoint was assessed with the following hypothesis: $$ \mathrm{H}_0: \delta_{\mathrm{T}} - \delta_{\mathrm{C}} \geq 0.9 $$ $$ \mathrm{H}_a: \delta_{\mathrm{T}} - \delta_{\mathrm{C}} &lt; 0.9 $$ where $\delta$ is the change from baseline worst pain experienced within 1 month of screening visit) to 6-month on VAS for the appropriate treatment group. With regard to effectiveness, there are six secondary endpoints in the clinical study, three of which have associated hypothesis tests. - Recurrence rate in subjects following laparoscopic (TEP and TAPP) groin hernia repair by LIQUIFIX FIX8™ or control (AbsorbaTack™) at 6 months. $$ \mathrm{H}_0: q_{\mathrm{T}} - q_{\mathrm{C}} \geq 10\% $$ $$ \mathrm{H}_1: q_{\mathrm{T}} - q_{\mathrm{C}} &lt; 10\%, $$ where $q$ is the recurrence rate at 6 months for the appropriate treatment group. - Rate of successful hernia mesh fixation in subjects undergoing TEP and TAPP laparoscopic groin hernia repair. $$ \mathrm{H}_0: p_{\mathrm{C}} - p_{\mathrm{T}} \geq 10\% $$ $$ \mathrm{H}_1: p_{\mathrm{C}} - p_{\mathrm{T}} &lt; 10\%, $$ where $p$ is the rate of successful hernia mesh fixation at time of surgery for the appropriate treatment group. Unsuccessful mesh fixation is defined as requiring the use of an alternative fixation device or additional procedure to achieve adequate fixation at time of surgery. - Rate of successful peritoneal closure in subjects undergoing laparoscopic TAPP hernia repair. $$ \mathrm{H}_0: \pi_{\mathrm{C}} - \pi_{\mathrm{T}} \geq 15\% $$ $$ \mathrm{H}_1: \pi_{\mathrm{C}} - \pi_{\mathrm{T}} &lt; 15\%, $$ {16} where $\pi$ is the rate of peritoneal closure at time of surgery for the appropriate treatment group. Unsuccessful peritoneal closure is defined as requiring the use of an alternative fixation device or additional procedure to achieve adequate fixation at time of surgery. The participating Investigators in the control arm in the study were able to use AbsorbaTack™, sutures or staples for closure of the peritoneum. With regards to safety, the following secondary endpoints were also evaluated during the study: - Quality of life experienced by subjects following groin hernia repair by LIQUIFIX FIX8™ or control as measured by the Carolinas Comfort Scale (CCS) at baseline (prior to surgery), and at 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, and 12 months following surgery. - Pain experienced following laparoscopic (TEP and TAPP) groin hernia repair by LIQUIFIX FIX8™ or control device, as measured by VAS at discharge, and at 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months following surgery. - Safety of LIQUIFIX FIX8™ and control device for groin hernia repair by comparing incidence of adverse events in patients post-laparoscopic groin hernia repair. ## B. Accountability of PMA Cohort At the time of database lock, of 284 patients enrolled in the PMA study, 93% (266) patients are available for analysis at the completion of the study, the Month 12 post-operative visit. In the ITT set analysis there was a total of 284 subjects included; 142 subjects were in the LIQUIFIX FIX8™ group and 142 subjects in the AbsorbaTack™ control group. In the PP set analysis, there was a total of 264 subjects: 131 subjects in the LIQUIFIX FIX8™ group and 133 subjects in the AbsorbaTack™ group. The accountability of all 284 ITT subjects enrolled in the study are presented in Table 7 below. PMA P220024: FDA Summary of Safety and Effectiveness Data 17 of 55 {17} Table 7: Randomized Subject Follow-up Accountability | Group | | | Pre-surgery | Surgery | Discharge | 1 Week | 2 Weeks | 1 Month | 3 Months | 6 Months | 9 Months | 12 Months | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | LIQUIFIX FIX8™ (N = 142) | Subject Follow-up | Eligible1 | 143 | 142 | 142 | 142 | 142 | 142 | 142 | 142 | 140 | 138 | | | | Clinical Follow-up Performed | 100.00% (143 / 143) | 100.00% (142 / 142) | 100.00% (142 / 142) | 97.89% (139 / 142) | 100.00% (142 / 142) | 97.18% (138 / 142) | 97.18% (138 / 142) | 95.77% (136 / 142) | 95.00% (133 / 140) | 95.65% (132 / 138) | | | Subject's Events Occurring Before Next Visit2 | Subject Screen Failure During Surgery | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | | | Subject Withdrew Consent | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | | | Sponsor's Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | | | Investigator's Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | | | Subject experienced an SAE that prevented attending all study visits | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | | | | Subject Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 6 | | | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | PMA P220024: FDA Summary of Safety and Effectiveness Data {18} Table 7: Randomized Subject Follow-up Accountability | Group | | | Pre-surgery | Surgery | Discharge | 1 Week | 2 Weeks | 1 Month | 3 Months | 6 Months | 9 Months | 12 Months | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | AbsorbaTackTM(N = 142) | Subject Follow-up | Eligible1 | 142 | 142 | 142 | 142 | 141 | 141 | 141 | 140 | 139 | 138 | | | | Clinical Follow-up Performed | 100.00% (142 / 142) | 100.00% (142 / 142) | 100.00% (142 / 142) | 98.59% (140 / 142) | 100.00% (141 / 141) | 97.16% (137 / 141) | 90.78% (128 / 141) | 95.00% (133 / 140) | 94.24% (131 / 139) | 97.10% (134 / 138) | | | Subject's Events Occurring Before Next Visit2 | Subject Screen Failure During Surgery | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | | | Subject Withdrew Consent | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | | | | Sponsor's Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | | | Investigator's Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | | | Subject experienced an SAE that prevented attending all study visits | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | | | Subject Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 4 | | | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | | 1Subjects are eligible if visit window opened prior to last follow-up date2Exits assigned to visit column where study exit date precedes the visit window close date and is later than the previous visit win dow close date. | | | | | | | | | | | | | # C. Study Population Demographics and Baseline Parameters The demographics of the study population are typical for a hernia repair study performed in the US. Most subjects were White 249, $88.0\%$ , male (270, $95.1\%$ ), and are more common with increasing age (mean: $58.94 \pm 14.041$ ), which is consistent with general hernia repair patient population. A total of 284 subjects were treated in a 1:1 ratio with 142 subjects treated to LIQUIFIX FIX8™ and 142 to control. Percentage comparisons between the control and treatment group showed no notable differences. When stratified by laparoscopic technique (TAPP/TEP), subjects were similar in age, gender, race and ethnicity, however, the Black or African American race was better represented in the PMA P220024: FDA Summary of Safety and Effectiveness Data {19} AbsorbaTack™ group treated by TAPP than by TEP technique (17.4% vs 0.0%). Subject demographics and baseline characteristics were well matched between arms. Table 8: Demographics (ITT set) | | LIQUIFIX FIX8™ (N = 142) | AbsorbaTack™ (N = 142) | All Subjects (N = 284) | | --- | --- | --- | --- | | Gender | | | | | Female | 7.0% (10 / 142) | 2.8% (4 / 142) | 4.9% (14 / 284) | | Male | 93.0% (132 / 142) | 97.2% (138 / 142) | 95.1% (270 / 284) | | Age (years) | | | | | n | 142 | 142 | 284 | | Mean ± SD | 59.41 ± 13.696 | 58.47 ± 14.411 | 58.94 ± 14.041 | | Median | 61.00 | 59.00 | 60.00 | | Min, Max | 22.0, 85.0 | 26.0, 89.0 | 22.0, 89.0 | | Race | | | | | American Indian or Alaska Native | 0.0% (0 / 142) | 0.0% (0 / 141) | 0.0% (0 / 283) | | Asian | 0.7% (1 / 142) | 2.1% (3 / 141) | 1.4% (4 / 283) | | Black or African American | 9.2% (13 / 142) | 11.3% (16 / 141) | 10.2% (29 / 283) | | More than One Race | 0.0% (0 / 142) | 0.7% (1 / 141) | 0.4% (1 / 283) | | Native Hawaiian or Other Pacific Islander | 0.0% (0 / 142) | 0.0% (0 / 141) | 0.0% (0 / 283) | | White | 90.1% (128 / 142) | 85.8% (121 / 141) | 88.0% (249 / 283) | | Ethnicity | | | | | Hispanic or Latino | 2.8% (4 / 142) | 2.8% (4 / 142) | 2.8% (8 / 284) | | Not Hispanic or Latino | 97.2% (138 / 142) | 97.2% (138 / 142) | 97.2% (276 / 284) | # D. Safety and Effectiveness Results # 1. Safety Results The analysis of safety was based on the LIQUIFIX FIX8™ (treatment) cohort of 142 patients. The key safety outcomes for this study are presented below in Tables 12 to 16. Adverse effects are reported in Tables 9 to 11. # Adverse effects that occurred in the PMA clinical study: A total of 271 adverse events (AEs) have been reported in the clinical study across the two treatment arms. A clinical event committee (CEC) has partaken in the review and adjudication of all adverse events during the Study. The incidence of device-related AEs by subject were comparable in the treatment (34 subjects; $23.9\%$ ) and control (43 subjects; $30.3\%$ ) groups. Out of these, 18 patients (6 Treatment, 12 Control) had more than one possibly device related AE. In terms of Serious AEs (SAEs), the incidence of possibly device-related adverse events was comparable between the treatment and control groups with 5 events in $5 - 3.5\%$ subjects of device related SAEs in the treatment group compared PMA P220024: FDA Summary of Safety and Effectiveness Data {20} to 4 events in $4 \times 2.8\%$ ) subjects in the control group. No single patient had more than one possibly device-related serious AE. Serious possibly device-related adverse events observed in the clinical study included neuralgia, hernia recurrence, mesh infection and intestinal obstruction. A summary of serious adverse events adjudicated by an independent Clinical Events Committee (CEC) as related to the device or procedure can be found in Table 10.1 below for the ITT population and Table 10.2 for the PP population. The percentage of Subjects with serious device and/or procedure related adverse events is similar across the ITT $(6.7\%)$ and PP $(6.8\%)$ population. There was a total 9 of possibly device related adverse events; 5 in the Table 9: AEs - Device and/or Procedure Related (ITT set) | | LIQUIFIX FIX8™ (N = 142) | | AbsorbaTack™ (N = 142) | | | --- | --- | --- | --- | --- | | # Serious Adverse Events (ITT) | N=11 | | N=16 | | | Total related to study device2 | 3.5% (5/142) | 5 | 2.8% (4/142) | 4 | | Total related to study procedure2 | 6.3% (9/142) | 9 | 7.0% (10/142) | 10 | | # Adverse Events (ITT) | N=114 | | N=157 | | | Total related to study device2 | 23.9% (34/142) | 41 | 30.3% (43/142) | 55 | | Total related to study procedure2 | 35.9% (51/142) | 76 | 43.0% (61/142) | 107 | | 2Related includes possibly and definitely related. | | | | | LIQUIFIX FIX8™ groups and 4 in the control tacker. The events in the LIQUIFIX FIX8™ group included two neuralgias, one recurrent hernia, one mesh infection and one small bowel obstruction. The control group possible device related adverse events included two hematoma which required further intervention, and two recurrent hernias. Specifically, the treatment group had two neuralgias which improved with time and on review of the clinical reporting form map of the site of application, the subject device was not applied on the nerves that were responsible for the neuralgias. In the single bowel obstruction, which occurred at an adhesion next to the cecum in an area where inadvertent device drop occurred, the study investigator could not conclusively attribute this adverse event to the subject device. Subsequent animal testing demonstrated that the subject device drops occurring outside the mesh area could be easily removed at any point after polymerization by peeling without incurring tissue damage. The tack control group experienced two hematomas and none were seen with the subject device. This was possibly device related and could be the result of the tissue penetrating mechanism of action associated with the control tacker. PMA P220024: FDA Summary of Safety and Effectiveness Data {21} Table 10.1: Serious AEs - Device and/or Procedure Related¹ (ITT) | | LIQUIFIX FIX8™ (N = 142) | | AbsorbaTack™ (N = 142) | | All Subjects (N = 284) | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event Term² | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | | Atrial fibrillation | 1 | 1 (0.7%) | 1 | 1 (0.7%) | 2 | 2 (0.7%) | | Hematoma | 0 | 0 (0.0%) | 2 | 2 (1.4%) | 2 | 2 (0.7%) | | Inguinal hernia | 1 | 1 (0.7%) | 1 | 1 (0.7%) | 2 | 2 (0.7%) | | Neuralgia | 2 | 2 (1.4%) | 0 | 0 (0.0%) | 2 | 2 (0.7%) | | Dizziness | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Hernia | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Incisional hernia | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Intestinal obstruction | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Medical device site infection | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4% | | Procedural pain | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Tooth abscess | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Urethral injury | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Urinary retention | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Urinary tract injury | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4% | | Vomiting | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Total | 9 | 9 (6.3%) | 10 | 10 (7.0%) | 19 | 19 (6.7%) | | ¹Related includes possibly and definitely related. ²Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term | | | | | | | Device and/or procedure related serious adverse events for the PP population has been presented in Table 10.2 below. Table 10.2: Serious AEs - Device and/or Procedure Related¹ (PP) | | LIQUIFIX FIX8™ (N = 131) | | AbsorbaTack™ (N = 133) | | All Subjects (N = 264) | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event Term² | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | | Hematoma | 0 | 0 (0.0%) | 2 | 2 (1.5%) | 2 | 2 (0.8%) | | Inguinal hernia | 1 | 1 (0.8%) | 1 | 1 (0.8%) | 2 | 2 (0.8%) | | Neuralgia | 2 | 2 (1.5%) | 0 | 0 (0.0%) | 2 | 2 (0.8%) | | Atrial fibrillation | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Dizziness | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Hernia | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Incisional hernia | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Intestinal obstruction | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | PMA P220024: FDA Summary of Safety and Effectiveness Data 22 of 55 {22} Table 10.2: Serious AEs - Device and/or Procedure Related¹ (PP) | | LIQUIFIX FIX8™ (N = 131) | | AbsorbaTack™ (N = 133) | | All Subjects (N = 264) | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event Term² | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | | Medical device site infection | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Procedural pain | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Tooth abscess | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Urethral injury | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Urinary retention | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Urinary tract injury | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Vomiting | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Total | 9 | 9 (6.9%) | 9 | 9 (6.8%) | 18 | 18 (6.8%) | | ¹Related includes possibly and definitely related. ²MedDRA Preferred Term | | | | | | | The majority of non-serious device and/or procedure related adverse events were seroma formation. Overall, there were 47 events related to seroma in 44 (15.5%) subjects. All cases were mild in severity, and none were considered only related to the device in both groups. Other notable frequent non-serious AEs were groin pain with 16 events (16 subjects; 5.6%) and urinary retention with 10 events (10; 3.5%). Possibly related non-serious AEs were comparable between groups with the following notable differences: the incidence of seroma (13.4% Treatment, 17.6% Control) and groin pain (2.8% Treatment, 8.5% Control) was lower in the treatment group. A summary of non-serious adverse events adjudicated by the CEC as possibly or definitely related to the device or procedure can be found in Table 11.1 below for the ITT population and Table 11.2 for the PP population. The percentage of Subjects with non-serious device and/or procedure related adverse events is similar across the ITT (36.3%) and PP (36.0%) population. Table 11.1: Non-Serious AEs - Device and/or Procedure Related¹ (ITT) | | LIQUIFIX FIX8™ (N = 142) | | AbsorbaTack™ (N = 142) | | All Subjects (N = 284) | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event Term² | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | | Seroma | 20 | 19 13.4% | 27 | 25 17.6% | 47 | 44 15.5% | | Groin pain | 4 | 4 (2.8%) | 12 | 12 (8.5%) | 16 | 16 (5.6%) | | Urinary retention | 5 | 5 (3.5%) | 5 | 5 (3.5%) | 10 | 10 (3.5%) | | Post procedural constipation | 4 | 4 (2.8%) | 3 | 3 (2.1%) | 7 | 7 (2.5%) | | Dysuria | 2 | 2 (1.4%) | 3 | 3 (2.1%) | 5 | 5 (1.8%) | | Hematoma | 2 | 2 (1.4%) | 3 | 3 (2.1%) | 5 | 5 (1.8%) | | Procedural nausea | 0 | 0 (0.0%) | 5 | 5 (3.5%) | 5 | 5 (1.8%) | PMA P220024: FDA Summary of Safety and Effectiveness Data 23 of 55 {23} Table 11.1: Non-Serious AEs - Device and/or Procedure Related¹ (ITT) | | LIQUIFIX FIX8™ (N = 142) | | AbsorbaTack™ (N = 142) | | All Subjects (N = 284) | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event Term² | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | | Testicular pain | 3 | 3 (2.1%) | 2 | 2 (1.4%) | 5 | 5 (1.8%) | | Musculoskeletal pain | 4 | 4 (2.8%) | 0 | 0 (0.0%) | 4 | 4 (1.4%) | | Pain | 1 | 1 (0.7%) | 3 | 2 (1.4%) | 4 | 3 (1.1%) | | Swelling | 1 | 1 (0.7%) | 3 | 2 (1.4%) | 4 | 3 (1.1%) | | Genital hemorrhage | 2 | 2 (1.4%) | 1 | 1 (0.7%) | 3 | 3 (1.1%) | | Cellulitis | 1 | 1 (0.7%) | 1 | 1 (0.7%) | 2 | 2 (0.7%) | | Hypoaesthesia | 1 | 1 (0.7%) | 1 | 1 (0.7%) | 2 | 2 (0.7%) | | Orchitis | 1 | 1 (0.7%) | 1 | 1 (0.7%) | 2 | 2 (0.7%) | | Post procedural hematuria | 0 | 0 (0.0%) | 2 | 2 (1.4%) | 2 | 2 (0.7%) | | Rash | 0 | 0 (0.0%) | 2 | 2 (1.4%) | 2 | 2 (0.7%) | | Spermatic cord inflammation | 1 | 1 (0.7%) | 1 | 1 (0.7%) | 2 | 2 (0.7%) | | Umbilical hernia | 1 | 1 (0.7%) | 1 | 1 (0.7%) | 2 | 2 (0.7%) | | Urinary retention postoperative | 0 | 0 (0.0%) | 2 | 2 (1.4%) | 2 | 2 (0.7%) | | Abdominal pain | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Abdominal pain lower | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Arthralgia | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Back pain | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Burning sensation | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Change of bowel habit | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Constipation | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Dermatitis contact | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Diarrhea | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Dyspepsia | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Flatulence | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Gastrointestinal procedural complication | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Incisional hernia | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Inguinal mass | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Injection site hematoma | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Lymphadenitis | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Muscle strain | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Musculoskeletal chest pain | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Neuralgia | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Nodule | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Pollakiuria | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | PMA P220024: FDA Summary of Safety and Effectiveness Data 24 of 55 {24} Table 11.1: Non-Serious AEs - Device and/or Procedure Related¹ (ITT) | | LIQUIFIX FIX8™ (N = 142) | | AbsorbaTack™ (N = 142) | | All Subjects (N = 284) | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event Term² | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | | Postoperative wound infection | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Reflex test abnormal | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Scrotal hematoma | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Scrotal pain | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Testicular swelling | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Throat irritation | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Urethral pain | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Urinary incontinence | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Urinary tract infection | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Urinary tract procedural complication | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Vomiting | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Wound dehiscence | 0 | 0 (0.0%) | 1 | 1 (0.7%) | 1 | 1 (0.4%) | | Total | 67 | 46 32.4% | 97 | 57 40.1% | 164 | 103 (36.3%) | | ¹Related includes possibly and definitely related. ²MedDRA Preferred Term | | | | | | | Table 11.2: Non-Serious AEs - Device and/or Procedure Related¹ (PP) | | LIQUIFIX FIX8™ (N = 131) | | AbsorbaTack™ (N = 133) | | All Subjects (N = 264) | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event Term² | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | | Seroma | 18 | 17 13.0% | 26 | 24 18.0% | 44 | 41 15.5% | | Groin pain | 4 | 4 (3.1%) | 10 | 10 (7.5%) | 14 | 14 (5.3%) | | Urinary retention | 5 | 5 (3.8%) | 5 | 5 (3.8%) | 10 | 10 (3.8%) | | Post procedural constipation | 4 | 4 (3.1%) | 3 | 3 (2.3%) | 7 | 7 (2.7%) | | Dysuria | 2 | 2 (1.5%) | 3 | 3 (2.3%) | 5 | 5 (1.9%) | | Procedural nausea | 0 | 0 (0.0%) | 5 | 5 (3.8%) | 5 | 5 (1.9%) | | Hematoma | 1 | 1 (0.8%) | 3 | 3 (2.3%) | 4 | 4 (1.5%) | | Musculoskeletal pain | 4 | 4 (3.1%) | 0 | 0 (0.0%) | 4 | 4 (1.5%) | | Pain | 1 | 1 (0.8%) | 3 | 2 (1.5%) | 4 | 3 (1.1%) | | Testicular pain | 3 | 3 (2.3%) | 1 | 1 (0.8%) | 4 | 4 (1.5%) | | Genital hemorrhage | 2 | 2 (1.5%) | 1 | 1 (0.8%) | 3 | 3 (1.1%) | | Cellulitis | 1 | 1 (0.8%) | 1 | 1 (0.8%) | 2 | 2 (0.8%) | | Hypoaesthesia | 1 | 1 (0.8%) | 1 | 1 (0.8%) | 2 | 2 (0.8%) | PMA P220024: FDA Summary of Safety and Effectiveness Data {25} Table 11.2: Non-Serious AEs - Device and/or Procedure Related¹ (PP) | | LIQUIFIX FIX8™ (N = 131) | | AbsorbaTack™ (N = 133) | | All Subjects (N = 264) | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event Term² | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | | Orchitis | 1 | 1 (0.8%) | 1 | 1 (0.8%) | 2 | 2 (0.8%) | | Post procedural haematuria | 0 | 0 (0.0%) | 2 | 2 (1.5%) | 2 | 2 (0.8%) | | Rash | 0 | 0 (0.0%) | 2 | 2 (1.5%) | 2 | 2 (0.8%) | | Spermatic cord inflammation | 1 | 1 (0.8%) | 1 | 1 (0.8%) | 2 | 2 (0.8%) | | Swelling | 1 | 1 (0.8%) | 1 | 1 (0.8%) | 2 | 2 (0.8%) | | Umbilical hernia | 1 | 1 (0.8%) | 1 | 1 (0.8%) | 2 | 2 (0.8%) | | Urinary retention postoperative | 0 | 0 (0.0%) | 2 | 2 (1.5%) | 2 | 2 (0.8%) | | Abdominal pain | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Abdominal pain lower | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Arthralgia | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Back pain | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Burning sensation | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Constipation | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Dermatitis contact | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Diarrhea | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Dyspepsia | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Flatulence | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Gastrointestinal procedural complication | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Incisional hernia | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Inguinal mass | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Injection site hematoma | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Lymphadenitis | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Muscle strain | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Musculoskeletal chest pain | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Neuralgia | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Nodule | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Pollakiuria | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Postoperative wound infection | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Reflex test abnormal | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Scrotal hematoma | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Scrotal pain | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Testicular swelling | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Throat irritation | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | PMA P220024: FDA Summary of Safety and Effectiveness Data 26 of 55 {26} Table 11.2: Non-Serious AEs - Device and/or Procedure Related¹ (PP) | | LIQUIFIX FIX8™ (N = 131) | | AbsorbaTack™ (N = 133) | | All Subjects (N = 264) | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event Term² | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | Number of Events | Number (%) of Subjects with Events | | Urethral pain | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Urinary incontinence | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Urinary tract infection | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Urinary tract procedural complication | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Vomiting | 1 | 1 (0.8%) | 0 | 0 (0.0%) | 1 | 1 (0.4%) | | Wound dehiscence | 0 | 0 (0.0%) | 1 | 1 (0.8%) | 1 | 1 (0.4%) | | Total | 64 | 43 32.8% | 90 | 52 39.1% | 154 | 95 36.0% | | ¹Related includes possibly and definitely related. ²MedDRA Preferred Term | | | | | | | ## 2. Effectiveness Results Of the 284 patients randomized, the analysis of key (primary) effectiveness was based on 131/131 subjects in the LIQUIFIX FIX8™ treatment arm and 130/133 evaluable patients in the Control arm (in the PP completers dataset) and 269/284 patients (in the ITT completers dataset). The results are based on the 6-month follow-up completers for both the PP and ITT population. Primary effectiveness outcomes are presented in Table 12. Secondary effectiveness outcomes are presented in Table 13 to Table 15. **Primary Effectiveness: Change in VAS from baseline to 6 months post-hernia repair** Subjects were considered enrolled in the study once they were randomized. All randomized subjects are included in the intent-to-treat (ITT) population and analyzed according to the treatment to which they were randomized. Additional analyses were performed on the per-protocol (PP) population. The PP population included all subjects treated as randomized who do not have major protocol violations. The mean change in VAS pain score as measured from 6 months compared to baseline (worst pain experienced within 1 month of screening visit) for LIQUIFIX FIX8™ was -4.9 ± 2.5 and the control was -5.1 ± 2.3 for both the PP and ITT population. Non-inferiority of LIQUIFIX FIX8™ versus AbsorbaTack™ was demonstrated since the upper limits of the two-sided 95% CI based on PP and ITT completers for the difference in the mean change in VAS pain score as measured from 6 months compared to baseline were less than the predefined non-inferiority margin set at 0.9. The missing data rate for primary effectiveness endpoint was 1.14% (3 Subjects) for the PP population and 5.28% (15 Subjects) for the ITT population. PMA P220024: FDA Summary of Safety and Effectiveness Data {27} Table 12.1: Primary effectiveness endpoint: Change in VAS from baseline¹ to 6 months post hernia repair in subjects requiring laparoscopic TEP and TAPP hernia repair (PP set) | | LIQUIFIX FIX8™ (N = 131) | AbsorbaTack™ (N = 133) | Difference² | p-value³ | Non-inferior (Yes/No)⁴ | | --- | --- | --- | --- | --- | --- | | n | 131 | 130 | | | Yes | | Mean ± SD | -4.9 ± 2.5 | -5.1 ± 2.3 | | | | | Median | -4.7 | -5.0 | | | | | Min, Max | -10.0, 2.0 | -10.0, -0.5 | | | | | Least Squares Mean | | | 0.22 | 0.011 | | | 95% CI | | | -0.36, 0.80 | | | | Note: The denominator is the number of evaluable data points and may be less than the analysis population size due to missing data. ¹ Worst pain experienced within 1 month of screening visit ² LIQUIFIX FIX8™ - AbsorbaTack™ ³ One-sided p-value (Difference < 0.9), based on general linear model for treatment arm adjusted for laparoscopic repair technique with non-inferiority margin of 0.9 ⁴ Indicated by p-value < 0.025 | | | | | | Table 12.2: Primary efficacy endpoint: Change in VAS from baseline¹ to 6 months post hernia repair in subjects requiring laparoscopic TEP and TAPP hernia repair (ITT set) | | LIQUIFIX FIX8™ (N = 142) | AbsorbaTack (N = 142) | Difference² | p-value³ | Non-inferior (Yes/No)⁴ | | --- | --- | --- | --- | --- | --- | | n | 136 | 133 | | | Yes | | Mean ± SD | -4.9 ± 2.5 | -5.1 ± 2.3 | | | | | Median | -4.5 | -5.0 | | | | | Min, Max | -10.0, 2.0 | -10.0, -0.5 | | | | | Least Squares Mean | | | 0.25 | 0.013 | | | 95% CI | | | -0.33, 0.82 | | | | Note: The denominator is the number of evaluable data points and may be less than the analysis population size due to missing data. ¹ Worst pain experienced within 1 month of screening visit ² LIQUIFIX FIX8™ - AbsorbaTack™ ³ One-sided p-value (Difference < 0.9), based on general linear model for treatment arm adjusted for laparoscopic repair technique with non-inferiority margin of 0.9 ⁴ Indicated by p-value < 0.025 | | | | | | ## Hypothesis Tested Secondary Effectiveness Endpoint Results ## Hernia Recurrence at 6 months A total of three (3) hernia recurrences were recorded in the clinical study; one for LIQUIFIX FIX8™ and two (2) for Control. Non-inferiority of LIQUIFIX FIX8™ versus AbsorbaTack™ was demonstrated since the upper limits of the two-sided 95% CI based on PP and ITT completers for the difference in hernia recurrence as measured from 6 months were less than the pre-defined non-inferiority margin set at 10%. The missing data rate for secondary effectiveness endpoint hernia recurrence was 0.38% (1 Subject) for the PP population and 1.06% (3 Subjects) for the ITT population. PMA P220024: FDA Summary of Safety and Effectiveness Data {28} Table 13.1: Secondary effectiveness endpoint 1: Hernia Recurrence rate at 6 months in subjects following TEP and TAPP groin hernia repair (PP set) | | LIQUIFIX FIX8 (N = 131 Subjects) | AbsorbaTack (N = 133 Subjects) | Difference1 | p-value2 | Non-inferior (Yes/No)3 | | --- | --- | --- | --- | --- | --- | | % (n/N | 0.8% (1/131) | 1.5% (2/132) | -0.8% | <0.001 | Yes | | 95% CI | 0.0%, 2.3% | 0.0%, 3.6% | -3.3%, 1.8% | | | | Note: The denominator is the number of evaluable data points and may be less than the analysis population size due to missing data. Note: Denominator includes subjects with hernia recurrence by visit or follow-up through the visit window open date. 1 LIQUIFIX FIX8 - AbsorbaTack. 2 Based on a Non-inferiority Farrington-Manning test with a 10% margin 3 Indicated by Upper CI Limit < 10% | | | | | | Table 13.2: Secondary Effectiveness Endpoint 1: Hernia recurrence rate at 6 months in subjects following TEP and TAPP groin hernia repair (ITT set) | | LIQUIFIX FIX8™ (N = 142 Subjects) | AbsorbaTack™ (N = 142 Subjects) | Difference1 | p-value2 | Non-inferior (Yes/No)3 | | --- | --- | --- | --- | --- | --- | | % (n/N | 0.7% (1/141) | 1.4% (2/140) | -0.7% | <0.001 | Yes | | 95% CI | 0.0%, 2.1% | 0.0%, 3.4% | -3.1%, 1.7% | | | | Note: Denominator includes subjects with hernia recurrence by visit or follow-up through the visit window open date Note: The denominator is the number of evaluable data points and may be less than the analysis population size due to missing data.. 1 LIQUIFIX FIX8™ - AbsorbaTack™. 2 Based on a Non-inferiority Farrington-Manning test with a 10% margin 3 Indicated by Upper CI Limit < 10% | | | | | | Recurrence rates up to 12-month follow-up have been presented in Table 13.3 below. There were no additional occurrences of recurrence after 6-month follow-up. Table 13.3: Secondary endpoint: Hernia Recurrence rate $^{1}$ at 2 weeks, 3 months, 6 months, 9 months, and 12 months in subjects following TEP and TAPP groin hernia repair (ITT set) | Visit | LIQUIFIX FIX8™ (N = 142) | AbsorbaTack™ (N = 142) | | --- | --- | --- | | 2 weeks | 0.0% (0/142) | 0.0% (0/141) | | 3 months | 0.7% (1/142) | 0.7% (1/141) | | 6 months | 0.7% (1/141) | 1.4% (2/140) | | 9 months | 0.7% (1/139) | 1.4% (2/138) | | 12 months | 0.8% (1/133) | 1.5% (2/135) | | 1 Rates are cumulative. Subjects having hernia recurrence at earlier timepoints are carried forward to later dates. Denominator includes subjects with hernia recurrence by visit, confirmed visit attendance, and/or follow-up through the visit window open date. | | | Hernia Mesh Fixation at time of surgery Both arms (treatment and control) achieved $100\%$ successful mesh fixation at time of surgery. LIQUIFIX FIX8™ was considered non-inferior to Control device in both the ITT and PP completers at the Subject Level analysis. PMA P220024: FDA Summary of Safety and Effectiveness Data {29} Non-inferiority of LIQUIFIX FIX8™ versus AbsorbaTack™ was demonstrated since the lower limits of the two-sided 95% CI based on PP and ITT completers for the difference in hernia mesh fixation at time of surgery were greater than the pre-defined non-inferiority margin set at -10%. The missing data rate for secondary effectiveness endpoint hernia mesh fixation was 0% for both the PP population and ITT population. Table 14.1: Secondary effectiveness endpoint 2: Rate of successful hernia mesh fixation in subjects undergoing TEP and TAPP laparoscopic groin hernia repair (PP set) Assessed Per-Subject | | LIQUIFIX FIX8™ (N = 180 Hernias N = 131 Subjects) | AbsorbaTack™ (N = 193 Hernias N = 133 Subjects) | Difference¹ | p-value² | Non-inferior (Yes/No)³ | | --- | --- | --- | --- | --- | --- | | % (n/N) | 100.0% (131/131) | 100.0% (133/133) | -0.0% | <0.001 | Yes | | 95% CI | 100.0%, 100.0% | 100.0%, 100.0% | -0.1%, 0.1% | | | | Note: The denominator is the number of evaluable data points and may be less than the analysis population size due to missing data. ¹ LIQUIFIX FIX8™ - AbsorbaTack™. ² Based on a Non-inferiority Farrington-Manning test with a 10% margin. 0.001 added to zero-cells to calculate CI and p-value. ³ Indicated by Lower CI Limit > -10% | | | | | | Table 14.2: Secondary effectiveness endpoint 2: Rate of successful hernia mesh fixation in subjects undergoing TEP and TAPP laparoscopic groin hernia repair (ITT set) Assessed Per-Subject | | LIQUIFIX FIX8™ (N = 195 Hernias N = 142 Subjects) | AbsorbaTack™ (N = 204 Hernias N = 142 Subjects) | Difference¹ | p-value² | Non-inferior (Yes/No)³ | | --- | --- | --- | --- | --- | --- | | % (n/N) | 100.0% (142/142) | 100.0% (142/142) | 0.0% | <0.001 | Yes | | 95% CI | 100.0%, 100.0% | 100.0%, 100.0% | -0.1%, 0.1% | | | | Note: The denominator is the number of evaluable data points and may be less than the analysis population size due to missing data. ¹ LIQUIFIX FIX8™ - AbsorbaTack™. ² Based on a Non-inferiority Farrington-Manning test with a 10% margin. 0.001 added to zero-cells to calculate CI and p-value. ³ Indicated by Lower CI Limit > -10% | | | | | | ## Peritoneal Closure at time of surgery (TAPP repairs only) LIQUIFIX FIX8™ achieved an 88.4% peritoneal closure success rate in comparison to the Control arm’s 90.5% when assessed at the Subject Level. Non-inferiority of LIQUIFIX FIX8™ versus AbsorbaTack™ was demonstrated since the lower limits of the two-sided 95% CI based on PP and ITT completers for the difference in peritoneal closure at time of surgery were greater than the pre-defined non-inferiority margin set at -15%. The missing data rate for secondary effectiveness endpoint peritoneal closure at time of surgery was 0% for both the PP and ITT population. PMA P220024: FDA Summary of Safety and Effectiveness Data 30 of 55 {30} Table 15.1: Secondary effectiveness endpoint 3: Rate of successful peritoneal closure in subjects undergoing laparoscopic TAPP hernia repair (PP set) Assessed Per-Subject | | LIQUIFIX FIX8™ (N = 108 Hernias N = 86 Subjects) | AbsorbaTack™ (N = 112 Hernias N = 84 Subjects) | Difference1 | p-value2 | Non-inferior (Yes/No)3 | | --- | --- | --- | --- | --- | --- | | % (n/N) | 88.4% (76/86) | 90.5% (76/84) | -2.1% | 0.006 | Yes | | 95% CI | 81.6%, 95.1% | 84.2%, 96.8% | -11.4%, 7.1% | | | | Note: The denominator is the number of evaluable data points and may be less than the analysis population size due to missing data. 1 LIQUIFIX FIX8™- AbsorbaTack™. 2 Based on a Non-inferiority Farrington-Manning test with a 15% margin 3 Indicated by Lower CI Limit > -15% | | | | | | Table 15.2: Secondary effectiveness endpoint 3: Rate of successful peritoneal closure in subjects undergoing laparoscopic TAPP hernia repair (ITT set) Assessed Per-Subject | | LIQUIFIX FIX8™ (N = 117 Hernias N = 94 Subjects) | AbsorbaTack™ (N = 122 Hernias N = 92 Subjects) | Difference1 | p-value2 | Non-inferior (Yes/No)3 | | --- | --- | --- | --- | --- | --- | | % (n/N) | 87.2% (82/94) | 91.3% (84/92) | -4.1% | 0.012 | Yes | | 95% CI | 80.5%, 94.0% | 85.5%, 97.1% | -13.0%, 4.8% | | | | Note: The denominator is the number of evaluable data points and may be less than the analysis population size due to missing data. 1 LIQUIFIX FIX8™- AbsorbaTack™. 2 Based on a Non-inferiority Farrington-Manning test with a 15% margin 3 Indicated by Lower CI Limit > -15% | | | | | | ## Ancillary Secondary Effectiveness Endpoint Results ## Quality of Life (Carolina Comfort Scale) Quality of Life (QOL) was assessed at each post-operative follow-up visit using a Carolina Comfort Scale questionnaire which assessed pain, sensation of mesh and movement limitations over various activities. A scale of 0 (No symptoms) to 5 (Disabling symptoms) is used to record subject Quality of Life. The accumulative total score can range from 0 to 115 with the higher the score the lower the health-related quality of life. Numerical improvement was observed for comparison of QOL at 12-month post-operative versus 1-week post-surgery, with a mean change of $-15.6 \pm 16.0$ for LIQUIFIX FIX8™ and $-15.3 \pm 16.1$ for control. PMA P220024: FDA Summary of Safety and Effectiveness Data {31} Table 16: Secondary endpoint: Carolinas Comfort Scale (CCS) Questionnaire Total Score at 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months (ITT set) | | LIQUIFIX FIX8 (N = 142) | | AbsorbaTack (N = 142) | | | --- | --- | --- | --- | --- | | | Total Score n Mean ± SD Median (p25, p75) Min, Max | Change from 1 week n Mean ± SD Median (p25, p75) Min, Max | Total Score n Mean ± SD Median (p25, p75) Min, Max | Change from 1 week n Mean ± SD Median (p25, p75) Min, Max | | 1 week | 129 | N/A | 129 | N/A | | | 16.1 ± 15.7 | | 16.9 ± 16.6 | | | | 12.0 (5.0, 22.0) | | 13.0 (5.0, 24.0) | | | | 0.0, 83.0 | | 0.0, 80.0 | | | 2 weeks | 136 | 126 | 137 | 128 | | | 8.6 ± 13.2 | -7.7 ± 12.4 | 10.2 ± 15.2 | -7.0 ± 13.2 | | | 3.0 (0.0, 11.5) | -5.0 (-13.0, 0.0) | 4.0 (1.0, 12.0) | -5.0 (-11.0, -1.0) | | | 0.0, 64.0 | -55.0, 26.0 | 0.0, 77.0 | -61.0, 47.0 | | 1 month | 136 | 125 | 134 | 124 | | | 4.8 ± 8.2 | -12.4 ± 12.6 | 5.2 ± 10.5 | -12.2 ± 14.6 | | | 2.0 (0.0, 6.0) | -9.0 (-18.0, -3.0) | 1.0 (0.0, 5.0) | -9.0 (-17.5, -3.0) | | | 0.0, 53.0 | -55.0, 12.0 | 0.0, 82.0 | -75.0, 41.0 | | 3 months | 137 | 124 | 126 | 117 | | | 2.0 ± 7.6 | -14.6 ± 16.9 | 2.7 ± 8.5 | -14.4 ± 15.9 | | | 0.0 (0.0, 1.0) | -11.0 (-20.5, -4.0) | 0.0 (0.0, 2.0) | -10.0 (-21.0, -3.0) | | | 0.0, 75.0 | -83.0, 47.0 | 0.0, 69.0 | -79.0, 28.0 | | 6 months | 136 | 123 | 133 | 122 | | | 1.2 ± 3.8 | -15.1 ± 16.0 | 1.8 ± 4.4 | -15.3 ± 16.7 | | | 0.0 (0.0, 0.0) | -12.0 (-22.0, -3.0) | 0.0 (0.0, 1.0) | -11.0 (-23.0, -4.0) | | | 0.0, 24.0 | -83.0, 15.0 | 0.0, 35.0 | -80.0, 24.0 | | 9 months | 133 | 123 | 130 | 120 | | | 0.9 ± 3.1 | -15.6 ± 16.3 | 1.4 ± 3.8 | -15.7 ± 16.5 | | | 0.0 (0.0, 0.0) | -12.0 (-24.0, -4.0) | 0.0 (0.0, 1.0) | -11.0 (-22.0, -4.5) | | | 0.0, 29.0 | -83.0, 24.0 | 0.0, 27.0 | -80.0, 14.0 | | 12 months | 131 | 120 | 133 | 122 | | | 0.5 ± 1.5 | -15.6 ± 16.0 | 0.8 ± 3.5 | -15.3 ± 16.1 | | | 0.0 (0.0, 0.0) | -11.0 (-23.0, -4.5) | 0.0 (0.0, 0.0) | -11.0 (-22.0, -4.0) | | | 0.0, 11.0 | -83.0, 6.0 | 0.0, 34.0 | -80.0, 23.0 | | If more than 2 patient responses within a domain were missing, then the summary score is set to missing. Otherwise mean imputation is used for missing responses. Score unable to be calculated prior to surgery because patient has not had hernia repair. | | | | | ## Pain (VAS) Pain was assessed at each post-operative follow-up visit using a VAS scale tool. The results of the primary effectiveness endpoint of change in VAS pain at 6-month from baseline is described above. Numerical reduction was observed in the results from the 12-month follow-up period, with LIQUIFIX FIX8™ mean change of $-3.6 \pm 2.9$ (N=132) and Control $-3.5 \pm 3.1$ (N=133) for the ITT completers. PMA P220024: FDA Summary of Safety and Effectiveness Data {32} Table 17: Secondary endpoint: VAS at pre-surgery, discharge, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, and 12 months (ITT set) | | LIQUIFIX FIX8™ (N = 142) | | AbsorbaTack™ (N = 142) | | | --- | --- | --- | --- | --- | | | VAS n Mean ± SD Median (p25, p75) Min, Max | VAS Change from Pre- Surgery n Mean ± SD Median (p25, p75) Min, Max | VAS n Mean ± SD Median (p25, p75) Min, Max | VAS Change from Pre- Surgery n Mean ± SD Median (p25, p75) Min, Max | | Pre-surgery | 142 | N/A | 142 | N/A | | | 3.8 ± 2.9 | | 3.8 ± 3.0 | | | | 3.3 (1.5, 6.0) | | 3.0 (1.0, 6.5) | | | | 0.0, 10.0 | | 0.0, 10.0 | | | Discharge | 142 | 142 | 142 | 142 | | | 3.5 ± 2.1 | -0.3 ± 3.4 | 3.7 ± 1.9 | -0.1 ± 3.5 | | | 3.5 (2.0, 5.0) | 0.0 (-3.0, 2.0) | 4.0 (2.0, 5.0) | 0.0 (-3.0, 2.9) | | | 0.0, 10.0 | -8.2, 6.5 | 0.0, 10.0 | -8.0, 7.0 | | 1 week | 139 | 139 | 140 | 140 | | | 2.3 ± 1.9 | -1.5 ± 2.8 | 2.3 ± 1.9 | -1.5 ± 3.1 | | | 2.0 (1.0, 3.5) | -1.0 (-3.9, 0.5) | 2.0 (1.0, 3.5) | -1.0 (-3.3, 1.0) | | | 0.0, 9.0 | -10.0, 4.0 | 0.0, 7.0 | -10.0, 7.0 | | 2 weeks | 141 | 141 | 141 | 141 | | | 1.0 ± 1.4 | -2.8 ± 2.8 | 1.1 ± 1.3 | -2.7 ± 2.9 | | | 0.5 (0.0, 1.5) | -2.0 (-4.9, -0.9) | 1.0 (0.0, 2.0) | -2.0 (-5.0, -0.5) | | | 0.0, 8.0 | -10.0, 2.1 | 0.0, 6.0 | -9.5, 4.0 | | 1 month | 138 | 138 | 137 | 137 | | | 0.6 ± 1.0 | -3.2 ± 2.8 | 0.7 ± 1.2 | -3.1 ± 3.1 | | | 0.0 (0.0, 1.0) | -2.8 (-5.1, -0.9) | 0.0 (0.0, 1.0) | -2.5 (-5.5, -1.0) | | | 0.0, 5.0 | -10.0, 1.0 | 0.0, 7.0 | -10.0, 6.5 | | 3 months | 138 | 138 | 129 | 129 | | | 0.2 ± 0.7 | -3.6 ± 2.9 | 0.4 ± 0.9 | -3.4 ± 3.1 | | | 0.0 (0.0, 0.0) | -3.0 (-6.0, -1.0) | 0.0 (0.0, 0.0) | -2.1 (-6.0, -1.0) | | | 0.0, 5.2 | -10.0, 1.0 | 0.0, 7.0 | -10.0, 3.0 | | 6 months | 136 | 136 | 133 | 133 | | | 0.2 ± 0.8 | -3.6 ± 3.0 | 0.3 ± 0.7 | -3.5 ± 3.1 | | | 0.0 (0.0, 0.0) | -3.0 (-6.0, -1.0) | 0.0 (0.0, 0.0) | -3.0 (-6.0, -1.0) | | | 0.0, 6.0 | -10.0, 3.0 | 0.0, 4.0 | -10.0, 2.0 | | 9 months | 133 | 133 | 131 | 131 | | | 0.1 ± 0.3 | -3.7 ± 2.9 | 0.2 ± 0.6 | -3.5 ± 3.0 | | | 0.0 (0.0, 0.0) | -3.0 (-6.0, -1.4) | 0.0 (0.0, 0.0) | -3.0 (-6.0, -1.0) | | | 0.0, 2.0 | -10.0, 1.0 | 0.0, 3.5 | -10.0, 1.0 | | 12 months | 132 | 132 | 133 | 133 | | | 0.1 ± 0.4 | -3.6 ± 2.9 | 0.1 ± 0.6 | -3.5 ± 3.1 | | | 0.0 (0.0, 0.0) | -3.0 (-6.0, -1.0) | 0.0 (0.0, 0.0) | -3.0 (-6.0, -1.0) | | | 0.0, 3.0 | -10.0, 0.0 | 0.0, 6.0 | -10.0, 6.0 | PMA P220024: FDA Summary of Safety and Effectiveness Data {33} # 3. Subgroup Analyses The following pre-operative characteristics were evaluated for potential association with outcomes: Size of hernia &lt;3cm or ≥3cm), Sex of subject M or F, Age of subject (in years – Dichotomized at Median Age, Femoral or Inguinal groin hernia, Direct or indirect groin hernia, Primary or recurrent groin hernia, Unilateral or bilateral…
Innolitics

Panel 1

/
Sort by
Ready

Predicate graph will load when search results are available.

Embedding visualization will load when search results are available.

PDF viewer will load when search results are available.

Loading panels...

Select an item from Submissions

Click any panel, subpart, regulation, product code, or device to see details here.

Section Matches

Results will appear here.

Product Code Matches

Results will appear here.

Special Control Matches

Results will appear here.

Loading collections...