A Prospective, Randomized, Controlled Multi-center Study of ArtiFascia® Dural Repair Patch Compared With Commercially Available Dural Substitutes. To Evaluate the Safety and Effectiveness of ArtiFascia® in Subjects Requiring Dural Repair.

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and effectiveness of ArtiFascia® in comparison with commercially available dural substitutes in patients requiring Dural repair following neurosurgery. Patients with planned cranial neurosurgery can take part in this study. During the surgery the soft membrane that covers the brain (called dura) is likely to be cut and damaged. A damaged dura can cause a leakage of brain fluids (cerebrospinal fluid [CSF] leakage) and increase the risk of infections. Sponsor of this study has developed the ArtiFascia®. ArtiFascia® is a medical synthetic dural substitute that is absorbed by the body. ArtiFascia® supports the re-formation of a new dura. In addition it has a sealant layer that can reduce CSF leakage and infection.

Detailed Description
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A Prospective, randomized, controlled multi-center study of ArtiFascia® Dural repair patch compared with commercially available dural substitutes- NEOART Study. The dura mater is a fibrous connective tissue that surrounds the nervous system (brain and spinal cord) and provides a mechanical barrier that contains the cerebrospinal fluid (CSF). The dura mater may be damaged as a result of trauma or planned surgery. When dural defects cannot be repaired by primary closure, a dural substitute must be utilized in order to reduce CSF leakage. There are devices that have been used as dural substitutes. Among the devices that are based on natural raw materials, collagen-based matrices are widely used. Although collagen was proven to be biocompatible, using collagen-based materials still possess several limitations such as CSF leaks. Synthetic dural substitutes are also used to repair dura mater. The most widely used raw-material for these synthetic products are polyesters - resorbable and biocompatible polymers. There are several dural substitutes based on synthetic polyesters that were successfully tested pre-clinically as well as in human studies. Sponsor of this study has developed the ArtiFascia®. ArtiFascia® is a medical synthetic dural substitute that is absorbed by the body. Before the study, the patients will have their blood taken and they will undergo neurological assessment. If they are suitable to participate in the study, and agree to participate, they will be randomly allocated into one of the following groups: Experimental group (ArtiFascia® device); Control group (Other commercially available suturable dural substitutes). The patients will undergo a surgery that is identical to the one that was planned by the surgeon. At the end of the surgery, the investigator will use ArtiFascia® patch or standard dural substitute to repair the damaged Dura. ArtiFascia® graft will be placed in areas where the native dural layer was damaged or missing. ArtiFascia® will be applied via a routine and well-known procedure, using a suturing technique. After implantation, the porous fibrous structure of ArtiFascia® provides a scaffold, which enables infiltration of fibroblasts and cells from the intact tissue, ultimately replacing damaged dural tissue. The patch is expected to resorb within a few months and to be replaced by the native tissue with complete dural closure. During the surgery and until patient's release from the hospital the patient's health will be closely monitored. Before the discharge patients will have to undergo neurological examination. Patients will be obligated to attend the follow up visits after the surgery at the dates scheduled by the attending physician. At each of the visits physical and neurological examinations will be performed. Radiographic Evaluation (Magnetic Resonance Imaging) will be performed also 6 months post operation. A total of 90 patients will be enrolled and implanted with test or control device. Up to 10 centers in Europe and Israel are planned to participate in this study. The primary endpoint will be achieved when the final study subject has completed a 6-months follow-up.

Official Title
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A Prospective, Randomized, Controlled Multi-center Study of ArtiFascia® Dural Repair Patch Compared With Commercially Available Dural Substitutes- NEOART Study.

Conditions
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Dural Tear, Cerebrospinal Fluid Leak

Intervention / Treatment
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* Device: Implantation of the ArtiFascia®
* Device: Implantation of other commercial suturable dural substitute


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject between the ages of 18-75 Subject is scheduled for an elective cranial surgery with a dural damage that can be completely repaired/closed by a suture-able dural substitute (ArtiFascia device or other commercially available dural substitutes) Subject has undergone radiographic imaging (such as, MRI) in the past 6 months before enrolment Surgical wound is expected to be Class I/clean Subject understands the study requirements and the treatment procedures and provides written Informed Consent before any study-specific tests or procedures are performed Subject is able and willing to adhere to the required follow-up visits and testing Exclusion Criteria: Pregnant women or interest in becoming pregnant during the duration of the study Subject has known hydrocephalus Subject is unable to undergo MRI after the surgery Subject's life expectancy is less than 12 months Subject has a local or systemic infection (e.g. urinary tract infection (UTI), active pneumonia) or evidence of any surgical site infection, fever > 38.3℃, positive blood culture and/or a positive chest x-ray for acute infectious process Subject will require use of dural adhesive or sealant Subject is intended to undergo craniectomy wherein bone flap will not be returned Subject with suspected low success in wound healing due to past treatments (e.g. chemotherapy, radiation therapy, severe diabetes etc.) or other conditions (e.g. severe peripheral vascular disease, long standing steroids treatment) Subject has been clinically diagnosed with malignancy (other than basal cell carcinoma or low-grade glioma), uncontrolled diabetes (A1C>6.5%), sepsis, systemic collagen disease. Subject had chemotherapy and/or radiotherapy in the past 12 weeks before surgery or is planned to have chemotherapy or radiotherapy less than 12 weeks after surgery. Subject is an acute cranial trauma surgical case Subjects with a concurrent disease that would place the patient in excessive risk to the planned surgery Subject had a previous neurosurgery in the same anatomical site Subject with other undesirable symptoms defined by the principal investigator Patient has clinically significant coagulopathy as determined by the surgeon Subject is participating in another clinical trial using similar investigational devices/drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm<br>Procedure will be performed under general anaesthesia. The patients will undergo a surgery that is identical to the one that was planned by the surgeon. At the end of the surgery, the investigator will use the ArtiFascia® patch. Implantation of the ArtiFascia® will be according to clinical discretion of the physician, and in compliance with ArtiFascia® instructions for use. Detailed instructions are in the instructions for use. Post operation the subject will stay at the hospital according to site standards and physician discretion. | Device: Implantation of the ArtiFascia®<br>* Following are the general instructions for use for the ArtiFascia®: Cut the ArtiFascia® to the required shape under aseptic conditions Apply ArtiFascia® to the damaged area Suture the ArtiFascia® in place Suture bites should be taken 2-3 millimeters from the edges of the implant. Either a running suture or interrupted stitches' technique may be used, depending on clinical conditions or surgeon's decision. Important Note: If clinically possible, do not use dural adhesive or sealants as it is an uncontrolled variable, that can influence the results.<br>|
| Active Comparator: Control<br>Same procedure as for the treatment arm but using a commercial suturable dural substitute. Implantation of the commercial suturable dural substitute will be according to clinical discretion of the physician, and in compliance with each specific device instructions for use. Detailed instructions are in the instructions for use. | Device: Implantation of other commercial suturable dural substitute<br>* Implantation of the commercial suturable dural substitute will be according to clinical discretion of the physician, and in compliance with each specific device instructions for use. Detailed instructions are in the instructions for use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and effectiveness of ArtiFascia® in comparison with commercially available suturable dural substitutes in subjects requiring Dural repair following neurosurgery | Safety and effectiveness will be assessed by evaluating the absence of CSF fistula (drainage from wound or sinus) and pseudo-meningocele post-operative as evaluated by MRI imaging. During MRI imaging CSF leakage will be assessed as: none/external leakage/subgaleal leakage. Additional if leakage is present, severity will be reported (mild/moderate/severe). | The rate of adverse events, adverse device effects and device deficiencies will be assessed on a continuous basis from the baseline (following signing the ICF) through the study completion at 6 month. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound healing assessment | Clean and/or fully healed vs. Infected. Evaluation of wound will be done in physical examination: clean and/or fully healed/ infected. If wound is infected additional assessment of mild/moderate/severe will be done. | 6 month follow-up | 
| Device Handling Characteristics | Based on scale to evaluate device: Suturing, seal quality, strength, ease of use (Score from 1=easy to 5=difficult). | 6 month follow-up | 
| Radiographic evaluation (Magnetic Resonance Imaging). | To determine the presence or absence of the following measure: adhesion formation, new tissue formation, pseudomeningocele, extracerebal fluid collection and brain edema adjacent to device implant size Measurements will be done based on MRI imaging (X,Y,Z axis; in milimeters). | 6 month follow-up |