Cerebrospinal Fluid Leak, Dural Tear
Conditions
Brief summary
The objective of this study was to evaluate the safety and effectiveness of ArtiFascia® in comparison with commercially available dural substitutes in subjects requiring Dural repair following neurosurgery. Subjects with planned cranial neurosurgery participated in this study. During the surgery the 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. The damaged dura can be fixed with dural patch like ArtiFascia®. ArtiFascia® is a bioabsorbable medical synthetic dural replacement that aids in the regeneration of a new dura. Furthermore, it incorporates a sealing layer capable of minimizing CSF leakage and infection.
Detailed description
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 polymeric synthetic dural substitute that is absorbed by the body. Before the study, all subjects underwent neurological assessment. Only subjects that were found to be suitable to participate in the study, and agree to participate, were randomly allocated into one of the following groups: * Experimental group (ArtiFascia® device); * Control group (Other commercially available suturable dural substitutes). The Sponsor was blinded to treatment. The subjects underwent the planned surgery and at the end the investigator used ArtiFascia® patch or standard dural substitute to repair the damaged Dura. ArtiFascia® graft was placed in areas where the native dural layer was damaged or missing. ArtiFascia® was 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 subject's release from the hospital the subject's health was closely monitored. Before the discharge subjects underwent neurological examination. Subjects had been followed up at 4-6 weeks and at 6 months post surgery. At each follow up visit physical and neurological examinations were performed. Radiographic Evaluation (Magnetic Resonance Imaging) was performed at 6 months post operation. A total of 92 subjects from 7 sites in Europe were enrolled and implanted with test or control device. The primary endpoint was achieved when the final study subject has completed a 6-months follow-up.
Interventions
DEVICEImplantation of the ArtiFascia®
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.
DEVICEImplantation of other 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
Sponsors
Nurami Medical Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subject between the ages of 18-75 2. 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) 3. Subject has undergone radiographic imaging (such as, MRI) in the past 6 months before enrolment 4. Surgical wound is expected to be Class I/clean 5. Subject understands the study requirements and the treatment procedures and provides written Informed Consent before any study-specific tests or procedures are performed 6. Subject is able and willing to adhere to the required follow-up visits and testing
Exclusion criteria
1. Pregnant women or interest in becoming pregnant during the duration of the study 2. Subject has known hydrocephalus 3. Subject is unable to undergo MRI after the surgery 4. Subject's life expectancy is less than 12 months 5. 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 6. Subject will require use of dural adhesive or sealant 7. Subject is intended to undergo craniectomy wherein bone flap will not be returned 8. 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) 9. 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. 10. 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. 11. Subject is an acute cranial trauma surgical case 12. Subjects with a concurrent disease that would place the patient in excessive risk to the planned surgery 13. Subject had a previous neurosurgery in the same anatomical site 14. Subject with other undesirable symptoms defined by the principal investigator 15. Patient has clinically significant coagulopathy as determined by the surgeon 16. Subject is participating in another clinical trial using similar investigational devices/drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absence of Cerebrospinal Fluid Fistula (Drainage From Wound or Sinus) and Pseudo-meningocele Within 6 Months Post-operative as Evaluated by MRI Imaging. | 6 month. | The primary end point will be assessed by evaluating the absence of cerebrospinal fluid fistula (drainage from wound or sinus) and pseudo-meningocele post-operative as evaluated by MRI imaging and physical examination of the surgical site. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wound Healing Assessment | 6 month follow-up | 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. |
| Device Handling Characteristics as Reported by a User Experience Questionnaire | On the day of the surgical procedure | The following scoring system was used for the evaluation: 1\) Device ease of use, suturing and cutting were evaluated on a scale of 1=Easy to 5=Difficult. 2) Device strength and seal quality (during implantation) were scored on scale of 1=Low to 5=High. |
| Radiological Imaging at 6 Months for Additional Findings at Implant Site | 6 month follow-up | The rate of each of the following: Extracerebral fluid accumulation, pseudomeningocele, adhesion formation, brain edema adjacent to device implant site, abnormal thickening at implantation site and new membrane (scar) formation. |
Countries
Belgium, Czechia, Israel, Poland, Spain
Participant flow
Recruitment details
The clinical trial was performed in 8 European medical centers (Poland, Czech Republic, Spain and Belgium) and in 1 Israeli medical center. Subjects were enrolled from January 2020 to January 2022.
Pre-assignment details
A total of 92 subjects met the inclusion/exclusion criteria, were randomized and enrolled. Of those 92 subjects, 89 received surgical treatment. Of those 89 treated subjects, 85 completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm-ArtiFascia® Graft The treatment arm consists of patients implanted with ArtiFascia® graft following cranial surgery. | 63 |
| Control-Other Commercial Suturable Dural Substitute The control arm consists of patients implanted with other commercial suturable dural substitute, including: Neuro-patch, ReDura, Tachosil, Tutopatch and Duragen. | 29 |
| Total | 92 |
Baseline characteristics
| Characteristic | Treatment Arm-ArtiFascia® Graft | Total | Control-Other Commercial Suturable Dural Substitute |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 15 Participants | 20 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 71 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 18 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 74 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 62 Participants | 91 Participants | 29 Participants |
| Region of Enrollment Belgium | 3 participants | 5 participants | 2 participants |
| Region of Enrollment Czechia | 19 participants | 28 participants | 9 participants |
| Region of Enrollment Poland | 28 participants | 40 participants | 12 participants |
| Region of Enrollment Spain | 13 participants | 19 participants | 6 participants |
| Sex: Female, Male Female | 43 Participants | 64 Participants | 21 Participants |
| Sex: Female, Male Male | 20 Participants | 28 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 63 | 0 / 29 |
| other Total, other adverse events | 26 / 63 | 15 / 29 |
| serious Total, serious adverse events | 9 / 63 | 3 / 29 |
Outcome results
Primary
Absence of Cerebrospinal Fluid Fistula (Drainage From Wound or Sinus) and Pseudo-meningocele Within 6 Months Post-operative as Evaluated by MRI Imaging.
The primary end point will be assessed by evaluating the absence of cerebrospinal fluid fistula (drainage from wound or sinus) and pseudo-meningocele post-operative as evaluated by MRI imaging and physical examination of the surgical site.
Time frame: 6 month.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control-Other Commercial Suturable Dural Substitute | Absence of Cerebrospinal Fluid Fistula (Drainage From Wound or Sinus) and Pseudo-meningocele Within 6 Months Post-operative as Evaluated by MRI Imaging. | Presence of cerebrospinal fluid fistula and Pseudomeningocele | 0 Participants |
| Control-Other Commercial Suturable Dural Substitute | Absence of Cerebrospinal Fluid Fistula (Drainage From Wound or Sinus) and Pseudo-meningocele Within 6 Months Post-operative as Evaluated by MRI Imaging. | No events of cerebrospinal fluid fistula and Pseudomeningocele | 27 Participants |
| Treatment Arm-ArtiFascia® Graft | Absence of Cerebrospinal Fluid Fistula (Drainage From Wound or Sinus) and Pseudo-meningocele Within 6 Months Post-operative as Evaluated by MRI Imaging. | No events of cerebrospinal fluid fistula and Pseudomeningocele | 58 Participants |
| Treatment Arm-ArtiFascia® Graft | Absence of Cerebrospinal Fluid Fistula (Drainage From Wound or Sinus) and Pseudo-meningocele Within 6 Months Post-operative as Evaluated by MRI Imaging. | Presence of cerebrospinal fluid fistula and Pseudomeningocele | 0 Participants |
Secondary
Device Handling Characteristics as Reported by a User Experience Questionnaire
The following scoring system was used for the evaluation: 1\) Device ease of use, suturing and cutting were evaluated on a scale of 1=Easy to 5=Difficult. 2) Device strength and seal quality (during implantation) were scored on scale of 1=Low to 5=High.
Time frame: On the day of the surgical procedure
Secondary
Radiological Imaging at 6 Months for Additional Findings at Implant Site
The rate of each of the following: Extracerebral fluid accumulation, pseudomeningocele, adhesion formation, brain edema adjacent to device implant site, abnormal thickening at implantation site and new membrane (scar) formation.
Time frame: 6 month follow-up
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control-Other Commercial Suturable Dural Substitute | Radiological Imaging at 6 Months for Additional Findings at Implant Site | Present measures | 1 Participants |
| Control-Other Commercial Suturable Dural Substitute | Radiological Imaging at 6 Months for Additional Findings at Implant Site | No findings presence | 57 Participants |
| Treatment Arm-ArtiFascia® Graft | Radiological Imaging at 6 Months for Additional Findings at Implant Site | Present measures | 3 Participants |
| Treatment Arm-ArtiFascia® Graft | Radiological Imaging at 6 Months for Additional Findings at Implant Site | No findings presence | 24 Participants |
Secondary
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.
Time frame: 6 month follow-up