Bioseal Dural Sealing Study BIOS-14-001

Study Overview
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Brief Summary
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A Prospective, Randomized, Controlled, Single Blinded, Study to Evaluate the Safety and Effectiveness of Bioseal as an Adjunct to Sutured Dural Repair

Detailed Description
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This is a randomized, single blinded, multi-center controlled study evaluating the effectiveness of Bioseal as an adjunct to sutured dural closure compared to control to obtain an intra-operative watertight dural closure.

Official Title
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A Prospective, Randomized, Controlled, Single Blinded, Study to Evaluate the Safety and Effectiveness of Bioseal as an Adjunct to Sutured Dural Repair

Conditions
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Benign Tumors, Malignant Tumors, Vascular Malformation

Intervention / Treatment
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* Biological: Bioseal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preoperative Patient undergoing elective craniotomy/craniectomy for pathological processes (such as benign and malignant tumors, vascular malformation) in the posterior fossa or in the supratentorial region. Age ≥ 18 years. Patients who are able and willing to comply with the procedures required by the protocol. Signed and dated written informed consent from the subject or from his/her legal representative prior to any study-specific procedures. Intraoperative Patient undergoing elective craniotomy/craniectomy for pathological processes (such as benign and malignant tumors, vascular malformation) in the posterior fossa or in the supratentorial region and who are demonstrated to have persistent CSF leakage following suture closure of the dural incision. CSF leakage will be evaluated during a period of Valsalva of 10-20 cm of H20 for 5-10 seconds. If a spontaneous leak is apparent immediately after dural closure, no Valsalva will be performed. Surgical wound classification Class I. Penetration of mastoid air cells during partial mastoidectomy is permitted. The cuff of native dura along the craniotomy edge is ≥10 mm wide, to facilitate suturing and to allow for sufficient surface area for adherence of the investigational product. Exclusion Criteria: Preoperative Subjects with a dura lesion from a recent surgery that still has the potential for CSF leakage. The previous craniotomy/ craniectomy within 6 months or radiation therapy within 2 years before this surgery. Chemotherapy or radiation therapy scheduled within 7 days following surgery. Subjects with severely altered renal (serum creatinine >2 mg/dL) and/or hepatic function [ALT, AST > 5 x upper limit of norm (ULN)]. Severe Anemia (Hemoglobin <60 g/L) or Hypoproteinemia (Total protein <60 g/L or 6g% ) . Non-compliant or insufficient treatment of diabetes mellitus [glycosylated hemoglobin (HbA1c) > 7.5%]. Conditions compromising the immune system; existence of autoimmune disease. Evidence of a potential infection: fever >38℃, WBC <3500/uL or >13000/uL, positive urine culture, positive blood culture, positive chest X-ray, evidence of infection along the planned surgical path. Known hypersensitivity to the porcine fibrin sealant product. Female subjects of childbearing potential with a positive urine or serum pregnancy test within 7 days prior to surgery. Female subjects who are breastfeeding or intend to become pregnant during the clinical study period. Participation in another clinical trial with exposure to another investigational drug or device within 30 days prior to enrolment. Intraoperative Native dura cuff during craniotomy/craniectomy that cannot be completely repaired. Use of implants made of synthetic materials coming into direct contact with dura (e.g., PTFE patches, shunts, ventricular and subdural drains). Occlusive hydrocephalus caused by posterior fossa pathology or partial blockage of CSF pathways during surgical procedure. Existing CSF drains on the surgical path. Use of other fibrin sealants for hemostasis. Placement of Gliadel Wafers or similar products. Persistently increased brain surface tension that may lead to an incomplete repair requiring. Intersecting durotomy scars in the surgical path from a previous operation that cannot be completely removed by the planned dura resection. Two or more separate dura defects during surgery. Others in addition to above exclusion criteria, the subject, in the opinion of the investigator, would not be suitable for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| No Intervention: suture (control)<br>Subjects randomized to control will receive additional dural sutures as deemed necessary by the surgeon. CSF leakage will be re-evaluated with the Valsalva maneuver to 10-20 cm H2O for 5 to 10 seconds. Closure of the remaining layers of the surgical site will be performed according to the surgeon's standard of practice. | |
| Experimental: Bioseal<br>Subjects randomized to receive Bioseal, a thin layer will be applied to the entire length of the suture line and the adjacent area to approximately 5mm away, including all suture holes. Up to two layers of Bioseal may be used for each application. While Bioseal achieves complete coagulation, CSF leakage will be re-evaluated with the Valsalva maneuver to 10-20 cm H2O for 5 to 10 seconds. Up to two applications (one application includes applying up to two layers of Bioseal product followed by the CSF leakage re-evaluation with Valsalva maneuver) per subject are allowed. Closure of the remaining layers of the surgical site will be performed according to the surgeon's standard of practice. | Biological: Bioseal<br>* Upon completion of the sutured dural repair, the closure will be evaluated for intra-operative CSF leakage with a baseline Valsalva maneuver to 10-20 cm H2O for 5-10 seconds. Subjects who have a CSF leak will be enrolled into the study. If randomized to receive Bioseal, a thin layer will be applied to the entire length of the suture line and the adjacent area to approximately 5mm away, including all suture holes. Up to two layers of Bioseal may be used for each application. While Bioseal achieves complete coagulation, CSF leakage will be re-evaluated with the Valsalva maneuver to 10-20 cm H2O for 5 to 10 seconds.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of success (watertight closure) CSF leakage | no CSF leakage from dural repair intra-operatively | 5 to 10 seconds after final Valsalva maneuver | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of CSF leakage | Incidence of CSF leakage post-surgery to discharge | Up to Discharge, an average of 3-5days in general | 
| Incidence of CSF leakage | Incidence of CSF leakage 30 (±7) days post operatively | Up to 30(+/-7)Days | 
| Incidence of adverse events | Incidence of adverse events | Up to 30(±7)Days | 
| Incidence of surgical site infections (SSI) | Incidence of surgical site infections (SSI) according to Surgical Site Infection Infection Prevention and Control Guideline (MOH) criteria | Up to 30(± 7) days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioseal as an Adjunct to Sutured Dural Repair, elective posterior fossa, supratentorial procedure