Fibrin Sealant for the Sealing of Dura Sutures
Condition: Pathological Processes in the Posterior Fossa; Dura Defects
MeSH terms: Pathologic Processes
Intervention: Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr); Standard of care
Intervention description: Application of a thin layer of FS VH S/D 500 s-apr to the entire length of the suture loop and the adjacent area to at least 5 mm away from the suture line, including all suture holes. After application, the product is to be allowed to polymerize for 3 minutes.; Standard care: defined as the closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.
Intervention MeSH terms: Thrombin; Fibrin Tissue Adhesive; Aprotinin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 95.0
Sex: All
Minimum age: 3 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to investigate the efficacy and safety of FS VH S/D 500 s-apr, a
      double virus-inactivated biological two-component fibrin sealant, for use in posterior fossa
      surgery as an adjunct to dura and dura substitute sutures in preventing postoperative
      cerebrospinal fluid (CSF) leakage.
    

Eligibility criteria:

        Inclusion Criteria:

        Preoperative Inclusion Criteria:

          -  Subjects undergoing elective craniotomy / craniectomy for pathological processes in
             the posterior fossa (such as benign and malignant tumors, vascular malformations, and
             Chiari 1 malformations) that result in dura defects requiring dura substitution for
             closure and 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-related procedures

          -  Age >= 3 years, either gender

        Intraoperative Inclusion Criteria:

          -  Surgical Wound Classification Class I and Risk Index Category (RIC) <= 2. Penetration
             of mastoid air cells during partial mastoidectomy is permitted and will be recorded.

          -  A patch of autologous fascia or pericranium or suturable collagen-based dura
             substitute was cut to size and then sutured into the dura defect.

          -  The hem of native dura exposed along and under the craniotomy edge is wide enough to
             facilitate suturing and to allow for sufficient surface area for adherence of the
             investigational product.

        Exclusion Criteria:

        Preoperative Exclusion Criteria:

          -  Female subjects who are breastfeeding, pregnant, or intend to become pregnant during
             the clinical study period

          -  Subjects with a dura lesion from a recent surgery that still has the potential for
             cerebrospinal fluid (CSF) leakage unless it can be expected that the lesion will be
             excised completely, including all old suture holes

          -  Chemotherapy scheduled within 7 days following surgery

          -  Radiation therapy to the head 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)]

          -  Evidence of an infection indicated by any one of the following: fever > 101°F, white
             blood cell (WBC) count < 3500/μL or > 13000/μL, positive blood culture, positive chest
             X-ray. A positive urine culture (> 10^5 colony-forming units (CFU)/mL) leads to
             exclusion unless acute cystitis is the sole cause. Evidence of infection along the
             planned surgical path. A WBC count of < 20000/μL is permitted if the patient is being
             treated with steroids in the absence of all the other infection parameters.

          -  Conditions compromising the immune system; existence of autoimmune disease

          -  Known hypersensitivity to aprotinin or other components of the investigational product

          -  Non-compliant or insufficient treatment of diabetes mellitus [glycosylated hemoglobin
             (HbA1c) > 7.5%]

          -  Hydrocephalus, except occlusive hydrocephalus caused by posterior fossa pathology to
             be treated

          -  Existing CSF (ventricular, etc.) drains. Burr holes are permitted as long as the dura
             remains intact. Cushing cannulation excludes the subject.

          -  Female subjects of childbearing potential with a positive urine or serum pregnancy
             test within 24 hours prior to surgery

          -  Participation in another clinical trial with exposure to another investigational drug
             or device within 30 days prior to enrollment

          -  Scheduled or foreseeable surgery within the follow-up period

        Intraoperative Exclusion Criteria:

          -  Dura injury during craniotomy / craniectomy that cannot be eliminated by recreating a
             sufficiently wide native dura hem

          -  Failure to administer preoperative antibiotic prophylaxis

          -  Use of implants made of synthetic materials coming into direct contact with dura
             (e.g., polytetrafluoroethylene (PTFE) patches, shunts, ventricular and subdural
             drains)

          -  Placement of Gliadel wafers

          -  Chiari 1 subjects without injury to the arachnoid

          -  Persistent signs of increased brain turgor

          -  Use of product(s) other than FS VH S/D 500 s-apr for the sealing of dura sutures,
             including packing with Gelfoam

          -  Brain surface visible between suture loops as a manifestation of increased suture
             tension

          -  CSF leakage from completed dura sutures presenting as dripping drops, growing beads or
             running trickles. Slight oozing is consistent with successful dura repair and will not
             lead to exclusion.

          -  Intersecting durotomy scars in the surgical path from a previous operation that cannot
             be completely removed by the planned dura resection

          -  Dura lesion from a recent surgery that cannot be completely excised, including all old
             suture holes

          -  Two or more separate dura defects

          -  Major intraoperative complications that require resuscitation or deviation from the
             planned surgical procedure