Fibrin Sealant for the Sealing of Dura Sutures

Phase 2

Completed

Conditions: Pathological Processes in the Posterior Fossa
Dura Defects

Interventions: Biological: Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr)
Procedure: Standard of care

Registration Number: NCT00681824

Lead Sponsor: Baxter Healthcare Corporation

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 95

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FS VH S/D 500 s-apr	Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr)	Application of FS VH S/D 500 s-apr on top of suture
Standard of Care (Control group)	Standard of care	The treatment of the control group consisted of Standard of Care (SoC) which was defined as the closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen based dura substitute.

Primary Outcome Measures

Name	Time	Method
Incidence of Cerebrospinal Fluid (CSF) Leakage Observed After Surgery	33 +/- 3 days after surgery	Study-relevant CSF leakage is defined as one or more of following: 1. Discrete subcutaneous or subgaleal CSF collection (pseudomeningocele) in surgical area confirmed by positive test for β2-transferrin, or by computed tomography (CT) or magnetic resonance imaging (MRI) 2. Epidural CSF collection in surgical area depicted by CT or MRI 3. Leakage of CSF through surgical wound observed during physical examination, confirmed by a positive test for β2-transferrin 4. Progressive pneumatocephalus (air in subarachnoidal space) depicted by repeat CT in absence of CSF drainage.
Number of Participants With Cerebrospinal Fluid (CSF) Leakage Observed After Surgery	33 +/- 3 days after surgery	Study-relevant CSF leakage is defined as one or more of following: 1. Discrete subcutaneous or subgaleal CSF collection (pseudomeningocele) in surgical area confirmed by positive test for β2-transferrin, or by computed tomography (CT) or magnetic resonance imaging (MRI) 2. Epidural CSF collection in surgical area depicted by CT or MRI 3. Leakage of CSF through surgical wound observed during physical examination, confirmed by a positive test for β2-transferrin 4. Progressive pneumatocephalus (air in subarachnoidal space) depicted by repeat CT in absence of CSF drainage.

Secondary Outcome Measures

Name	Time	Method
Incidence of Procedures Resulting From the Treatment of CSF Leaks	until resolution or 30 days after final follow-up visit (Day 33+/-3), whichever is first	The incidence of surgical revisions, number and duration of compression bandage applications and of liquor drainage procedures
Number of Participants With Procedures Resulting From the Treatment of CSF Leaks	until resolution or 30 days after final follow-up visit (Day 33+/-3), whichever is first	The number of participants with surgical revisions, number and duration of compression bandage applications and of liquor drainage procedures.
Incidence of Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria	within 1 month following surgery
Number of Participants With Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria	within 1 month following surgery