Fibrin Sealant for the Sealing of Dura Sutures

• ClinicalTrials.gov Identifier: NCT00681824
• Recruitment Status: Completed
• First Posted: May 21, 2008
• Results First Posted: June 27, 2013
• Last Update Posted: June 27, 2013
• Sponsor: Baxter Healthcare Corporation
• Information provided by (Responsible Party): Baxter Healthcare Corporation

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pathological Processes in the Posterior Fossa; Dura Defects	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	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Exploratory Phase 2 Study Evaluating the Efficacy and Safety of Fibrin Sealant, Vapor Heated, Solvent/Detergent Treated (FS VH S/D) 500 S-APR for the Sealing of Dura Defect Sutures in Posterior Fossa Surgery
• Study Start Date: May 2008
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: March 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: FS VH S/D 500 s-apr; Application of FS VH S/D 500 s-apr on top of suture	Biological: Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr); 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.; Other Names: TISSEEL; FS VH S/D 500 s-apr (a double virus-inactivated biological two-component fibrin sealant)
Active Comparator: Standard of Care (Control group); 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.	Procedure: Standard of care; 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.

Outcome Measures

Primary Outcome Measures :

1. Incidence of Cerebrospinal Fluid (CSF) Leakage Observed After Surgery [ Time Frame: 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.
2. Number of Participants With Cerebrospinal Fluid (CSF) Leakage Observed After Surgery [ Time Frame: 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 :

1. Incidence of Procedures Resulting From the Treatment of CSF Leaks [ Time Frame: 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
2. Number of Participants With Procedures Resulting From the Treatment of CSF Leaks [ Time Frame: 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.
3. Incidence of Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria [ Time Frame: within 1 month following surgery ]
4. Number of Participants With Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria [ Time Frame: within 1 month following surgery ]

Eligibility Criteria

• Ages Eligible for Study: 3 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Duarte, California, United States

Sacramento, California, United States

San Diego, California, United States

United States, Florida

Orlando, Florida, United States

United States, Georgia

Atlanta, Georgia, United States

United States, Illinois

Chicago, Illinois, United States

United States, Kentucky

Louisville, Kentucky, United States

United States, New York

Johnson City, New York, United States

United States, North Carolina

Winston-Salem, North Carolina, United States

United States, Ohio

Columbus, Ohio, United States

United States, Pennsylvania

Hershey, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Canada, Ontario

Hamilton, Ontario, Canada

Sponsors and Collaborators

Baxter Healthcare Corporation

Investigators

• Study Director: Guenter Zuelow, MD; Baxter Healthcare Corporation

More Information

• Responsible Party: Baxter Healthcare Corporation
• ClinicalTrials.gov Identifier: NCT00681824
• Other Study ID Numbers: 550701
• First Posted: May 21, 2008
• Results First Posted: June 27, 2013
• Last Update Posted: June 27, 2013
• Last Verified: May 2013

Additional relevant MeSH terms:

Pathologic Processes; Fibrin Tissue Adhesive; Thrombin; Aprotinin; Hemostatics; Coagulants; Trypsin Inhibitors; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action