Fibrin Sealant for the Sealing of Dura Sutures

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT00681824
First received: May 19, 2008
Last updated: May 21, 2013
Last verified: May 2013
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Incidence of Cerebrospinal Fluid (CSF) Leakage Observed After Surgery [ Time Frame: 33 +/- 3 days after surgery ] [ Designated as safety issue: No ]

    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 [ Time Frame: 33 +/- 3 days after surgery ] [ Designated as safety issue: No ]

    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:
  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: until resolution or 30 days after final follow-up visit (Day 33+/-3), whichever is first ] [ Designated as safety issue: No ]
    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 [ Time Frame: within 1 month following surgery ] [ Designated as safety issue: Yes ]
  • Number of Participants With Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria [ Time Frame: within 1 month following surgery ] [ Designated as safety issue: Yes ]

Enrollment: 95
Study Start Date: May 2008
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00681824

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

No publications provided

Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT00681824     History of Changes
Other Study ID Numbers: 550701
Study First Received: May 19, 2008
Results First Received: March 12, 2013
Last Updated: May 21, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
Pathologic Processes
Aprotinin
Fibrin Tissue Adhesive
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014