Fibrin Sealant for the Sealing of Dura Sutures

NCT00681824 | Completed Phase 2 Results

• 1 other identifier: 550701
• Study Type: interventional
• Target: 95
• Locations: 2 countries
• Sites: 13

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.

Conditions

Pathological Processes in the Posterior Fossa; Dura Defects

Outcome Measures

Primary Outcomes (2)

• Incidence of Cerebrospinal Fluid (CSF) Leakage Observed 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.

  33 +/- 3 days after surgery

• Number of Participants With Cerebrospinal Fluid (CSF) Leakage Observed 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.

  33 +/- 3 days after surgery

Secondary Outcomes (4)

• 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

• 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

• 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

Study Arms (2)

FS VH S/D 500 s-apr

EXPERIMENTAL

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)

Standard of Care (Control group)

ACTIVE COMPARATOR

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

Interventions

Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) BIOLOGICAL

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.

Also known as: TISSEEL, FS VH S/D 500 s-apr (a double virus-inactivated biological two-component fibrin sealant)

FS VH S/D 500 s-apr

Standard of care PROCEDURE

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.

Standard of Care (Control group)

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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 \[ALT, AST \> 5 x upper limit of norm (ULN)\]
• 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
• Dura injury during craniotomy / craniectomy that cannot be eliminated by recreating a sufficiently wide native dura hem
• Failure to administer preoperative antibiotic prophylaxis

Sponsors & Collaborators

• Baxter Healthcare Corporation: lead

Study Sites (13)

Unknown Facility

Duarte, California, United States

Location

Unknown Facility

Sacramento, California, United States

Location

Unknown Facility

San Diego, California, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Louisville, Kentucky, United States

Location

Unknown Facility

Johnson City, New York, United States

Location

Unknown Facility

Winston-Salem, North Carolina, United States

Location

Unknown Facility

Columbus, Ohio, United States

Location

Unknown Facility

Hershey, Pennsylvania, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Hamilton, Ontario, Canada

Location

MeSH Terms

Interventions

Fibrin Tissue Adhesive; Solvents; Thrombin; Low Density Lipoprotein Receptor-Related Protein-1; Standard of Care

Intervention Hierarchy (Ancestors)

Fibrin; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Specialty Uses of Chemicals; Chemical Actions and Uses; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Blood Coagulation Factors; Biological Factors; LDL-Receptor Related Proteins; Receptors, LDL; Receptors, Lipoprotein; Receptors, Cell Surface; Membrane Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Guenter Zuelow, Associate Medical Director
• Organization: Baxter Healthcare Corporation

guenter_zuelow@baxter.com

Study Officials

• Guenter Zuelow, MD

  Baxter Healthcare Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2008
• First Posted: May 21, 2008
• Study Start: May 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: June 27, 2013
• Results First Posted: June 27, 2013

Record last verified: 2013-05

Locations

US (12); CA (1)