Pathological Processes in the Posterior FossaPhase 2NCT00681824

Fibrin Sealant for the Sealing of Dura Sutures

A Phase 2 study testing Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) in people with Pathological Processes in the Posterior Fossa and Dura Defects, run by Baxter Healthcare Corporation at 13 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 3 years and older
Conditions the study is for: Pathological Processes in the Posterior Fossa, Dura Defects
What is being tested?: Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr)
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 95 participants
Where: 13 sitesin 2 countries
Study dates: May 2008to Mar 2010
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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)]

Show all 29Show fewer

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

Trial locations and contacts

13 sites in 2 countries.

Country

City, postcode or hospital

13 sites in 2 countries

United States12 sites

Study site
Atlanta, Georgia
Study site
Chicago, Illinois
Study site
Columbus, Ohio
Study site
Duarte, California
Study site
Hershey, Pennsylvania
Study site
Johnson City, New York
Study site
Louisville, Kentucky
Study site
Orlando, Florida
Study site
Philadelphia, Pennsylvania
Study site
Sacramento, California
Study site
San Diego, California
Study site
Winston-Salem, North Carolina

Other trials in United States

Canada1 site

Study site
Hamilton, Ontario

Other trials in Canada

About this study

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

Conditions: Pathological Processes in the Posterior Fossa, Dura Defects
Being tested: 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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr)Biological
Also called TISSEEL, FS VH S/D 500 s-apr (a double virus-inactivated biological two-component fibrin sealant)
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 of careProcedure or surgery
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.

Study groups in NCT00681824
Study group	Role	What they receive
FS VH S/D 500 s-apr	Experimental	Application of FS VH S/D 500 s-apr on top of suture Receives: 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. Receives: Procedure: Standard of care

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 33 +/- 3 days after surgery

Secondary outcomes (4)

Incidence of Procedures Resulting From the Treatment of CSF Leaks
The incidence of surgical revisions, number and duration of compression bandage applications and of liquor drainage procedures
Measured: 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
The number of participants with surgical revisions, number and duration of compression bandage applications and of liquor drainage procedures.
Measured: 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
Measured: within 1 month following surgery
Number of Participants With Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria
Measured: within 1 month following surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2008Mar 2010

First posted21 May 2008 (estimated)
Study startMay 2008
Primary completionMar 2010
Study completionMar 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pathological Processes in the Posterior FossaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 95 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00681824
Sponsor's protocol ID: 550701
Status last verified: May 2013
First submitted: 19 May 2008
Last updated: 27 Jun 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 27 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00681824
Acronym / sponsor ID: 550701
Conditions: Pathological Processes in the Posterior Fossa, Dura Defects
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 95 participants (actual)
Lead sponsor: Baxter Healthcare CorporationIndustry (pharma, biotech, devices)
Study start: May 2008
Primary completion: Mar 2010 (actual)
Study completion: Mar 2010 (actual)
First posted: 21 May 2008 (estimated)
Results: Posted 27 Jun 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
FS VH S/D 500 s-apr	Experimental	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 FS VH S/D 500 s-apr on top of suture
Standard of Care (Control group)	Active comparator	Procedure: Standard of careThe 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.

Who may qualify

Ages: 3 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

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.

Key exclusion criteria (29 listed)

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)]

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr)Also: TISSEEL, FS VH S/D 500 s-apr (a double virus-inactivated biological two-component fibrin sealant)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.	Biological	FS VH S/D 500 s-apr
Standard of careStandard care: defined as the closure of a dura defect by suturing in a patch of autologous fascia, pericranium or suturable collagen-based dura substitute.	Procedure or surgery	Standard of Care (Control group)

Primary outcome

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.
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.

4 secondary outcomes

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
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
Incidence of Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria
Time frame: within 1 month following surgery
Number of Participants With Surgical Site Infections (SSI) According to National Nosocomial Infection Surveillance (NNIS) Criteria
Time frame: within 1 month following surgery

Results and safety

Results posted to the registry on 27 Jun 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Standard of Care	28	27
Run-in Participants: FS VH S/D 500 S-apr	13	12
FS VH S/D 500 S-apr	34	33

Primary outcome: Incidence of Cerebrospinal Fluid (CSF) Leakage Observed After Surgery

Time frame: 33 +/- 3 days after surgery. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Standard of Care (SoC) n = 27	FS VH S/D 500 S-apr n = 32
Value	74.07 (55.32 to 86.83)	78.13 (61.25 to 88.98)

Standard of Care (SoC) vs FS VH S/D 500 S-apr: p = 0.7159, likelihood ratio of chi squared test

Population analysed: Intent to treat One participant (SoC arm) received products other than FS VH S/D 500 s-apr for sealing of dura sutures and was removed from analysis Two participants (FS VH S/D 500 s-apr arm) removed from analysis due to (1) subsequent surgery unrelated to CSF leakage/surgical site infection that involved re-durotomy (2) withdrew from study

Primary outcome: Number of Participants With Cerebrospinal Fluid (CSF) Leakage Observed After Surgery

Time frame: 33 +/- 3 days after surgery. Number. Unit: participants

Measure	Standard of Care (SoC) n = 27	FS VH S/D 500 S-apr n = 32
Value	20	25

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Throughout the study period, 1 year and 10 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Standard of Care (SoC)	4 of 28 (14.3%)	20 of 28 (71.4%)	Not reported
FS VH S/D 500 S-apr	10 of 47 (21.3%)	33 of 47 (70.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Guenter Zuelow, MD study director

Baxter Healthcare Corporation

13 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Cerebrospinal Fluid (CSF) Leakage Observed After Surgery (time frame: 33 +/- 3 days after surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00681824.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2013.