Cerebrospinal Fluid LeakPhase 3NCT02891070
Efficacy and Safety of FS VH S/D 500 S-apr (Tisseel) as an Adjunct to Sutured Dural Repair in Cranial Surgery
A Phase 3 study testing FS VH S/D 500 s-apr and DuraSeal Dural Sealant in people with Cerebrospinal Fluid Leak, run by Baxter Healthcare Corporation at 25 sites in 4 countries.
Trial summary
The objective of this study is to evaluate the safety and efficacy of FS VH S/D 500 s-apr for use as an adjunct to sutured dural repair in cranial surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebrospinal Fluid Leak
- What is being tested?
- FS VH S/D 500 s-apr and DuraSeal Dural Sealant
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 25 sitesin 4 countries
- Study dates
- 11 Oct 2016to 22 Aug 2018
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing craniotomy/craniectomy for pathological processes in the PF or ST region
- Patients must be willing and able to participate in the study and provide written IC before any protocol specific assessment is performed
- Patients must be willing to receive peri-operative antibiotic prophylaxis
- Female patients of childbearing potential must present with a negative serum pregnancy test, and must agree to employ adequate birth control measures [restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products] for the duration of their participation in the study
- Patients are willing and able to comply with the requirements of the protocol
Who cannot join
- Patients with a dural lesion from a recent surgery that still has the potential for CSF leakage
- Patients who had undergone chemotherapy treatment, excluding hormonal therapy, within 3 weeks prior to the planned procedure, or with chemotherapy scheduled within 7 days following surgery
- Patients with radiation therapy to the surgical site or standard fractionated radiation therapy scheduled within 7 days following surgery
- Patients with a previous craniotomy/craniectomy within 6 months prior to the study surgery
- Use of corticosteroids on a chronic basis (defined as daily use of corticosteroids for ≥8 weeks) for purposes other than decreasing the symptoms of systemic chemotherapy (unless if those steroids were discontinued 4 weeks prior to the planned surgery)
- Patients with a known hypersensitivity to the components of the IP or control (human fibrinogen, synthetic aprotinin, human albumin, human FXIII, tri sodium citrate, histidine, niacinamide, polysorbate 80, human thrombin, polyethylene glycol [PEG], trilysine amine)
Show all 20Show fewer
- Patients with a known hypersensitivity to US Federal Drug \& Cosmetic Blue #1 dye
- Evidence of an infection indicated by any one of the following: clinical examination supporting the diagnosis of infection, fever (temperature >100.7°F or 38.2°C), positive urine culture, positive blood culture, positive chest X ray consistent with pulmonary infection, or infection along the planned surgical path. A white blood cell (WBC) count of <20000 cells/µL is permitted if the patient is being treated with steroids in the absence of all other infection parameters
- Female patients of childbearing potential with a positive pregnancy test or intent to become pregnant during the clinical study period
- Female patients who are nursing
- Patients with exposure to another investigational drug or device clinical trial within 30 days prior to enrolment or anticipated in the 60-day Follow-up period
- Patients with severely altered renal function as confirmed by local laboratory reference ranges for serum creatinine and/or hepatic function (alanine aminotransferase [ALT], aspartate aminotransferase >3 × upper limit of normal [ULN])
- Patients who currently have or have had a compromised immune system (such as Acquired Immune Deficiency Syndrome [AIDS]) or autoimmune disease, or were on chronic immunosuppressant agents
- Patients with uncontrolled diabetes as evidenced by the institution's standard of care (glycated haemoglobin [HbA1c] >7%, blood glucose, etc.)
- Patients with traumatic injuries to the head
- Patients with dural injury during craniotomy/craniectomy that cannot be eliminated by widening the craniotomy/craniectomy to recreate the native dural cuff
- Patients requiring surgical approaches that would not allow sutured dural closure such as trans-sphenoidal or translabyrinthine/-petrosal/-mastoid. Superficial penetration of mastoid air cells is allowed
- Patients with hydrocephalus, except occlusive hydrocephalus caused by PF pathology or incompletely open cerebrospinal fluid pathways, to be treated during surgical procedure
- Existing CSF (ventricular, etc.) drains, Cushing/Dandy cannulation, or Burr holes which damage the dura
- Patients with confined bony structures where nerves are present and neural compression may result due to swelling
Trial locations and contacts
25 sites in 4 countries.
25 sites in 4 countries
United States10 sites
University of Virginia School of Medicine
Charlottesville, Virginia, 22903
University Hospitals Case Medical Center
Cleveland, Ohio, 44106
The Ohio State University
Columbus, Ohio, 43201
Henry Ford Hospital
Detroit, Michigan, 48202
Houston Methodist Neurological Institute
Houston, Texas, 77030
University of Minnesota
Minneapolis, Minnesota, 55455
Temple University School of Medicine
Philadelphia, Pennsylvania, 19140
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Baystate Medical Center
Springfield, Massachusetts, 01199
Czechia6 sites
University Hospital Brno
Brno, 62500
St. Anne's University Hospital Brno
Brno, 65691
University Hospital Hradec Kralove
Hradec Králové, 50005
University Hospital Ostrava
Ostrava, 70852
Hospital Na Homolce
Prague, 15030
University Hospital Motol
Praha 5 - Motol, 15006
Spain6 sites
University Hospital Germans Trias I Pujol
Badalona, 08916
Hospital Clinic I Provincial de Barcelona
Barcelona, 08036
University Hospital Foundation Jimenez Diaz
Madrid, 28040
University Hospital 12 de Octubre
Madrid, 28041
University Hospital Son Espases
Palma de Mallorca, 07010
University General Hospital of Valencia
Valencia, 46014
Germany3 sites
University Hospital Leipzig
Leipzig, 04103
Hospital Bogenhausen Municipal Hospital
Munich, 81925
University Hospital Rostock
Rostock, 18057
About this study
Official title: A Randomised Controlled Study to Evaluate the Efficacy and Safety of Fibrin Sealant, Vapour Heated, Solvent/Detergent Treated FS VH S/D 500 S-apr (Tisseel) Compared to DuraSeal Dural Sealant as an Adjunct to Sutured Dural Repair in Cranial Surgery.
The objective of this study is to evaluate the safety and efficacy of FS VH S/D 500 s-apr for use as an adjunct to sutured dural repair in cranial surgery.
- Conditions
- Cerebrospinal Fluid Leak
- Being tested
- FS VH S/D 500 s-apr, DuraSeal Dural Sealant
- Keywords
- Cranial Surgery, Cerebrospinal Fluid Leak, Tisseel
- Medical subject headings
- Cerebrospinal Fluid Leak
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FS VH S/D 500 s-aprDrug
Also called Tisseel
DuraSeal Dural SealantDevice
| Study group | Role | What they receive |
|---|---|---|
| FS VH S/D 500 s-apr | Experimental | FS VH S/D 500 s-apr (Tisseel), single use treatment, intraoperative Receives: Drug: FS VH S/D 500 s-apr |
| DuraSeal Dural Sealant | Active comparator | DuraSeal Dural Sealant, single use treatment, intraoperative Receives: Device: DuraSeal Dural Sealant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With No CSF Leak During and After Surgery
Participants who have no intra-operative CSF leak from dural repair after up to two applications during Valsalva maneuver (25 cm H2O for up to 5 - 10 seconds), or post-operative CSF leak within 30 (+3) days post-operatively. The Valsalva maneuver was performed by the anaesthesiologist to increase the intra-thoracic pressure (e.g., by increasing the positive end-expiratory pressure or by giving a large tidal volume and holding the inflating pressure) to approximately 25 cm H2O, constantly for up to 5 - 10 seconds to transiently elevate the intracranial pressure and test for any CSF leaks. The suture line was to be watertight after up to two product/control applications and Valsalva maneuvers.
Measured: Day 0 (Intra-operative) to Day 30 (+/-3 days) post-operative
Secondary outcomes (5)
Number of Participants With no Intra-operative CSF Leaks Following Final Valsalva Maneuver
Assessment of whether the suture line was not watertight causing CSF leaks after up to two product/control applications and Valsalva maneuvers.
Measured: Day 0 (Intra-operative)
Number of Participants With CSF Leaks Within 30 (+3) Days Post-operatively
Cerebrospinal fluid leak was defined as any overt flow, seepage, weeping, or sweating of CSF through the dura suture line, regardless of volume. All post-operative CSF leaks were primarily diagnosed based on a detailed history and physical examination, including neurological examination. Although not standard of care post-operatively, imaging tests such as computed tomography/magnetic resonance imaging (MRI) were considered if there was a high clinical suspicion of a CSF leak.
Measured: Day 0 (Intra-operative) to Day 30 (+/-3 days) post-operative
Duration in Surgery (Minutes)
Patients undergoing elective cranial surgery for the treatment of a pathological condition (e.g., benign/malignant tumours, vascular malformations, or Chiari type 1 malformations) specifically located in the posterior fossa (PF) or supratentorial (ST) regions.
Measured: Day 0 (intra-operatively)
Time From Dural Closure (Application of IP) Until End of Surgery
Suture closure techniques include continuous simple, continuous locked, interrupted.
Measured: Day 0 (Intra-operatively)
Length of Stay in Hospital (Days).
Days in hospital calculation is Day 0 - Discharge.
Measured: Day 0 to Day 60 (Study Completion)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2016 (estimated)
- Study start11 Oct 2016
- Primary completion22 Aug 2018
- Study completion22 Aug 2018
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 Cerebrospinal Fluid LeakStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxter Healthcare Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Qing Li, MD, PhD, Study director, Baxter Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02891070
- Sponsor's protocol ID
- 3599-001
- Other IDs
- 2015-005535-40, 2015
- Status last verified
- Aug 2019
- First submitted
- 1 Sep 2016
- Last updated
- 10 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Study to Evaluate the Efficacy and Safety of Fibrin Sealant, Vapour Heated, Solvent/Detergent Treated FS VH S/D 500 S-apr (Tisseel) Compared to DuraSeal Dural Sealant as an Adjunct to Sutured Dural Repair in Cranial Surgery.
- ClinicalTrials.gov ID
- NCT02891070
- Acronym / sponsor ID
- 3599-001
- Conditions
- Cerebrospinal Fluid Leak
- Keywords
- Cranial Surgery, Cerebrospinal Fluid Leak, Tisseel
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 224 participants (actual)
- Lead sponsor
- Baxter Healthcare CorporationIndustry (pharma, biotech, devices)
- Study start
- 11 Oct 2016 (actual)
- Primary completion
- 22 Aug 2018 (actual)
- Study completion
- 22 Aug 2018 (actual)
- First posted
- 7 Sep 2016 (estimated)
- Results
- Posted 10 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to evaluate the safety and efficacy of FS VH S/D 500 s-apr for use as an adjunct to sutured dural repair in cranial surgery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FS VH S/D 500 s-apr | Experimental | Drug: FS VH S/D 500 s-aprFS VH S/D 500 s-apr (Tisseel), single use treatment, intraoperative |
| DuraSeal Dural Sealant | Active comparator | Device: DuraSeal Dural SealantDuraSeal Dural Sealant, single use treatment, intraoperative |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients undergoing craniotomy/craniectomy for pathological processes in the PF or ST region
- Patients must be willing and able to participate in the study and provide written IC before any protocol specific assessment is performed
- Patients must be willing to receive peri-operative antibiotic prophylaxis
- Female patients of childbearing potential must present with a negative serum pregnancy test, and must agree to employ adequate birth control measures [restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products] for the duration of their participation in the study
- Patients are willing and able to comply with the requirements of the protocol
Key exclusion criteria (20 listed)
- Patients with a dural lesion from a recent surgery that still has the potential for CSF leakage
- Patients who had undergone chemotherapy treatment, excluding hormonal therapy, within 3 weeks prior to the planned procedure, or with chemotherapy scheduled within 7 days following surgery
- Patients with radiation therapy to the surgical site or standard fractionated radiation therapy scheduled within 7 days following surgery
- Patients with a previous craniotomy/craniectomy within 6 months prior to the study surgery
- Use of corticosteroids on a chronic basis (defined as daily use of corticosteroids for ≥8 weeks) for purposes other than decreasing the symptoms of systemic chemotherapy (unless if those steroids were discontinued 4 weeks prior to the planned surgery)
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 |
|---|---|---|
| FS VH S/D 500 s-aprAlso: Tisseel | Drug | FS VH S/D 500 s-apr |
| DuraSeal Dural Sealant | Device | DuraSeal Dural Sealant |
Primary outcome
Number of Participants With No CSF Leak During and After Surgery
Time frame: Day 0 (Intra-operative) to Day 30 (+/-3 days) post-operative
Participants who have no intra-operative CSF leak from dural repair after up to two applications during Valsalva maneuver (25 cm H2O for up to 5 - 10 seconds), or post-operative CSF leak within 30 (+3) days post-operatively. The Valsalva maneuver was performed by the anaesthesiologist to increase the intra-thoracic pressure (e.g., by increasing the positive end-expiratory pressure or by giving a large tidal volume and holding the inflating pressure) to approximately 25 cm H2O, constantly for up to 5 - 10 seconds to transiently elevate the intracranial pressure and test for any CSF leaks. The suture line was to be watertight after up to two product/control applications and Valsalva maneuvers.
5 secondary outcomes
Number of Participants With no Intra-operative CSF Leaks Following Final Valsalva Maneuver
Time frame: Day 0 (Intra-operative)
Number of Participants With CSF Leaks Within 30 (+3) Days Post-operatively
Time frame: Day 0 (Intra-operative) to Day 30 (+/-3 days) post-operative
Duration in Surgery (Minutes)
Time frame: Day 0 (intra-operatively)
Time From Dural Closure (Application of IP) Until End of Surgery
Time frame: Day 0 (Intra-operatively)
Length of Stay in Hospital (Days).
Time frame: Day 0 to Day 60 (Study Completion)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Cerebrospinal Fluid Leak
Not yet recruiting
A Prospective, Randomized, Two-Arm, Controlled, Single-Blind, Multi-Center Study to Evaluate the Safety and Efficacy of ArtiFix® Dural Repair Sealant Graft in Cranial and Spine Surgery (NEOFIX Study)
CerebroSpinal Fluid (CSF) Leak, Dural Tear
Recruiting
Role of Novel RADA16 Hydrogel in Endoscopic Skull Base Surgery
Skull Base Neoplasms, Cerebrospinal Fluid Leakage
RecruitingObservational study
Immiseal™ Dural Sealant Post-Market Registry Study
Dural Defect, Cerebrospinal Fluid Leak
Recruiting
Conservative vs Interventional Management of Postsurgical CSF Pseudomeningocele
CSF Leak, CSF Pressure Increased
Recruiting
Evaluation of Internal Nasal Splint-Supported Free Graft Versus Nasoseptal Flap for Endoscopic Skull Base Repair in Cerebrospinal Fluid Leaks
CSF Leak
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.
Qing Li, MD, PhD study director
Baxter Healthcare
25 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing FS VH S/D 500 s-apr and DuraSeal Dural Sealant in people with Cerebrospinal Fluid Leak, run by Baxter Healthcare Corporation at 25 sites in 4 countries.
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 5 inclusion and 20 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 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Czechia, Spain, Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 10 Sep 2019). 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?
Number of Participants With No CSF Leak During and After Surgery (time frame: Day 0 (Intra-operative) to Day 30 (+/-3 days) post-operative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Sep 2019.