Cerebrospinal Fluid LeakPhase 3NCT02457546
The EVICEL® Neurosurgery Phase III Study
A Phase 3 study testing EVICEL Fibrin Sealant and Hydrogel sealant in people with Cerebrospinal Fluid Leak, run by Ethicon, Inc. at 26 sites in 6 countries.
Trial summary
The objective of this study is to evaluate the safety and efficacy of EVICEL® Fibrin Sealant (Human) 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?
- EVICEL Fibrin Sealant and Hydrogel sealant
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 234 participants
- Where
- 26 sitesin 6 countries
- Study dates
- 1 Jul 2015to 12 Oct 2017
- 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
- Subjects ≥18 years of age undergoing craniotomy/craniectomy for pathological processes in the supratentorial region or posterior fossa
- Subjects or legally authorized representatives must be willing to participate in the study and provide written informed consent.
- Surgical wound classification Class I
- The cuff of native dura along the craniotomy edge on each side is adequate, based on surgeon's judgment, to facilitate suturing and to allow for sufficient surface area for adherence of the investigational product
- Presence of intra-operative cerebrospinal fluid (CSF) leakage following primary dural closure or after Valsalva maneuver
Who cannot join
- Subjects with a dural lesion from a recent surgery that still has the potential for CSF leakage.
- Chemotherapy within 30-days prior to enrollment or scheduled within 7-days following surgery
- Radiation therapy to the head within 30-days prior to enrollment or scheduled within 7-days following surgery
- A previous craniotomy/craniectomy within 6 months prior to the study surgery.
- Known hypersensitivity to the components of the investigational product.
- Subjects with a known allergy to FD\&C Blue #1 dye
Show all 24Show fewer
- Subjects with an infection present at the surgical site
- Subjects with an infection indicated by any one of the following: clinical diagnosis of infection, fever, positive urine culture, positive blood culture, positive chest X-ray.
- Female subjects of childbearing potential with a positive pregnancy test or intent to become pregnant during the clinical study period.
- Female subjects who are nursing.
- Exposure to another investigational drug or device clinical trial within 30 days prior to enrollment or anticipated in the 60 day follow-up period.
- Subjects with severely altered renal or hepatic function, with a compromised immune system or autoimmune disease who can NOT receive hydrogel sealant.
- Subjects with penetratring traumatic injuries to the head with damage to the dura
- Dural injury during craniotomy/craniectomy that cannot be eliminated by widening the craniotomy/craniectomy to recreate the native dural cuff.
- Patient has a gap between durotomy edges of greater than 2mm after primary dural closure.
- Approaches that would not allow sutured dural closure such as trans-sphenoidal or trans-labirinthine-/petrosal/-mastoid. Superficial penetration of mastoid air cells are allowed.
- Use of implants made of synthetic materials coming into direct contact with dura
- Use of other fibrin sealants or PEG-based sealants on the dural closure. Approved fibrin sealants may be used for hemostasis if not in contact with the dura.
- Hydrocephalus, except occlusive hydrocephalus caused by posterior fossa pathology or incompletely open cerebrospinal fluid pathways, to be treated during surgical procedure.
- Placement of Gliadel Wafers
- Intersecting durotomy scars in the surgical path from a previous operation that cannot be completely removed by the planned dural resection.
- Two or more separate cranial dural defects, including defects from ventricular cannulation and ventriculo-peritoneal shunting.
- Subjects with any other intra-operative findings identified by the surgeon that may preclude the conduct of the study procedure.
- Confined bony structures where nerves are present where neural compression may result due to swelling.
Trial locations and contacts
26 sites in 6 countries.
26 sites in 6 countries
United States13 sites
Clinical Investigation Site #24
Ann Arbor, Michigan, 48109
Clinical Investigation Site #15
Baltimore, Maryland, 21201
Clinical Investigation Site #11
Boston, Massachusetts, 02215
Clinical Investigation Site #14
Cincinnati, Ohio, 45219
Clinical Investigation Site #22
Indianapolis, Indiana, 46202
Clinical Investigation Site #18
Jacksonville, Florida, 32207
Clinical Investigation Site #27
Los Angeles, California, 90033
Clinical Investigation Site #20
New Brunswick, New Jersey, 08903
Clinical Investigation Site #10
New Orleans, Louisiana, 70121
Clinical Investigation Site #12
New York, New York, 10065
Clinical Investigation Site #21
Philadelphia, Pennsylvania, 19107
Clinical Investigation Site #17
Sacramento, California, 95817
Clinical Investigation Site #19
Tampa, Florida, 33606
United Kingdom5 sites
Clinical Investigation Site #35
London, England
Clinical Investigation Site #32
Middlesbrough, England
Clinical Investigation Site #35
Nottingham, England
Clinical Investigation Site #30
Oxford, England
Clinical Investigation Site #31
Salford, England
Australia4 sites
Clinical Investigation Site #54
Adelaide, South Australia, 5000
Clinical Investigation Site #50
Melbourne, Victoria
Clinical Investigation Site #52
Richmond, Victoria, 3121
Clinical Investigation Site #51
Sydney, New South Wales, 2109
Belgium2 sites
Clinical Investigation Site #40
Genk
Clinical Investigation Site #41
Leuven
About this study
Official title: A Single-Blinded, Randomized, Controlled Study to Evaluate the Safety and Effectiveness of EVICEL® Fibrin Sealant (Human) Compared to a Hydrogel Sealant as an Adjunct to Sutured Dural Repair
The objective of this study is to evaluate the safety and efficacy of EVICEL® Fibrin Sealant (Human) for use as an adjunct to sutured dural repair in cranial surgery.
- Conditions
- Cerebrospinal Fluid Leak
- Being tested
- EVICEL Fibrin Sealant, Hydrogel sealant
- Keywords
- Fibrin sealant, CSF leak
- Medical subject headings
- Cerebrospinal Fluid Leak, Cerebrospinal Fluid Otorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EVICEL Fibrin SealantBiological
Also called fibrin sealant
Hydrogel sealantDevice
| Study group | Role | What they receive |
|---|---|---|
| EVICEL Fibrin Sealant | Experimental | EVICEL is a human plasma-derived fibrin sealant composed of two components - thrombin and fibrinogen Receives: Biological: EVICEL Fibrin Sealant |
| Hydrogel sealant | Active comparator | The sealant is composed of two solutions, a polyethylene glycol (PEG) ester solution and a trilysine amine solution Receives: Device: Hydrogel sealant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period)
The primary endpoint was the proportion of subjects that had no inter-operative CSF leak following Valsalva maneuver and no CSF leak or pseudomeningocele in the surgical area during the 30-day follow-up period
Measured: Intraoperatively through 30-day follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2015 (estimated)
- Study start1 Jul 2015
- Primary completion13 Sep 2017
- Study completion12 Oct 2017
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 234 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ethicon, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard Kocharian, MD, PhD, Study director, Ethicon, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02457546
- Sponsor's protocol ID
- BIOS-14-002
- Other IDs
- 2014-003954-15, 2014
- Status last verified
- Jan 2019
- First submitted
- 27 May 2015
- Last updated
- 10 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Green AL, Arnaud A, Batiller J, Eljamel S, Gauld J, Jones P, Martin D, Mehdorn M, Ohman J, Weyns F. A multicentre, prospective, randomized, controlled study to evaluate the use of a fibrin sealant as an adjunct to sutured dural repair. Br J Neurosurg. 2015 Feb;29(1):11-17. doi: 10.3109/02688697.2014.948808. Epub 2014 Aug 12.
PubMed 25112563
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Blinded, Randomized, Controlled Study to Evaluate the Safety and Effectiveness of EVICEL® Fibrin Sealant (Human) Compared to a Hydrogel Sealant as an Adjunct to Sutured Dural Repair
- ClinicalTrials.gov ID
- NCT02457546
- Acronym / sponsor ID
- BIOS-14-002
- Conditions
- Cerebrospinal Fluid Leak
- Keywords
- Fibrin sealant, CSF leak
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 234 participants (actual)
- Lead sponsor
- Ethicon, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Jul 2015 (actual)
- Primary completion
- 13 Sep 2017 (actual)
- Study completion
- 12 Oct 2017 (actual)
- First posted
- 29 May 2015 (estimated)
- Results
- Posted 4 Dec 2018
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 EVICEL® Fibrin Sealant (Human) 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 |
|---|---|---|
| EVICEL Fibrin Sealant | Experimental | Biological: EVICEL Fibrin SealantEVICEL is a human plasma-derived fibrin sealant composed of two components - thrombin and fibrinogen |
| Hydrogel sealant | Active comparator | Device: Hydrogel sealantThe sealant is composed of two solutions, a polyethylene glycol (PEG) ester solution and a trilysine amine solution |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subjects ≥18 years of age undergoing craniotomy/craniectomy for pathological processes in the supratentorial region or posterior fossa
- Subjects or legally authorized representatives must be willing to participate in the study and provide written informed consent.
- Surgical wound classification Class I
- The cuff of native dura along the craniotomy edge on each side is adequate, based on surgeon's judgment, to facilitate suturing and to allow for sufficient surface area for adherence of the investigational product
- Presence of intra-operative cerebrospinal fluid (CSF) leakage following primary dural closure or after Valsalva maneuver
Key exclusion criteria (24 listed)
- Subjects with a dural lesion from a recent surgery that still has the potential for CSF leakage.
- Chemotherapy within 30-days prior to enrollment or scheduled within 7-days following surgery
- Radiation therapy to the head within 30-days prior to enrollment or scheduled within 7-days following surgery
- A previous craniotomy/craniectomy within 6 months prior to the study surgery.
- Known hypersensitivity to the components of the investigational product.
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 |
|---|---|---|
| EVICEL Fibrin SealantAlso: fibrin sealant | Biological | EVICEL Fibrin Sealant |
| Hydrogel sealant | Device | Hydrogel sealant |
Primary outcome
Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period)
Time frame: Intraoperatively through 30-day follow-up
The primary endpoint was the proportion of subjects that had no inter-operative CSF leak following Valsalva maneuver and no CSF leak or pseudomeningocele in the surgical area during the 30-day follow-up period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25112563Green AL, Arnaud A, Batiller J, Eljamel S, Gauld J, Jones P, Martin D, Mehdorn M, Ohman J, Weyns F. A multicentre, prospective, randomized, controlled study to evaluate the use of a fibrin sealant as an adjunct to sutured dural repair. Br J Neurosurg. 2015 Feb;29(1):11-17. doi: 10.3109/02688697.2014.948808. Epub 2014 Aug 12.
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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.
Richard Kocharian, MD, PhD study director
Ethicon, Inc.
26 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing EVICEL Fibrin Sealant and Hydrogel sealant in people with Cerebrospinal Fluid Leak, run by Ethicon, Inc. at 26 sites in 6 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 24 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 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, United Kingdom, Australia, Belgium, Canada and 1 more country. 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 4 Dec 2018). 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?
Primary Effectiveness Endpoint Success Number of Successes (Subjects That Had no Inter-operative CSF Leak Following Valsalva Maneuver and no CSF Leak or Pseudomeningocele in the Surgical Area During the 30-day Follow-up Period) (time frame: Intraoperatively through 30-day follow-up). 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 NCT02457546, which also lists 1 linked publication.
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 Jan 2019.