CSF LeakPhase 3NCT02309645
The Paediatric EVICEL® Neuro Study
A Phase 3 study testing EVICEL® Fibrin Sealant and Sutures Only in people with CSF Leak, run by Ethicon, Inc. at 7 sites in United Kingdom.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of EVICEL® when used for suture-line sealing in dura-mater closure in elective or urgent paediatric cranial neurosurgery to provide intraoperative watertight closure. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- CSF Leak
- What is being tested?
- EVICEL® Fibrin Sealant and Sutures Only
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 7 sitesUnited Kingdom
- Study dates
- 1 Oct 2014to 17 Sep 2021
- 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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patient undergoing elective or urgent craniotomy/craniectomy for pathological processes in the posterior fossa (such as benign or malignant tumors, vascular malformation, and Chiari 1 malformations) or in the supratentorial region and who are demonstrated to have persistent CSF leakage following primary attempt at suture closure of the dural incision;
- Administration of perioperative antibiotic prophylaxis;
- Patients who are less than 18 years of age;
- Patients who are able and willing to comply with the procedures required by the protocol;
- The subject's parent/legal guardian must be willing to give permission for the subject to participate in the trial, and provide written informed consent for the subject. In addition, assent must be obtained from paediatric subjects who possess the intellectual and emotional ability to comprehend the concepts involved in the trial.
- Surgical wound classification Class I (refer to Appendix II). Penetration of mastoid air cells during partial mastoidectomy is permitted;
- The cuff of native dura along the craniotomy edge on each side is wide enough based on surgeon's judgment to facilitate suturing and to allow for sufficient surface area for adherence of the investigational product.
Who cannot join
- Subjects with a dura lesion from a recent surgery that still has the potential for CSF leakage;
- Conditions or treatments significantly compromising the immune system (such as AIDS);
- Known hypersensitivity to the components (human fibrinogen, arginine hydrochloride, glycine, sodium chloride, sodium citrate, calcium chloride, human thrombin, human albumin, mannitol and sodium acetate) of the investigational product;
- Hydrocephalus, except occlusive hydrocephalus caused by posterior fossa pathology to be treated.
- Existing CSF (ventricular, etc.) drains, shunts, Cushing/Dandy cannulation or Burr holes which damage the dura;
- Female subjects of childbearing potential with a positive urine or serum pregnancy test within 24 hours prior to surgery;
Show all 18Show fewer
- Female subjects who are breastfeeding or intend to become pregnant during the clinical study period;
- Participation in another clinical trial with exposure to another investigational drug or device within 30 days prior to enrollment or expected during the study period;
- Scheduled or foreseeable surgery within the follow-up period.
- Dura injury during craniotomy/craniectomy that cannot be eliminated by widening the craniotomy/craniectomy to recreate the native dura cuff;
- Use of implants made of synthetic materials coming into direct contact with dura (e.g., PTFE patches, shunts, ventricular and subdural drains);
- Planned use of dural patches after primary suture closure of the dura;
- Placement of Gliadel Wafers;
- Persistent signs of increased brain turgor;
- Patient has a gap between durotomy edges of greater than 2mm after primary dural closure.
- Intersecting durotomy scars in the surgical path from a previous operation that cannot be completely removed by the planned dura resection;
- Two or more separate dura defects;
- Major intraoperative complications that require resuscitation or deviation from the planned surgical procedure.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United Kingdom7 sites
Clinical Investigation Site #24
Edinburgh
Clinical Investigation Site #22
Leeds
Clinical Investigation Site #21
Liverpool
St George's University Hospitals NHS Foundation Trust
London, SW17 0QT
Clinical Investigation Site #25
London
Clinical Investigation Site #23
Manchester
Clinical Investigation Site #20
Oxford
About this study
Official title: A Prospective Randomized Controlled Study Evaluating the Safety and Efficacy of EVICEL® Used for Suture-Line Sealing in Dura-Mater Closure During Paediatric Neurosurgical Cranial Procedures
The purpose of this study is to evaluate the safety and efficacy of EVICEL® when used for suture-line sealing in dura-mater closure in elective or urgent paediatric cranial neurosurgery to provide intraoperative watertight closure.
Read the detailed description
This is a prospective randomized, open-label, multi-center controlled study evaluating the effectiveness of EVICEL® as an adjunct to sutured dural closure compared to control to obtain an intraoperative watertight dural closure.
Paediatric subjects, undergoing elective or urgent craniotomy/craniectomy for pathological processes in the posterior fossa (such as benign or malignant tumors, vascular malformations, and Chiari 1 malformations) or in the supratentorial region and who were demonstrated to have persistent cerebrospinal fluid (CSF) leakage following a primary attempt at suture closure of the dural incision.
Paediatric subjects for this study are classified as:
- Newborn infants (birth to 27 days. Pre-term newborn infants born ≤ 37 weeks gestation will be included within the group)
- Infants and toddlers (28 days to <24 months)
- Children (2 to 11 years)
- Adolescents (12 to <18 years) 42 paediatric subjects with intra-operative cerebrospinal fluid (CSF) leak following primary suturing of the dura will be randomized in a 2:1 allocation ratio and will be stratified by surgical procedure, posterior fossa or supratentorial to either EVICEL® Fibrin Sealant (Human) or additional dural sutures.
Subjects will be followed post-operatively through discharge and for 30 days (±3 days) post-surgery. The incidence of CSF leaks will be assessed within 5 days (± 2 days) and 30 days (±3 days) post-operatively as detected by any of the following: clinical observation, diagnostic testing or the need for surgical intervention to treat a CSF leak or pseudomeningocele.
- Conditions
- CSF Leak
- Being tested
- EVICEL® Fibrin Sealant, Sutures Only
- Keywords
- fibrin sealant, CSF leak
- Medical subject headings
- 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 EVICEL, fibrin sealant
Subjects randomized to receive EVICEL® Fibrin Sealant (Human), a thin layer will be applied to the entire length of the suture line and the adjacent area to at least 5mm away, including all suture holes.
Sutures OnlyOther
Subjects randomized to Control (Additional Sutures) will receive additional dural repair sutures applied immediately to the dural suture line after randomization as deemed necessary by the surgeon.
| Study group | Role | What they receive |
|---|---|---|
| EVICEL® Fibrin Sealant | Experimental | EVICEL® is a human plasma-derived fibrin sealant. EVICEL® consists of two components: a concentrate of Human Clottable Protein (referred to as Biological Component 2; BAC2) and a solution of Human Thrombin. No material of animal origin is present in the product Receives: Biological: EVICEL® Fibrin Sealant |
| Sutures Only | Other | Subjects randomized to control will receive additional dural repair sutures as deemed necessary by the surgeon to attempt to achieve a watertight closure. Receives: Other: Sutures Only |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Success (Intraoperative Watertight Closure) in the Treatment of Intraoperative Cerebrospinal Fluid (CSF) Leakage
Percentage of participants with success (intraoperative watertight closure) in the treatment of intraoperative CSF leakage were reported. Success is defined as no CSF leakage from dural repair intraoperatively, during Valsalva Maneuver 20-25 centimeters (cm) water (H2O) for 5-10 seconds.
Measured: Intraoperative (up to 1 day)
Secondary outcomes (4)
Number of Participants Experiencing CSF Leakage Within 7 Days Post-operatively
Number of participants experiencing CSF leakage within 7 days post-operatively were reported.
Measured: Up to 7 days post-operatively
Number of Participants Experiencing CSF Leakage Within 33 Days Post-operatively
Number of participants experiencing CSF leakage within 33 days post-operatively were reported.
Measured: Up to 33 days post-operatively
Number of Participants With Adverse Events (AEs)
An adverse event was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE (also referred to as an adverse experience) could be any unfavorable and unintended sign, symptom, or disease temporarily associated with the use of a drug, without judgment about causality. Since post-operative pain was an expected outcome of this type of surgery, for purposes of this study, only exacerbations of expected post-operative pain based on the investigator's judgment was reported as an AE.
Measured: Up to 33 days
Number of Participants With Surgical Site Infections (SSI) According to National Healthcare Safety Network (NHSN) Criteria Within 33 Days Post-operatively
Number of participants with SSI according to NHSN criteria within 33 days post-operatively were reported. NHSN CRITERIA states that infections occur within 33 days after the operation and infection involves only skin or subcutaneous tissue of the incision and at least one of the following: a) Purulent drainage, with or without laboratory confirmation, from the superficial incision; b) Organisms isolated from an aseptically obtained culture or fluid or tissue from the superficial incision; c) At least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness, or heat and superficial incision is deliberately open by surgeon, unless incision is culture-negative; d) Diagnosis of superficial incisional SSI by the surgeon or attending physician.
Measured: Up to 33 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2014 (estimated)
- Study start1 Oct 2014
- Primary completion17 Aug 2021
- Study completion17 Sep 2021
Why it stopped: Study completed the required elements (40 paediatric subjects) per regulatory requirement. The study enrolled 40/42 subjects. No safety signals were identified. No changes required to the statistical analysis as described in the protocol.
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 CSF 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 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
- NCT02309645
- Sponsor's protocol ID
- BIOS-13-006
- Other IDs
- 2013-003558-26
- Status last verified
- Aug 2022
- First submitted
- 2 Oct 2014
- Last updated
- 14 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
Sivakumar G, Magdum S, Aquilina K, Kandasamy J, Josan V, Ilie B, Barnett E, Kocharian R, Pettorini B. Safety and effectiveness of Evicel(R) fibrin sealant as an adjunct to sutured dural repair in children undergoing cranial neurosurgery. Childs Nerv Syst. 2024 Sep;40(9):2735-2745. doi: 10.1007/s00381-024-06434-4. Epub 2024 May 10.
PubMed 38727726
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Controlled Study Evaluating the Safety and Efficacy of EVICEL® Used for Suture-Line Sealing in Dura-Mater Closure During Paediatric Neurosurgical Cranial Procedures
- ClinicalTrials.gov ID
- NCT02309645
- Acronym / sponsor ID
- BIOS-13-006
- Conditions
- CSF Leak
- Keywords
- fibrin sealant, CSF leak
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study completed the required elements (40 paediatric subjects) per regulatory requirement. The study enrolled 40/42 subjects. No safety signals were identified. No changes required to the statistical analysis as described in the protocol.
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Ethicon, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Oct 2014 (actual)
- Primary completion
- 17 Aug 2021 (actual)
- Study completion
- 17 Sep 2021 (actual)
- First posted
- 5 Dec 2014 (estimated)
- Results
- Posted 14 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and efficacy of EVICEL® when used for suture-line sealing in dura-mater closure in elective or urgent paediatric cranial neurosurgery to provide intraoperative watertight closure.
Detailed description
This is a prospective randomized, open-label, multi-center controlled study evaluating the effectiveness of EVICEL® as an adjunct to sutured dural closure compared to control to obtain an intraoperative watertight dural closure.
Paediatric subjects, undergoing elective or urgent craniotomy/craniectomy for pathological processes in the posterior fossa (such as benign or malignant tumors, vascular malformations, and Chiari 1 malformations) or in the supratentorial region and who were demonstrated to have persistent cerebrospinal fluid (CSF) leakage following a primary attempt at suture closure of the dural incision.
Paediatric subjects for this study are classified as:
- Newborn infants (birth to 27 days. Pre-term newborn infants born ≤ 37 weeks gestation will be included within the group)
- Infants and toddlers (28 days to <24 months)
- Children (2 to 11 years)
- Adolescents (12 to <18 years) 42 paediatric subjects with intra-operative cerebrospinal fluid (CSF) leak following primary suturing of the dura will be randomized in a 2:1 allocation ratio and will be stratified by surgical procedure, posterior fossa or supratentorial to either EVICEL® Fibrin Sealant (Human) or additional dural sutures.
Subjects will be followed post-operatively through discharge and for 30 days (±3 days) post-surgery. The incidence of CSF leaks will be assessed within 5 days (± 2 days) and 30 days (±3 days) post-operatively as detected by any of the following: clinical observation, diagnostic testing or the need for surgical intervention to treat a CSF leak or pseudomeningocele.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EVICEL® Fibrin Sealant | Experimental | Biological: EVICEL® Fibrin SealantEVICEL® is a human plasma-derived fibrin sealant. EVICEL® consists of two components: a concentrate of Human Clottable Protein (referred to as Biological Component 2; BAC2) and a solution of Human Thrombin. No material of animal origin is present in the product |
| Sutures Only | Other | Other: Sutures OnlySubjects randomized to control will receive additional dural repair sutures as deemed necessary by the surgeon to attempt to achieve a watertight closure. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Patient undergoing elective or urgent craniotomy/craniectomy for pathological processes in the posterior fossa (such as benign or malignant tumors, vascular malformation, and Chiari 1 malformations) or in the supratentorial region and who are demonstrated to have persistent CSF leakage following primary attempt at suture closure of the dural incision;
- Administration of perioperative antibiotic prophylaxis;
- Patients who are less than 18 years of age;
- Patients who are able and willing to comply with the procedures required by the protocol;
- The subject's parent/legal guardian must be willing to give permission for the subject to participate in the trial, and provide written informed consent for the subject. In addition, assent must be obtained from paediatric subjects who possess the intellectual and emotional ability to comprehend the concepts involved in the trial.
Key exclusion criteria (18 listed)
- Subjects with a dura lesion from a recent surgery that still has the potential for CSF leakage;
- Conditions or treatments significantly compromising the immune system (such as AIDS);
- Known hypersensitivity to the components (human fibrinogen, arginine hydrochloride, glycine, sodium chloride, sodium citrate, calcium chloride, human thrombin, human albumin, mannitol and sodium acetate) of the investigational product;
- Hydrocephalus, except occlusive hydrocephalus caused by posterior fossa pathology to be treated.
- Existing CSF (ventricular, etc.) drains, shunts, Cushing/Dandy cannulation or Burr holes which damage the dura;
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: EVICEL, fibrin sealantSubjects randomized to receive EVICEL® Fibrin Sealant (Human), a thin layer will be applied to the entire length of the suture line and the adjacent area to at least 5mm away, including all suture holes. | Biological | EVICEL® Fibrin Sealant |
| Sutures OnlySubjects randomized to Control (Additional Sutures) will receive additional dural repair sutures applied immediately to the dural suture line after randomization as deemed necessary by the surgeon. | Other | Sutures Only |
Primary outcome
Percentage of Participants With Success (Intraoperative Watertight Closure) in the Treatment of Intraoperative Cerebrospinal Fluid (CSF) Leakage
Time frame: Intraoperative (up to 1 day)
Percentage of participants with success (intraoperative watertight closure) in the treatment of intraoperative CSF leakage were reported. Success is defined as no CSF leakage from dural repair intraoperatively, during Valsalva Maneuver 20-25 centimeters (cm) water (H2O) for 5-10 seconds.
4 secondary outcomes
Number of Participants Experiencing CSF Leakage Within 7 Days Post-operatively
Time frame: Up to 7 days post-operatively
Number of Participants Experiencing CSF Leakage Within 33 Days Post-operatively
Time frame: Up to 33 days post-operatively
Number of Participants With Adverse Events (AEs)
Time frame: Up to 33 days
Number of Participants With Surgical Site Infections (SSI) According to National Healthcare Safety Network (NHSN) Criteria Within 33 Days Post-operatively
Time frame: Up to 33 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38727726Sivakumar G, Magdum S, Aquilina K, Kandasamy J, Josan V, Ilie B, Barnett E, Kocharian R, Pettorini B. Safety and effectiveness of Evicel(R) fibrin sealant as an adjunct to sutured dural repair in children undergoing cranial neurosurgery. Childs Nerv Syst. 2024 Sep;40(9):2735-2745. doi: 10.1007/s00381-024-06434-4. Epub 2024 May 10.
- Individual participant dataSharing planned: Yes
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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.
Richard Kocharian, MD, PhD study director
Ethicon, Inc.
7 sites in 1 country: 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 Sutures Only in people with CSF Leak, run by Ethicon, Inc. at 7 sites in United Kingdom.
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 7 inclusion and 18 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: stopped early, as of the sponsor's last update on 14 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom. 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 14 Jul 2023). 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?
Percentage of Participants With Success (Intraoperative Watertight Closure) in the Treatment of Intraoperative Cerebrospinal Fluid (CSF) Leakage (time frame: Intraoperative (up to 1 day)). 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 NCT02309645, 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 14 Jul 2023.