The Paediatric EVICEL® Neuro Study
Primary Purpose
CSF Leak
Status
Terminated
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
EVICEL® Fibrin Sealant
Sutures Only
Sponsored by
About this trial
This is an interventional treatment trial for CSF Leak focused on measuring fibrin sealant, CSF leak
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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;
- 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.
Sites / Locations
- Clinical Investigation Site #24
- Clinical Investigation Site #22
- Clinical Investigation Site #21
- St George's University Hospitals NHS Foundation Trust
- Clinical Investigation Site #25
- Clinical Investigation Site #23
- Clinical Investigation Site #20
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
EVICEL® Fibrin Sealant
Sutures Only
Arm Description
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
Subjects randomized to control will receive additional dural repair sutures as deemed necessary by the surgeon to attempt to achieve a watertight closure.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Number of Participants Experiencing CSF Leakage Within 7 Days Post-operatively
Number of participants experiencing CSF leakage within 7 days post-operatively were reported.
Number of Participants Experiencing CSF Leakage Within 33 Days Post-operatively
Number of participants experiencing CSF leakage within 33 days post-operatively were reported.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02309645
Brief Title
The Paediatric EVICEL® Neuro 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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why 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.
Study Start Date
October 1, 2014 (Actual)
Primary Completion Date
August 17, 2021 (Actual)
Study Completion Date
September 17, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ethicon, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CSF Leak
Keywords
fibrin sealant, CSF leak
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EVICEL® Fibrin Sealant
Arm Type
Experimental
Arm Description
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
Arm Title
Sutures Only
Arm Type
Other
Arm Description
Subjects randomized to control will receive additional dural repair sutures as deemed necessary by the surgeon to attempt to achieve a watertight closure.
Intervention Type
Biological
Intervention Name(s)
EVICEL® Fibrin Sealant
Other Intervention Name(s)
EVICEL, fibrin sealant
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Sutures Only
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Success (Intraoperative Watertight Closure) in the Treatment of Intraoperative Cerebrospinal Fluid (CSF) Leakage
Description
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.
Time Frame
Intraoperative (up to 1 day)
Secondary Outcome Measure Information:
Title
Number of Participants Experiencing CSF Leakage Within 7 Days Post-operatively
Description
Number of participants experiencing CSF leakage within 7 days post-operatively were reported.
Time Frame
Up to 7 days post-operatively
Title
Number of Participants Experiencing CSF Leakage Within 33 Days Post-operatively
Description
Number of participants experiencing CSF leakage within 33 days post-operatively were reported.
Time Frame
Up to 33 days post-operatively
Title
Number of Participants With Adverse Events (AEs)
Description
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.
Time Frame
Up to 33 days
Title
Number of Participants With Surgical Site Infections (SSI) According to National Healthcare Safety Network (NHSN) Criteria Within 33 Days Post-operatively
Description
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.
Time Frame
Up to 33 days
10. Eligibility
Sex
All
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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;
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Kocharian, MD, PhD
Organizational Affiliation
Ethicon, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Investigation Site #24
City
Edinburgh
Country
United Kingdom
Facility Name
Clinical Investigation Site #22
City
Leeds
Country
United Kingdom
Facility Name
Clinical Investigation Site #21
City
Liverpool
Country
United Kingdom
Facility Name
St George's University Hospitals NHS Foundation Trust
City
London
ZIP/Postal Code
SW17 0QT
Country
United Kingdom
Facility Name
Clinical Investigation Site #25
City
London
Country
United Kingdom
Facility Name
Clinical Investigation Site #23
City
Manchester
Country
United Kingdom
Facility Name
Clinical Investigation Site #20
City
Oxford
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
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The Paediatric EVICEL® Neuro Study
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