The Paediatric EVICEL® Neuro Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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CSF Leak

Intervention / Treatment
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* Biological: EVICEL® Fibrin Sealant
* Other: Sutures Only


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EVICEL® Fibrin Sealant<br>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 | Biological: EVICEL® Fibrin Sealant<br>* 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.<br>* Other names: EVICEL, fibrin sealant;|
| Other: Sutures Only<br>Subjects randomized to control will receive additional dural repair sutures as deemed necessary by the surgeon to attempt to achieve a watertight closure. | Other: Sutures Only<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Intraoperative (up to 1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing CSF Leakage Within 7 Days Post-operatively | Number of participants experiencing CSF leakage within 7 days post-operatively were reported. | 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. | 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. | 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. | Up to 33 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibrin sealant, CSF leak