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.

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.

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.

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.

The full analysis set (FAS) consisted of all randomized participants.

Up to 33 days

The safety analysis set consisted of all participants who received treatment.