Safety and effectiveness of evicel® fibrin sealant as an adjunct to sutured dural repair in children undergoing cranial neurosurgery

Gnanamurthy Sivakumar; Shailendra Magdum; Kristian Aquilina; Jothy Kandasamy; Vivek Josan; Bogdan Ilie; Ellie Barnett; Richard Kocharian; Benedetta Pettorini

doi:10.1007/s00381-024-06434-4

Safety and effectiveness of evicel^® fibrin sealant as an adjunct to sutured dural repair in children undergoing cranial neurosurgery

Childs Nerv Syst. 2024 May 10. doi: 10.1007/s00381-024-06434-4. Online ahead of print.

Authors

Gnanamurthy Sivakumar¹, Shailendra Magdum², Kristian Aquilina³, Jothy Kandasamy⁴, Vivek Josan⁵, Bogdan Ilie⁶, Ellie Barnett⁷, Richard Kocharian⁶, Benedetta Pettorini⁸

Affiliations

¹ Leeds General Infirmary, Great George Street, Leeds, LS1 3EX, UK. gsivakumar1@nhs.net.
² John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
³ Great Ormond Street Hospital, London, WC1N 3JH, UK.
⁴ Royal Hospital for Sick Children, Sciennes Road, Edinburgh, EH9 1LF, UK.
⁵ Royal Manchester Children's Hospital, Oxford Road, Manchester, M13 9WL, UK.
⁶ Ethicon, Inc., 1000 US-202 South, Raritan, NJ, 08869, USA.
⁷ Ethicon, Inc., 8 Deer Park, Livingston, EH54 8AF, United Kingdom.
⁸ Alder Hey Children's Hospital, Eaton Road, Liverpool, L12 2AP, UK.

PMID: 38727726
DOI: 10.1007/s00381-024-06434-4

Abstract

Purpose: Cerebrospinal fluid (CSF) leakage is a challenging complication of intradural cranial surgery, and children are particularly at risk. The use of dural sealants confers protection in adults, but pediatric studies are scarce. We evaluated the safety and efficacy of Evicel^® fibrin sealant as an adjunct to primary dural suturing in children undergoing cranial surgery.

Methods: A multicenter trial prospectively enrolled pediatric subjects (< 18 years) undergoing cranial neurosurgery who, upon completion of primary sutured dural repair, experienced CSF leakage. As agreed by the EMA Evicel^® Pediatric Investigation Plan, 40 subjects were intra-operatively randomized 2:1 to Evicel^® or additional sutures ('Sutures'). Data analysis was descriptive. The efficacy endpoint was treatment success rate, with success defined as intra-operative watertight closure after provocative Valsalva maneuver (primary endpoint). Safety endpoints were postoperative CSF leakage (incisional CSF leakage, pseudomeningocele or both) and surgical site complications (secondary endpoints).

Results: Forty subjects (0.6-17 years) were randomized to Evicel^® (N = 25) or Sutures (N = 15) (intention-to-treat). Intracranial tumor was the most common indication and procedures were mostly supratentorial craniotomies. Success rates were 92.0% for Evicel^® and 33.3% for Sutures, with a 2.76 estimated ratio of success rates (Farrington-Manning 95% CI [1.53, 6.16]). Sensitivity analyses in per-protocol and safety sets showed similar results. Despite a higher rescue treatment rate, the frequencies of postoperative CSF leakage and wound complications were higher for Sutures than for Evicel^®.

Conclusion: This small-scale prospective study shows Evicel^® treatment to be safe and effective as an adjunct to primary sutured dura mater closure in a pediatric population. Compared to additional sutures, Evicel^® was associated with reduced postoperative CSF leakage and surgical site complications. (Trial registration: The trial was registered as NCT02309645 and EudraCT 2013-003558-26).

Keywords: Cerebrospinal fluid leak; Dural sealing; Fibrin sealant; Pediatric neurosurgery.

Associated data

ClinicalTrials.gov/NCT02309645