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®.
CONCLUSIONS: 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).
方法:一项多中心试验前瞻性招募接受颅神经外科手术的儿科受试者(<18岁),完成一期硬脑膜缝合修复后,有脑脊液渗漏。根据EMAEvicel®儿科调查计划的同意,40名受试者在术中2:1随机分配至Evicel®或其他缝线(“缝线”)。数据分析是描述性的。疗效终点为治疗成功率,成功定义为挑衅性Valsalva动作后的术中水密闭合(主要终点)。安全终点为术后脑脊液漏(切口脑脊液漏,假性脑膜膨出或两者兼有)和手术部位并发症(次要终点)。
结果:40名受试者(0.6-17岁)被随机分为Evicel®(N=25)或Sutures(N=15)(意向治疗)。颅内肿瘤是最常见的适应症,手术多为幕上开颅手术。Evicel®的成功率为92.0%,缝线为33.3%,估计成功率为2.76(Farrington-Manning95%CI[1.53,6.16])。每个方案和安全性集中的敏感性分析显示出类似的结果。尽管抢救治疗率较高,与Evicel®相比,缝线术后脑脊液漏和伤口并发症的发生率更高.
结论:这项小规模前瞻性研究表明,在儿科人群中,Evicel®治疗作为原发性缝合硬脑膜闭合的辅助治疗是安全有效的。与额外的缝线相比,Evicel®与术后脑脊液漏和手术部位并发症减少有关。(试验登记:试验登记为NCT02309645和EudraCT2013-003558-26)。