PDF(Pubmed)
Abstract：
OBJECTIVE: 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®.
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).
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).
摘要：
目的：脑脊液（CSF）泄漏是硬膜内颅手术的一个有挑战性的并发症，儿童尤其处于危险之中。硬脑膜密封剂的使用赋予成人保护，但是儿科研究很少。我们评估了Evicel®纤维蛋白密封剂作为头颅手术儿童原发性硬膜缝合的辅助手段的安全性和有效性。
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)。
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)。
