背景:先前对112名受试者进行了III期试验,研究了尼莫地平在前庭神经鞘瘤(VS)手术中的预防性治疗,对保留面部和耳蜗神经功能没有明显的有益作用,尽管应考虑保护面神经功能是主要结果。然而,与对照组相比,尼莫地平组术后听力损失的风险降低了一半(OR0.49;95%CI0.18~1.30;p=0.15).因此,这项III期扩展试验研究了VS手术中预防性使用尼莫地平保护听力的有效性和安全性.
方法:这是一个随机的,多中心,双臂,开放标签III期试验,专家审查盲法和中期分析两阶段.将136名具有显微手术切除VS(KoosI-IV)和可使用的术前听力(Gardner-Robertson量表(GR)1-3)适应症的成年人分配给治疗(静脉注射尼莫地平1-2mg/h从手术前一天到术后第五天和标准护理)或对照组(仅手术和标准护理)。试验的主要终点是根据GR1-3和GR4-5(二元)在出院前测量的术后耳蜗神经功能。听力功能将通过带有言语辨别的术前和术后测听来确定,这将由盲目的专家审阅者进行评估。此外,将使用标准化问卷分析患者报告的结局.
结论:预防性胃肠外尼莫地平治疗可能对VS手术中的听力保护有积极作用,并将改善患者的生活质量。计划进行进一步的二次分析。除了剂量依赖性低血压,尼莫地平被认为是一种安全的药物。在未来,预防性尼莫地平治疗可作为VS手术的常规药物。VS可以被认为是临床评估神经保护的理想模型,因为听力结果可以通过公认的标准进行分类。尼莫地平的有益效果可能会转移到其他具有神经风险的外科手术中,并可能对基础研究产生影响。
背景:EudraCT2019-002317-19,DRKS00019107。2020年5月8日。
BACKGROUND: A previously performed phase III
trial on 112 subjects investigating prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery showed no clear beneficial effects on preservation of facial and cochlear nerve functions, though it should be considered that protection of facial nerve function was the primary outcome. However, the risk for postoperative hearing loss was halved in the nimodipine group compared to the control group (OR 0.49; 95% CI 0.18-1.30; p = 0.15). Accordingly, this phase III extension
trial investigates the efficacy and safety of prophylactic nimodipine for hearing preservation in VS surgery.
METHODS: This is a randomized, multi-center, two-armed, open-label phase III
trial with blinded expert review and two-stage with interim analysis. Three hundred thirty-six adults with the indication for microsurgical removal of VS (Koos I-IV) and serviceable preoperative hearing (Gardner-Robertson scale (GR) 1-3) are assigned to either the therapy (intravenous nimodipine 1-2 mg/h from the day before surgery until the fifth postoperative day and standard of care) or the control group (surgery only and standard of care). The primary endpoint of the
trial is postoperative cochlear nerve function measured before discharge according to GR 1-3 versus GR 4-5 (binary). Hearing function will be determined by pre- and postoperative audiometry with speech discrimination, which will be evaluated by a blinded expert reviewer. Furthermore, patient-reported outcomes using standardized questionnaires will be analyzed.
CONCLUSIONS: Prophylactic parenteral nimodipine treatment may have a positive effect on hearing preservation in VS surgery and would improve patient\'s quality of life. Further secondary analyses are planned. Except for dose-depending hypotension, nimodipine is known as a safe drug. In the future, prophylactic nimodipine treatment may be recommended as a routine medication in VS surgery. VS can be considered as an ideal model for clinical evaluation of neuroprotection, since hearing outcome can be classified by well-recognized criteria. The beneficial effect of nimodipine may be transferable to other surgical procedures with nerves at risk and may have impact on basic research.
BACKGROUND: EudraCT 2019-002317-19, DRKS00019107 . 8th May 2020.