Department of Neurosurgery, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06097, Halle (Saale), Germany.
Coordination Centre for Clinical Trials, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Trials. 2021 Jul 22;22(1):475. doi: 10.1186/s13063-021-05417-z.
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.
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.
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.
EudraCT 2019-002317-19, DRKS00019107 . 8th May 2020.
此前一项针对 112 名患者进行的 III 期试验研究了预防性尼莫地平治疗前庭神经鞘瘤（VS）手术中的作用，结果显示尼莫地平治疗并未明显改善面神经和耳蜗神经功能的保留，尽管应该认为保护面神经功能是主要结局。然而，与对照组相比，尼莫地平组术后听力损失风险降低了一半（OR 0.49；95%CI 0.18-1.30；p = 0.15）。因此，这项 III 期扩展试验研究了预防性尼莫地平在 VS 手术中对听力保护的疗效和安全性。
这是一项随机、多中心、双臂、开放标签 III 期试验，采用盲法专家评估和两阶段、中期分析。336 名成人患者有显微手术切除 VS（Koos I-IV）的指征和可手术的术前听力（Gardner-Robertson 量表（GR）1-3），被分配到治疗组（手术前一天开始静脉内尼莫地平 1-2mg/h 至术后第 5 天，以及标准治疗）或对照组（仅手术和标准治疗）。试验的主要终点是根据 GR 1-3 与 GR 4-5（二进制）在出院前评估的术后耳蜗神经功能。听力功能将通过术前和术后言语辨别听力测试来确定，并由盲法专家评估。此外，还将分析使用标准化问卷的患者报告结局。
预防性静脉内尼莫地平治疗可能对 VS 手术中的听力保护有积极影响，并改善患者的生活质量。进一步的次要分析正在计划中。除了剂量依赖性低血压外，尼莫地平是一种已知的安全药物。在未来，预防性尼莫地平治疗可能被推荐为 VS 手术中的常规药物。VS 可以被认为是神经保护临床评估的理想模型，因为听力结果可以通过公认的标准进行分类。尼莫地平的有益作用可能转移到其他有风险的神经的手术中，并可能对基础研究产生影响。
EudraCT 2019-002317-19，DRKS00019107 。2020 年 5 月 8 日。
