Numen弹簧圈治疗未破裂颅内动脉瘤的安全性和有效性分析:CATCH试验的亚组分析

Safety and efficacy analysis of Numen coil in the treatment of unruptured intracranial aneurysms:a subgroup analysis of the CATCH trial

目的探讨国产Numen弹簧圈治疗未破裂颅内动脉瘤的安全性和有效性。方法2017年4月至2019年2月海军军医大学第一附属医院等10家临床试验中心共同完成前瞻性、多中心、开放性、随机对照、非劣效性临床试验——CATCH试验,纳入其中240例未破裂颅内动脉瘤亚组进行分析;根据术中使用的弹簧圈类型将患者分为Numen组与Axium组。主要有效性观察指标为术后6个月动脉瘤的成功闭塞率(Raymond分级为Ⅰ或Ⅱ级);次要有效性指标为术后6个月、12个月的动脉瘤完全闭塞率(Raymond分级为Ⅰ级)以及术后6个月的动脉瘤再通率。安全性指标为术后6个月、12个月的动脉瘤再治疗率和严重不良事件的发生率。结果全分析集中,与Axium组(117例)比较,Numen组(123例)原发性高血压患者占比低(P=0.030),而性别、年龄等基线资料的差异均无统计学意义(均P>0.05)。符合方案集(Numen组103例,Axium组98例)中,两组术后6个月动脉瘤成功闭塞率[93.2%(96/103)对比95.9%(94/98)]、完全闭塞率[65.0%(67/103)对比63.3%(62/98)]以及再通率[5.9%(6/101)对比2.1%(2/97)]的差异均无统计学意义(均P>0.05);术后12个月动脉瘤完全闭塞率的差异无统计学意义[均为74.4%(67/90),χ^(2)=0.00,P=1.000];术后即刻动脉瘤栓塞密度的差异无统计学意义[(41.90±22.32)%对比(45.72±19.51)%,t=-1.30,P=0.198]。全分析集中,两组患者有效性指标的差异亦均无统计学意义(均P>0.05)。安全性分析集(Numen组123例,Axium组117例)中,术后12个月,Axium组患者中1例接受再治疗(1/112,0.9%),116例Numen组患者中无一例接受再治疗,两组间差异无统计学意义(P=0.491);截至术后12个月,Numen组与Axium组严重不良事件发生率的差异无统计学意义[13.0%(16/123)对比17.9%(21/117),χ^(2)=1.18,P=0.289];两组患者的病死率均为0。结论Numen弹簧圈与Axium弹簧圈治疗未破裂颅内动脉瘤的安全性和有效性相近,是一种安全、有效的治疗选择。

Objective To evaluate the safety and efficacy of domestic Numen coil in the treatment of intracranial unruptured aneurysms.Methods A prospective,multicenter,open,randomized controlled,non-inferiority clinical trial-CATCH trial was completed jointly by 10 clinical trial centers,including the First Affiliated Hospital of Naval Medical University,from April 2017 to February 2019,in which a subgroup of 240 cases of unruptured intracranial aneurysms was included for analysis.The patients were classified into the Numen group and Axium group.The primary outcome was the rate of successful occlusion of the aneurysm(Raymond grade Ⅰ or Ⅱ)at 6 months postoperatively.The secondary outcomes included the rate of complete occlusion of the aneurysm(Raymond grade Ⅰ)at 6 and 12 months postoperatively and the rate of recanalization of aneurysm at 6 months postoperatively.The safety indicators were aneurysm retreatment rate at 6 and 12 months postoperatively and the rate of serious adverse events.Results In the full analysis set,the Numen group(123 patients)had a lower percentage of patients with essential hypertension compared with the Axium group(117 patients)(P=0.030),whereas the differences in baseline data such as gender and age were not statistically significant(all P>0.05).In the per-protocal set,the rates of successful aneurysm occlusion[93.2%(96/103)vs.95.9%(94/98)],complete occlusion[65.0%(67/103)vs.63.3%(62/98)],and recanalization[5.9%(6/101)vs.2.1%(2/97)]at 6 months postoperatively were not statistically significant between the two groups(all P>0.05).The difference in the rate of complete occlusion of the aneurysm at 12 months postoperatively was not statistically significant[both of them were 74.4%(67/90),χ^(2)=0.00,P=1.000].There was no statistically significant difference in the immediate postoperative packing density[(41.90±22.32)%vs.(45.72±19.51)%,t=-1.30,P=0.198].In the full analysis set,none of the differences in effectiveness indicators between the two groups was significant(P>0.05).In the safety analysis set(123 patients in the Numen group and 117 patients in the Axium group),at 12 months postoperatively,i patient in the Axium group was retreated(1/112,0.9%),none of the 116 patients in the Numen group was retreated,and the difference between the two groups was not statistically significant(P=0.491).At 12 months post operation,there was no statistically significant difference in the incidence of serious adverse events between the Numen group and Axium group[13.0%(16/123)vs.17.9%(21/117),χ^(2)=1.18,P=0.289].The mortality rate of patients was 0 in both groups.Conclusion Numen coils demonstrate similar safety and efficacy as Axium coils for the treatment of unruptured intracranial aneurysms and could be used as a safe and effective method.