ChiCTR2400092043 版本V1.0 版本创建时间2024/11/07 22:03:48 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2400092043 

最近更新日期：

Date of Last Refreshed on：

2024-11-07 22:03:30 

注册时间：

Date of Registration：

2024-11-07 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

儿童癫痫术后抗癫痫发作药物减/停药时间点与癫痫发作预后的关系

Public title：

Relationship between the time point of reducing/stopping antiepileptic drugs after epilepsy surgery in children and the prognosis of epilepsy

注册题目简写：

English Acronym：

研究课题的正式科学名称：

儿童癫痫术后抗癫痫发作药物减/停药时间点与癫痫发作预后的关系

Scientific title：

Relationship between the time point of reducing/stopping antiepileptic drugs after epilepsy surgery in children and the prognosis of epilepsy

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

李栋梁 

研究负责人：

季涛云 

Applicant：

Dongliang Li 

Study leader：

Taoyun Ji 

申请注册联系人电话：

Applicant telephone：

+86 176 3984 3553

研究负责人电话：

Study leader's telephone：

+86 138 1149 2088

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

17639843553@163.com

研究负责人电子邮件：

Study leader's E-mail：

jitaoyun@163.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

北京市大兴区乐园路5号北京大学第一医院

研究负责人通讯地址：

北京市大兴区乐园路5号北京大学第一医院

Applicant address：

Peking University First Hospital, No.5 Leyuan Road, Daxing District, Beijing

Study leader's address：

Peking University First Hospital, No.5 Leyuan Road, Daxing District, Beijing

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

北京大学第一医院

Applicant's institution：

Peking University First Hospital

研究负责人所在单位：

北京大学第一医院

Affiliation of the Leader：

Peking University First Hospital

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

2022研269-002

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

北京大学第一医院生物医学研究伦理委员会

Name of the ethic committee：

Peking University First Hospital Human Research Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

2022-07-28 00:00:00

伦理委员会联系人：

汪科

Contact Name of the ethic committee：

Ke Wang

伦理委员会联系地址：

北京市西城区西什库大街74号

Contact Address of the ethic committee：

No.74 Xishiku Street, Xicheng District, Beijing

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 66119025

伦理委员会联系人邮箱：

Contact email of the ethic committee：

bdyyll@126.com

研究实施负责（组长）单位：

北京大学第一医院

Primary sponsor：

Peking University First Hospital

研究实施负责（组长）单位地址：

北京市大兴区乐园路5号

Primary sponsor's address：

No.5 Leyuan Road, Daxing District, Beijing

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

北京

市(区县)：

Country：

China

Province：

Beijing

City：

单位(医院)：

北京大学第一医院

具体地址：

北京市大兴区乐园路5号

Institution
hospital：

Peking University First Hospital

Address：

No.5 Leyuan Road, Daxing District, Beijing

经费或物资来源：

北京大学第一医院国内多中心临床研究专项

Source(s) of funding：

Peking University First Hospital Domestic Multicenter Clinical Research Project

Target disease：

Drug-refractory epilepsy

Target disease code：

研究类型：

预后研究

Study type：

Prognosis study

研究所处阶段：

 其它 

Study phase：

N/A

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

随着癫痫外科的发展，癫痫手术是药物难治性癫痫的公认治疗选择，但术后无发作病人何时可以减 ASM、何时可以停 ASM，仍是目前癫痫术后管理最具有挑战性的问题。Andermann 等人建议不要在术后一年内更换 ASM，并考虑在手术后两到三年停药。 Kuzniecky 等将接受手术治疗颞叶癫痫病人（共 40例）分为两组，一组术后 4~6 个月内继续维持术前多种 ASM 治疗，另一组术后立即将手术前的多种 ASM 转换为单药（卡马西平）治疗。评估术后第一年内各方案的疗效和安全性，在癫痫发作复发率、复发类型和复发时间方面，两组间没有显着差异。在加拿大癫痫病学家中进行的一项调查显示，约 50%的医生术后 一年不调整 ASM，10% 的医生会 至少两年无发作 才开始减量ASM。在美国的研究也显示了类似的结果。一项荟萃分析发现，在术后无发作病人中的 ASM 调整中，多数医生采取“保守的行为”，开始 ASM 撤药的平均时间为 14 个月（ 3~32 个月）。目前仍然缺少科学、合理的研究指导术后无发作患者的 ASM 的管理。考虑到长期应用 ASM 不良反应、ASM 对认知副作用、经济成本、长期口服 ASM 的心理负担等，癫痫术后无癫痫发作的患者是否可以较早减/停 ASM 是目前亟须解决的问题。故本研究国内多中心研究（北京大学第一医院、清华大学玉泉医院，北京三博脑科医院，山东大学儿童医院，中南大学湘雅医院，郑州大学第一附属医院），纳入癫痫术后无发作的患者开展前瞻性随机对照研究，以建立科学的、有依据术后 ASM 减/停时间节点，并确定与 ASM 减/停时间节点相关的癫痫发作预后影响因素。  

Objectives of Study：

With the development of epilepsy surgery, epilepsy surgery is recognized as the treatment choice for drug-resistant epilepsy. However, when can ASM be reduced and stopped for patients without seizures after surgery is still the most challenging problem in postoperative management of epilepsy. Andermann and others suggested that ASM should not be replaced within one year after operation, and should be stopped two to three years after operation. Kuzniecky et al. divided 40 patients with temporal lobe epilepsy who underwent surgery into two groups. One group continued to maintain various ASM treatments before operation for 4~6 months after operation, and the other group immediately converted various ASM treatments before operation into single drug (carbamazepine) after operation. The efficacy and safety of each scheme in the first year after operation were evaluated. There was no significant difference in the recurrence rate, recurrence type and recurrence time between the two groups. A survey among Canadian epileptics shows that about 50% doctors do not adjust ASM for one year after operation, and 10% doctors will start to reduce ASM after at least two years without seizures. Studies in the United States have also shown similar results. A meta-analysis found that most doctors adopted "conservative behavior" in ASM adjustment in patients without postoperative seizures, and the average time to start ASM withdrawal was 14 months (3~32 months). At present, there is still a lack of scientific and reasonable research to guide the management of ASM in postoperative patients without seizures. Considering the adverse reactions of long-term use of ASM, cognitive side effects of ASM, economic cost and psychological burden of long-term oral administration of ASM, it is an urgent problem to be solved whether patients without epilepsy after epilepsy can reduce/stop ASM earlier. Therefore, in this study, domestic multi-center studies (Peking University First Hospital, Tsinghua University yuquan hospital, Beijing Sanbo Brain Hospital, Children's Hospital of Shandong University, Xiangya Hospital of Central South University, and the First Affiliated Hospital of Zhengzhou University) included patients who had no seizures after operation to carry out prospective randomized controlled studies, so as to establish scientific and well-founded postoperative ASM reduction/stop time nodes and determine the influencing factors of epilepsy prognosis related to ASM reduction/stop time nodes.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

（1）手术年龄≤12岁； （2）术前口服≥2种ASM； （3）癫痫术后两周无发作； （4）病变位于一侧，术后MRI显示病变结构完整切除/离断或致痫区完全切除/隔离； （5）术后7-14天24小时头皮脑电图符合以下标准：无持续的、与病变侧（离断性手术除外）一致的、节律性的癫痫样放电或慢波（局部节律性癫痫样放电或慢波，局部持续性癫痫样放电或慢波）。 注：①病变结构完整切除/离断：根据术后头颅MRI，结构异 常区域被完全切除或离断；②致痫灶完全切除/离断：切除后的术中皮层电图没有显示持续的、与病变一致的、节律性癫痫样放电

Inclusion criteria

(1) The operative age is <=12 years old; (2) Oral administration of >=2 kinds of ASM; before operation; (3) There was no seizure within two weeks after epilepsy operation; (4) The lesion is located on one side, and MRI after operation shows that the lesion structure is completely removed/severed or the epileptogenic zone is completely removed/Isolation; (5) 24-hour scalp EEG after 7-14 days meets the following criteria: no persistent, disconnected from the diseased side. Except for sexual surgery) consistent and rhythmic epileptiform discharge or slow wave (local rhythmic epileptiform discharge or Slow wave, local persistent epileptiform discharge or slow wave). Note: 1) Complete resection/amputation of diseased structures: According to postoperative MRI of the head, abnormal areas of structures were completely excised or amputated; 2) Complete excision/disconnection of epileptogenic focus: The intraoperative electrocorticogram after excision did not show continuous and rhythmic epileptiform discharge consistent with the lesion.

排除标准：

（1）手术时年龄大于12岁； （2）术前口服≤1种ASM； （3）癫痫术后两周内有发作； （4）头颅MRI提示双侧病变； （5）病变位于功能区，因功能保护，结构性病变或致痫区切除/离断不彻底； （6）术后头颅MRI显示病变切除/离断不彻底； （7）术中脑电图监测显示致痫区切除/离断不彻底； （8）术后7-14天24小时头皮脑电图有持续的、与病变侧一致的、节律性的癫痫样放电或慢波（局部节律性癫痫样放电或慢波，局部持续性癫痫样放电或慢波。

Exclusion criteria：

(1) The patient is over 12 years old at the time of operation; (2) Oral administration of <=1 ASM; before operation; (3) Epilepsy occurred within two weeks after operation; (4) Brain MRI showed bilateral lesions; (5) The lesion is located in the functional area, and the excision/disconnection of the structural lesion or epileptogenic area is incomplete due to functional protection; (6) Postoperative MRI showed that the lesion was not completely resected/severed; (7) Intraoperative EEG monitoring showed that the epileptogenic zone was not completely excised/severed; (8) There were persistent, rhythmic epileptiform discharges or slow waves (local rhythmic epileptiform discharges or slow waves, local persistent epileptiform discharges or slow waves) in scalp EEG 24 hours after operation 7-14 days.

研究实施时间：

Study execute time：

从 From 2022-07-28 00:00:00至 To 2025-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2022-08-01 00:00:00 至 To 2023-06-30 00:00:00  

干预措施：

Interventions：

组别：

组1（早减药组）

样本量：

50

Group：

Group 1 (early reduction group)

Sample size：

干预措施：

术后减抗癫痫发作药物（术后3、6、12个月无发作，每三个月减停一种抗癫痫发作药物）

干预措施代码：

Intervention：

Antiepileptic drugs were reduced after operation (no seizures occurred at 3, 6 and 12 months after operation, and one antiepileptic drug was stopped every three months)

Intervention code：

组别：

组2（晚减药组）

样本量：

50

Group：

Group 2(late early reduction group)

Sample size：

干预措施：

术后减抗癫痫发作药物（术后12、18、24个月无发作，每三个月减停一种抗癫痫发作药物）

干预措施代码：

Intervention：

Antiepileptic drugs were reduced after operation (there was no seizure at 12, 18 and 24 months after operation, and one antiepileptic drug was stopped every three months)

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 北京 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

北京大学第一医院 

单位级别：

三甲 

Institution
hospital：

Peking University First Hospital

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 北京 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

清华大学玉泉医院 

单位级别：

三甲 

Institution
hospital：

Yuquan hospital, Tsinghua University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 北京 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

北京三博脑科医院 

单位级别：

三甲 

Institution
hospital：

Beijing Sanbo Brain Hospital

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 湖南 

市(区县)：

 长沙 

Country：

China 

Province：

Hunan 

City：

Changsha 

单位(医院)：

中南大学湘雅医院 

单位级别：

三甲 

Institution
hospital：

xiangya hospital centralsouth university

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 山东 

市(区县)：

 济南 

Country：

China 

Province：

Shangdong 

City：

Jinan 

单位(医院)：

山东大学儿童医院 

单位级别：

三甲 

Institution
hospital：

Children's Hospital of Shandong University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 河南 

市(区县)：

 郑州 

Country：

China 

Province：

Henan 

City：

Zhengzhou 

单位(医院)：

郑州大学第一附属医院 

单位级别：

三甲 

Institution
hospital：

First affiliated hospital of Zhengzhou university

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

随访1年两组无发作率的比较

指标类型：

主要指标

Outcome：

Comparison of seizure-free rate between the two groups after one-year follow-up

Type：

Primary indicator

测量时间点：

筛选期（术前 1 周 - 术后 2 周）、随访期（第3、6、12、18、24、30个月）

测量方法：

监护人记录患儿发作情况。研究者通过电话、门诊随访的形式随访癫痫患儿发作的频率。

Measure time point of outcome：

Screening period (1 week before operation to 2 weeks after operation) and follow-up period (3, 6, 12, 18, 24 and 30 months)

Measure method：

The guardian recorded the seizure of the child. The researchers followed up the frequency of seizures in children with epilepsy by telephone and outpatient follow-up.

指标中文名：

发育商/智商的变化情况

指标类型：

次要指标

Outcome：

Changes of developmental quotient/IQ

Type：

Secondary indicator

测量时间点：

筛选期（术前 1 周 - 术后 2 周）、随访期（第12、24个月）

测量方法：

患者来院进行发育评估

Measure time point of outcome：

Screening period (1 week before operation to 2 weeks after operation) and follow-up period (12th and 24th months).

Measure method：

Patients come to the hospital for developmental assessment.

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

不涉及

组织：

Sample Name：

Not involved

Tissue：

人体标本去向

 其它  

说明

Fate of sample：

0thers  

Note：

征募研究对象情况：

Recruiting status：

结束

/Completed

年龄范围：

Participant age：
最小 Min age 1 岁 years
最大 Max age 12 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

采用分层区组随机的方法，在本研究实施癫痫手术病人的病因中主要分为两大类先天性病因和后天获得性病因，先天性病因主要是脑发育畸形（局灶皮层发育不良、巨脑谱系、灰质移位、多微小脑回等），发育性肿瘤（胚胎发育不良性神经上皮肿瘤、节细胞胶质瘤等）；后天获得性病因主要包括围产期脑损伤、脑卒中、脑出血、低血糖脑损伤、脑炎、脑外伤等。获得性病因常常受累范围广，癫痫术后复发率高。因病因对于手术后的预后影响较大，为了达到早减药组和晚减药组病因分配的平衡，减少偏倚。故本研究术后病人按照先天性病因和后天获得性病因分为两层，之后每组病因采用信封法进行分配隐藏，随机分为早减药组和晚减药组我们采用的随机方法是“信封法”，为了保证随机分组正确无误，我们会邀请专业人员根据我们的试验要求设计和制作随机信封。分组方案装入一个不透光的信封中，信封中隐藏随机分组的信息，信封外面写上编码。随机分组信封制作好后，将信封后交给负责的研究者，若符合入选标准，给病人编号，再打开相应编号的信封，按信封内的分组方案进行。随机序列由随机数字表生成。

Randomization Procedure (please state who generates the random number sequence and by what method)：

Using stratified block random method, the causes of patients undergoing epilepsy surgery in this study are mainly divided into two categories: congenital causes and acquired causes. The congenital causes are mainly brain dysplasia (focal cortical dysplasia, giant brain pedigree, gray matter displacement, multiple tiny gyrus, etc.) and developmental tumors (neuroepithelial tumors with poor embryonic development, gangliogliomas, etc.). Acquired causes mainly include perinatal brain injury, stroke, cerebral hemorrhage, hypoglycemia brain injury, encephalitis, brain injury and so on. Acquired etiology often involves a wide range, and the recurrence rate of epilepsy after operation is high. Because the etiology has a great influence on the prognosis after operation, in order to achieve the balance of etiology distribution between the early drug reduction group and the late drug reduction group and reduce bias. Therefore, the postoperative patients in this study are divided into two layers according to congenital etiology and acquired etiology, and then each group of etiology is distributed and hidden by envelope method, and randomly divided into early drug reduction group and late drug reduction group. Our random method is "envelope method". In order to ensure the correctness of random grouping, we will invite professionals to design and make random envelopes according to our experimental requirements. The grouping scheme is put into an opaque envelope, in which the information of random grouping is hidden and the code is written on the outside of the envelope. After the envelopes are randomly grouped, they will be handed over to the responsible researcher. If they meet the selection criteria, the patients will be numbered, and then the envelopes with corresponding numbers will be opened according to the grouping scheme in the envelopes.Random sequence is generated by random number table.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

开放标签

Blinding：

Open label

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

Yes

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

邮件索取，预计共享原始数据的时间是2026年6月

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

request by email,It is estimated that the original data will be shared in June 2026.

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

通过病例记录表CRF表进行数据采集，通过EXCEL表格进行数据管理

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Data were collected through the CRF, and data were managed through EXCEL table

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2024-11-07 22:03:30