ChiCTR2400094046 版本V1.0 版本创建时间2024/12/16 17:01:37 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：

 ChiCTR2400094046 

最近更新日期：

Date of Last Refreshed on：

 2024-12-16 17:00:13 

注册时间：

Date of Registration：

 2024-12-16 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

硬膜外连续输注羟乙基淀粉治疗自发性低颅压综合征的临床疗效和影像学变化

Public title：

The Clinical efficacy and imaging changes after continuous epidural infusion of Hetastarch for treatment of spontaneous intracranial hypotension

注册题目简写：

English Acronym：

研究课题的正式科学名称：

硬膜外连续输注羟乙基淀粉治疗自发性低颅压综合征的临床疗效和影像学变化

Scientific title：

The Clinical efficacy and imaging changes after continuous epidural infusion of Hetastarch for treatment of spontaneous intracranial hypotension

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：

李世超 

研究负责人：

缪长虹 

Applicant：

Shichao Li 

Study leader：

Changhong Miao 

申请注册联系人电话：

Applicant telephone：

 +86 136 3663 0566

研究负责人电话：

Study leader's
telephone：

+86 136 8197 5062

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：

 Li.shichao@zs-hospital.sh.cn

研究负责人电子邮件：

Study leader's E-mail：

 Miao.changhong@zs-hospital.sh.cn

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：

上海市枫林路180号

研究负责人通讯地址：

上海市枫林路180号

Applicant address：

180 Fenglin Road, Shanghai

Study leader's address：

180 Fenglin Road, Shanghai

申请注册联系人邮政编码：

Applicant postcode：

 200032

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

复旦大学附属中山医院

Applicant's institution：

Zhongshan Hospital, Fudan University

研究负责人所在单位：

复旦大学附属中山医院

Affiliation of the Leader：

Zhongshan Hospital, Fudan University

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 B2023-050

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：

复旦大学附属中山医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Zhongshan Hospital, Fudan University

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-03-13 00:00:00

伦理委员会联系人：

陈千晴

Contact Name of the ethic committee：

Qianqing Chen

伦理委员会联系地址：

上海市枫林路180号

Contact Address of the ethic committee：

180 Fenglin Road, Shanghai

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 21 3158 7871

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

复旦大学附属中山医院

Primary sponsor：

Zhongshan Hospital, Fudan University

研究实施负责（组长）单位地址：

上海市枫林路180号

Primary sponsor's address：

180 Fenglin Road, Shanghai

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中华人民共和国

省(直辖市)：

上海

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

复旦大学附属中山医院

具体地址：

上海市枫林路180号

Institution
hospital：

Zhongshan Hospital, Fudan University

Address：

180 Fenglin Road, Shanghai

经费或物资来源：

NO: 2020–112：上海市领军人才项目

Source(s) of funding：

NO: 2020–112: Shanghai Leading Talents Program

研究疾病：

自发性低颅压综合征  

Target disease：

spontaneous intracranial hypotension

研究疾病代码：

8D61.0

Target disease code：

8D61.0

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 探索性研究/预试验 

Study phase：

0

研究设计：

单臂 

Study design：

Single arm 

研究目的：

1.评估硬膜外连续输注羟乙基淀粉治疗自发性低颅压综合征的临床疗效 2.比较自发性低颅压综合征患者在接受硬膜外连续输注羟乙基淀粉治疗前后的头颅MRI和脊髓MRI水成像的影像学变化  

Objectives of Study：

1. Evaluate the clinical efficacy of continuous epidural infusion of hydroxyethyl starch in the treatment of spontaneous hypotension syndrome; 2. Compare the imaging changes of head MRI and spinal cord MRI hydrography in patients with spontaneous hypotension syndrome before and after continuous epidural infusion of hydroxyethyl starch treatment.

药物成份或治疗方案详述：

药物：羟乙基淀粉130/0.4氯化钠注射液 生产商：德国费森尤斯卡比股份有限公司 治疗方案：硬膜外穿刺置管，通过输液泵连续输注羟乙基淀粉注射液2-3天 

Description for medicine or protocol of treatment in detail：

Drug: Hydroxyethyl Starch 130/0.4 and Sodium Chloride Injection,HES; Manufacturer: Fresenius Kabi Deutschland GmbH, Germany; Treatment plan: Epidural puncture and catheterization, continuous infusion of hydroxyethyl starch injection through an infusion pump for 2-3 days. 

纳入标准：

1） 年龄不小于18周岁，符合第3版国际头痛疾病分类（International Classification of Headache Disorders, 3rd edition, ICHD-3）标准诊断自发性低颅压综合征： a) 任何符合以下标准c的头痛； b) 脑脊液压力降低（<60mmH2O）和/或影像学检查显示脑脊液漏； c) 头痛的发生与低脑脊液压力或脑脊液漏存在时间相关性，或由于头痛而发现了低脑脊液压力或脑脊液漏的存在；如脑脊液漏点位置未知，定位下胸段进行穿刺 d) 患者的表现不能用ICHD-3中的其他疾病来更好地解释。 2） 保守治疗（卧床休息、水化、镇痛治疗等）2周失败（仍存在体位性头痛等临床症状且影像学提示仍有硬膜外脑脊液积聚）。 3） 向患者详细告知硬膜外连续注射HES与EBP治疗相比的优、缺点和并发症后获得患者及家属知情同意。

Inclusion criteria

1. Age >=18, Diagnosis of spontaneous intracranial hypotension according to the International Classification of Headache Disorders, 3rd edition, ICHD-3: a) Any headache that meets the following criterion c; b) Reduced cerebrospinal fluid (CSF) pressure (<60mmH2O) and/or imaging studies show CSF leakage; c) The onset of headache is temporally related to low CSF pressure or CSF leakage, or the presence of low CSF pressure or CSF leakage is discovered due to headache; if the site of CSF leakage is unknown, perform puncture at the lower thoracic level; d) The patient's presentation cannot be better explained by other disorders in the ICHD-3. 2. Conservative treatment (bed rest, hydration, analgesic treatment, etc.) failed for 2 weeks (clinical symptoms such as postural headache still exist and imaging suggests accumulation of epidural cerebrospinal fluid); 3. Provide patients with detailed information on the advantages, disadvantages, and complications of continuous epidural injection of HES compared to EBP treatment, and obtain informed consent from patients and their families.

排除标准：

1) 患者拒绝参与研究； 2) 患者不能配合手术操作或穿刺部位存在感染； 3) 凝血功能异常（如低凝状态、血小板降低、或抗凝药物未停药等）； 4) 肝、肾功能不全，血清总胆红素＞1.5倍正常值上限（ULN）；肝转移患者＞2.5倍ULN，谷草转氨酶（AST）及谷丙转氨酶（ALT）＞2.5倍ULN，或伴肝转移患者ALT和/或AST＞5倍ULN，血清肌酐＞1.5倍正常值上限（ULN），或肌酐清除率<50ml/min（根据Cockcroft-Gault公式计算）。 5) 入选前6个月内有动脉血栓或深静脉血栓史，或入组前2个月内具有出血倾向证据或病史的患者，无论严重程度如何。 6) 皮肤伤口、手术部位、创伤部位、粘膜严重溃疡或骨折没有完全愈合。 7) 已证实对试验药物和/或其辅料过敏。 8) 怀孕或哺乳期妇女。 9) 严重慢性或活动性感染，需要进行全身抗菌、抗真菌或抗病毒治疗，包括急性肝炎、结核病感染等。在筛选前≥1年曾有活动性结核感染病史的患者也应排除在外，除非可以提供证明表明已经完成适当的治疗。 10) 临床显著的胸腔积液、心包积液或腹水，需要在研究药物首次给药前2周内多次进行引流。 11) 已知有人体免疫缺陷病毒感染病史。 12) 研究者认为受试者存在任何临床或实验室异常或依从性问题而不适宜参加本临床研究。 13) 存在严重的心理或精神异常。 14) 在首次研究药物给药前≤28天进行过任何大型外科手术。

Exclusion criteria：

1.The patient refuses to participate in the study; 2.The patient can not cooperate with surgical procedures or there is an infection at the puncture site; 3.Coagulation dysfunction (such as hypocoagulability, thrombocytopenia, or not discontinuing anticoagulant medication, etc.); 4.Hepatic or renal insufficiency, with serum total bilirubin >1.5 times the upper limit of normal (ULN); for patients with liver metastasis >2.5 times ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5 times ULN, or for patients with liver metastasis, ALT and/or AST >5 times ULN, serum creatinine >1.5 times the upper limit of normal (ULN), or creatinine clearance <50 ml/min (calculated according to the Cockcroft-Gault formula); 5.History of arterial thrombosis or deep vein thrombosis within 6 months prior to enrollment, or evidence or history of bleeding tendency within 2 months prior to enrollment, regardless of severity; 6.Skin wounds, surgical sites, trauma sites, severe mucosal ulcers, or fractures that have not completely healed; 7.Proven allergy to the test medication and/or its excipients; 8.Pregnant or breastfeeding women; 9.Severe chronic or active infections requiring systemic antimicrobial, antifungal, or antiviral treatment, including acute hepatitis, tuberculosis infections, etc. Patients with a history of active tuberculosis infection >=1 year before screening should also be excluded unless proof can be provided that appropriate treatment has been completed; 10.Clinically significant pleural effusion, pericardial effusion, or ascites requiring multiple drainages within 2 weeks prior to the first administration of the study drug; 11.Known history of human immunodeficiency virus infection; 12.The investigator believes that the subject has any clinical or laboratory abnormalities or compliance issues that make them unsuitable for participation in this clinical study; 13.Presence of severe psychological or mental abnormalities; 14Any major surgical procedure within <=28 days prior to the first administration of the study drug.

研究实施时间：

Study execute time：

从 From 2025-01-01 00:00:00至 To 2026-03-10 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-01-01 00:00:00 至 To 2026-02-28 00:00:00

干预措施：

Interventions：

组别：

治疗组

样本量：

 32

Group：

Therapy group

Sample size：

干预措施：

硬膜外穿刺置管，通过输液泵连续输注羟乙基淀粉注射液2-3天

干预措施代码：

Intervention：

Epidural puncture and catheterization, continuous infusion of hydroxyethyl starch injection through an infusion pump for 2-3 days

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中华人民共和国

省(直辖市)：

 上海 

市(区县)：

  

Country：

China

Province：

Shanghai

City：

单位(医院)：

 复旦大学附属中山医院 

单位级别：

 三甲 

Institution
hospital：

Zhongshan Hospital, Fudan University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

初次治疗成功率

指标类型：

主要指标

Outcome：

Success rate for first treatment

Type：

Primary indicator

测量时间点：

术后

测量方法：

头颅MR和脊髓MR

Measure time point of outcome：

after surgery

Measure method：

MR of head and spine

指标中文名：

临床症状

指标类型：

次要指标

Outcome：

clinical symptoms

Type：

Secondary indicator

测量时间点：

术前、术后即刻、术后4h、8h、12h、24h、36h、48h、72h、术后一周、术后一月、术后二月、术后三月、术后六月

测量方法：

主观描述

Measure time point of outcome：

Preoperatively, immediately postoperative, 4 hours postoperative, 8 hours postoperative, 12 hours postoperative, 24 hours postoperative, 36 hours postoperative, 48 hours postoperative, 72 hours postoperative, one week postoperative, one month postoperative, two months postoperative, three months postoperative, six months postoperative

Measure method：

Patient's subjective description

指标中文名：

体位性头痛的VAS评分

指标类型：

次要指标

Outcome：

VAS score for positional headache

Type：

Secondary indicator

测量时间点：

术前、术后即刻、术后4h、8h、12h、24h、36h、48h、72h、术后一周、术后一月、术后二月、术后三月、术后六月

测量方法：

VAS评分

Measure time point of outcome：

Preoperatively, immediately postoperative, 4 hours postoperative, 8 hours postoperative, 12 hours postoperative, 24 hours postoperative, 36 hours postoperative, 48 hours postoperative, 72 hours postoperative, one week postoperative, one month postoperative, two months postoperative, three months postoperative, six months postoperative

Measure method：

VAS score

指标中文名：

所有相关术后短期及长期并发症

指标类型：

次要指标

Outcome：

All related short-term and long-term postoperative complications

Type：

Secondary indicator

测量时间点：

术前、术后即刻、术后4h、8h、12h、24h、36h、48h、72h、术后一周、术后一月、术后二月、术后三月、术后六月

测量方法：

主观描述

Measure time point of outcome：

Preoperatively, immediately postoperative, 4 hours postoperative, 8 hours postoperative, 12 hours postoperative, 24 hours postoperative, 36 hours postoperative, 48 hours postoperative, 72 hours postoperative, one week postoperative, one month postoperative, two months postoperative, three months postoperative, six months postoperative

Measure method：

Patient's subjective description

指标中文名：

直立后严重头痛发作的时间

指标类型：

次要指标

Outcome：

The timing of severe headache episodes after standing upright

Type：

Secondary indicator

测量时间点：

术前、术后即刻、术后4h、8h、12h、24h、36h、48h、72h、术后一周、术后一月、术后二月、术后三月、术后六月

测量方法：

Measure time point of outcome：

Preoperatively, immediately postoperative, 4 hours postoperative, 8 hours postoperative, 12 hours postoperative, 24 hours postoperative, 36 hours postoperative, 48 hours postoperative, 72 hours postoperative, one week postoperative, one month postoperative, two months postoperative, three months postoperative, six months postoperative

Measure method：

指标中文名：

需要躺下之前能够直立的时间

指标类型：

次要指标

Outcome：

The duration of time able to stand upright before needing to lie down

Type：

Secondary indicator

测量时间点：

术前、术后即刻、术后4h、8h、12h、24h、36h、48h、72h、术后一周、术后一月、术后二月、术后三月、术后六月

测量方法：

Measure time point of outcome：

Preoperatively, immediately postoperative, 4 hours postoperative, 8 hours postoperative, 12 hours postoperative, 24 hours postoperative, 36 hours postoperative, 48 hours postoperative, 72 hours postoperative, one week postoperative, one month postoperative, two months postoperative, three months postoperative, six months postoperative

Measure method：

指标中文名：

每天能够直立的累计小时数

指标类型：

次要指标

Outcome：

The cumulative number of hours able to stand upright each day

Type：

Secondary indicator

测量时间点：

术前、术后即刻、术后4h、8h、12h、24h、36h、48h、72h、术后一周、术后一月、术后二月、术后三月、术后六月

测量方法：

Measure time point of outcome：

Preoperatively, immediately postoperative, 4 hours postoperative, 8 hours postoperative, 12 hours postoperative, 24 hours postoperative, 36 hours postoperative, 48 hours postoperative, 72 hours postoperative, one week postoperative, one month postoperative, two months postoperative, three months postoperative, six months postoperative

Measure method：

指标中文名：

生活质量结局评分

指标类型：

附加指标

Outcome：

Quality of life outcome scores

Type：

Additional indicator

测量时间点：

术前、术后即刻、术后4h、8h、12h、24h、36h、48h、72h、术后一周、术后一月、术后二月、术后三月、术后六月

测量方法：

QoR-15

Measure time point of outcome：

Preoperatively, immediately postoperative, 4 hours postoperative, 8 hours postoperative, 12 hours postoperative, 24 hours postoperative, 36 hours postoperative, 48 hours postoperative, 72 hours postoperative, one week postoperative, one month postoperative, two months postoperative, three months postoperative, six months postoperative

Measure method：

Quality of Recovery-15

指标中文名：

头颅MRI检查

指标类型：

次要指标

Outcome：

Cranial MRI examination

Type：

Secondary indicator

测量时间点：

术前、术后一个月、术后二/三月、术后六月

测量方法：

Measure time point of outcome：

Preoperatively, one month postoperative, two to three months postoperative, six months postoperative.

Measure method：

指标中文名：

脊髓MRI水成像检查

指标类型：

次要指标

Outcome：

Spinal MRI with water imaging

Type：

Secondary indicator

测量时间点：

术前、术后一个月、术后二/三月、术后六月

测量方法：

Measure time point of outcome：

Preoperatively, one month postoperative, two to three months postoperative, six months postoperative.

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

无

组织：

Sample Name：

no

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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 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）：

无

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

None

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：

无

Blinding：

None

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

否No

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）：

不共享

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

no sharing

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：

试验采用电子化数据管理，使用Resman(http://www.medresman.org.cn)。以下列出数据管理主要流程，其他详见数据管理计划(DMP)。DMP作为数据管理的指导性文件由数据管理员(DM)撰写，申办方批准，数据管理工作将根据DMP定义的时间、内容及方法进行(http://www.medresman.org.cn)。 EDC数据管理流程 l电子病例报告表(eCRF)：数据管理员根据试验方案设计构建，并根据数据核查计划(DVP)设置逻辑核查，通过测试并获申办方批准后发布使用。 2数据录入：eCRF数据来源于原始记录，由数据录入人员根据eCRF填写说明，将受试者访视数据及时录入EDC。 3源数据现场核查(SDV)：监查员进行eCRF数据与源数据的一致性核对，有问题可发疑问。 4数据疑问和解答：疑问来源于EDC逻辑核查的系统疑问，监查员、数据管理员等人工疑问，研究者需及时解答疑问。数据管理员和监查员进行疑问批复，必要时可再次发出疑问，直至数据“清洁”。 5研究者签名：数据录入完成并经SDV后，研究者进行电子签名审核确认。签名后的如有数据修订，需重新签名。 6数据库锁定：由主要研究者、申办者、统计分析人员和数据管理人员共同签署数据库锁定记录后，数据管理员进行数据库锁定。 7数据库提交：数据管理员向统计人员提交数据库。 8eCRF存档：每个受试者的eCRF生成PDF电子文档保存。 9数据管理报告：由数据管理员撰写。 10EDC关闭：统计分析完成后，数据管理员关闭数据库。

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

The trial adopts electronic data management, using Resman (http://www.medresman.org.cn). Below are the main data management processes, with details referred to the Data Management Plan (DMP). The DMP, as a guiding document for data management, is written by the Data Manager (DM), approved by the sponsor, and data management work will be carried out according to the time, content, and methods defined by the DMP (http://www.medresman.org.cn). EDC Data Management Process: 1. Electronic Case Report Form (eCRF): The Data Manager designs and constructs the eCRF based on the trial protocol and sets up logical checks according to the Data Verification Plan (DVP). After testing and obtaining sponsor approval, it is published for use; 2. Data Entry: eCRF data originates from source documents, and data entry personnel enter subject visit data into the EDC in a timely manner according to the eCRF filling instructions; 3. Source Data Verification (SDV): Monitors conduct consistency checks between eCRF data and source data, and can raise queries if there are issues; 4. Data Queries and Resolutions: Queries originate from system queries generated by EDC logical checks, as well as manual queries from monitors, Data Managers, etc. Investigators need to respond to queries promptly. Data Managers and monitors provide query resolutions, and if necessary, can issue queries again until the data is "clean."; 5. Investigator Signature: After data entry is completed and SDV is conducted, the investigator performs electronic signature review and confirmation. If there are data revisions after signing, a new signature is required; 6. Database Locking: The database is locked by the Data Manager after the principal investigator, sponsor, statistical analyst, and data management personnel jointly sign the database lock record; 7. Database Submission: The Data Manager submits the database to the statistician; 8. eCRF Archiving: Each subject's eCRF is saved as a PDF electronic document; 9. Data Management Report: Written by the Data Manager; 10. EDC Closure: After statistical analysis is completed, the Data Manager closes the database.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2024-12-16 17:00:13