ChiCTR2300075033 版本V1.0 版本创建时间2023/08/23 15:15:10 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：

 ChiCTR2300075033 

最近更新日期：

Date of Last Refreshed on：

 2023-08-23 15:14:50 

注册时间：

Date of Registration：

 2023-08-23 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

芪蛭通络颗粒干预低风险型原发性膜性肾病的随机、双盲、对照临床试验

Public title：

Randomized, double-blind, controlled clinical trial of Qizhi Tongluo Granules in the intervention of low-risk primary membranous nephropathy

注册题目简写：

English Acronym：

研究课题的正式科学名称：

芪蛭通络颗粒干预低风险型原发性膜性肾病的随机、双盲、对照临床试验

Scientific title：

Randomized, double-blind, controlled clinical trial of Qizhi Tongluo Granules in the intervention of low-risk primary membranous nephropathy

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：

杨凤文 

研究负责人：

檀金川 

Applicant：

Fengwen Yang 

Study leader：

Jinchuan Tan 

申请注册联系人电话：

Applicant telephone：

 +86 139 3186 0877

研究负责人电话：

Study leader's
telephone：

+86 138 3118 7910

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：

 yfwen1021@163.com

研究负责人电子邮件：

Study leader's E-mail：

 1955981973@qq.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：

河北省石家庄市长安区中山东路389号

研究负责人通讯地址：

河北省石家庄市长安区中山东路389号

Applicant address：

389 Zhongshan Dong Lu, Chang 'an District, Shijiazhuang City, Hebei Province, China

Study leader's address：

389 Zhongshan Dong Lu, Chang 'an District, Shijiazhuang City, Hebei Province, China

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：

河北省中医院

Applicant's institution：

Hebei Provincial Hospital of Traditional Chinese Medicine

研究负责人所在单位：

河北省中医院

Affiliation of the Leader：

Hebei Provincial Hospital of Traditional Chinese Medicine

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：

 HBZY2023-KY-020-01

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：

河北省中医院医学伦理委员会

Name of the ethic committee：

Ethics Committee of Hebei Provincial Hospital of Traditional Chinese Medicine

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-07-10 00:00:00

伦理委员会联系人：

胡婧楠

Contact Name of the ethic committee：

Jingnan Hu

伦理委员会联系地址：

河北省石家庄市长安区中山东路389号

Contact Address of the ethic committee：

389 Zhongshan Road East, Chang'an District, Shijiazhuang, Hebei

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 311 6900 5606

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：

河北省中医院

Primary sponsor：

Hebei Provincial Hospital of Traditional Chinese Medicine

研究实施负责（组长）单位地址：

河北省石家庄市长安区中山东路389号

Primary sponsor's address：

389 Zhongshan Dong Lu, Chang 'an District, Shijiazhuang City, Hebei Province, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

河北省

市(区县)：

石家庄市

Country：

China

Province：

Hebei Province

City：

Shijiazhuang City

单位(医院)：

河北省中医院

具体地址：

河北省石家庄市长安区中山东路389号

Institution
hospital：

Hebei Provincial Hospital of Traditional Chinese Medicine

Address：

389 Zhongshan Dong Lu, Chang 'an District, Shijiazhuang City, Hebei Province, China

经费或物资来源：

河北省科技厅重点研发计划项目

Source(s) of funding：

Key research and development project of Hebei Provincial Science and Technology Department

研究疾病：

膜性肾病  

Target disease：

Membranous nephropathy

研究疾病代码：

Target disease code：

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：

随机平行对照 

Study design：

Parallel 

研究目的：

评价芪蛭通络颗粒治疗PMN的临床疗效及安全性，并进一步探讨其治疗机理，为有效治疗及控制疾病的演变提供新途径、新方法、新理论，降低终末期肾病的发生率。  

Objectives of Study：

To evaluate the clinical efficacy and safety of Qizhitongluo granules in the treatment of PMN, and further explore its therapeutic mechanism, so as to provide a new approach, new method and new theory for effective treatment and control of the evolution of the disease, and reduce the incidence of end-stage renal disease.

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）2年内确诊为Ⅰ期－Ⅲ期PMN，肾穿刺病理：肾组织光镜检查时肾小球不少于12个，所有肾组织标本至少行光镜、免疫荧光检查； （2）18-65岁年龄； （3）抗磷脂酶A2受体抗体阳性（间接免疫荧光法IFA）； （4）eGFR正常，24小时尿蛋白定量＜3.5g/24h，和/或血白蛋白大于30g/L； （5）依据指南建议最大剂量或最大耐受量服用稳定剂量的血管紧张素转换酶抑制剂(ACEI)或血管紧张素Ⅱ受体阻滞剂（ARB）、至少8周内保持稳定（剂量变化<25%）； （6）符合中医气虚（包括肺脾气虚证、脾肾气虚证、肺肾两虚证）血瘀证（包括瘀血阻络证、瘀水互结证）分型标准。

Inclusion criteria

(1)He was diagnosed with stage I-III PMN within 2 years. The pathology of renal puncture meets the following requirements: no less than 12 glomeruli should be examined by light microscopy, and all renal tissue specimens should be examined by light microscopy and immunofluorescence at least; (2)18-65 years old; (3)Anti-phospholipase A2 receptor antibody positive (indirect immunofluorescence IFA); (4)eGFR is normal, 24-hour urinary protein volume < 3.5g/24h, and/or blood albumin greater than 30g/L; (5)Take a stable dose of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-ⅱ receptor blocker (ARB) for at least 8 weeks at the maximum or tolerated dose recommended by the guidelines (dose change <25%); (6)It meets the classification standard of Qi deficiency (including lung qi deficiency, spleen kidney qi deficiency, lung and kidney deficiency) and blood stasis syndrome (including blood stasis blocking collaterality syndrome, blood stasis and water interjunction syndrome).

排除标准：

（1）自身免疫性疾病、肿瘤、乙肝、感染及药物等引起的各种继发性MN； （2）艾滋病、乙肝或丙肝病毒阳性者； （3）肝功能异常、白细胞减少或免疫缺陷者； （4）严重消化道疾病、感染、糖尿病、恶性肿瘤及严重心脑血管疾病者； （5）全身出血倾向性疾病如血友病、特发性血小板减少性紫癜； （6）存在严重的、致残的或者威胁生命的与肾病综合征相关的并发症者； （7）正在或计划怀孕及哺乳的患者； （8）近1个月曾接受细胞毒性药物、免疫抑制剂等药物治疗； （9）双肾彩超提示肾动脉狭窄； （10）对动物蛋白过敏者； （11）肾移植患者； （12）研究者认为不能依从研究方案者。

Exclusion criteria：

(1)Patients with various secondary MN caused by autoimmune diseases, tumors, hepatitis B, infections and drugs; (2)HIV/AIDS, hepatitis B or C virus positive; (3)Abnormal liver function, leukopenia or immune deficiency; (4)Patients with severe digestive tract diseases, infections, diabetes, malignant tumors and serious cardiovascular and cerebrovascular diseases; (5)There are systemic bleeding tendency diseases, such as hemophilia, idiopathic thrombocytopenic purpura, etc; (6)There are severe, disabling, or life threatening complications associated with nephrotic syndrome; (7)Patients who are pregnant or planning to breastfeed; (8)Patients who have received cytotoxic drugs, immunosuppressants and other drugs in the past 1 month; (9)Double kidney color ultrasound indicates renal artery stenosis; (10)Allergic to animal protein; (11)Kidney transplant patient; (12)Those who the researcher considers unable to comply with the study protocol.

研究实施时间：

Study execute time：

从 From 2023-08-01 00:00:00至 To 2026-02-28 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-09-01 00:00:00 至 To 2025-08-31 00:00:00

干预措施：

Interventions：

组别：

观察组

样本量：

 30

Group：

Observation group

Sample size：

干预措施：

芪蛭通络颗粒口服

干预措施代码：

Intervention：

Qizhi Tongluo granules for oral administration

Intervention code：

组别：

对照组

样本量：

 30

Group：

Control group

Sample size：

干预措施：

芪蛭通络颗粒模拟剂口服

干预措施代码：

Intervention：

Qizhi Tongluo granule simulation agent for oral administration

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 河北省 

市(区县)：

 石家庄市 

Country：

China

Province：

Hebei Province

City：

Shijiazhuang City

单位(医院)：

 河北省中医院 

单位级别：

 三级甲等 

Institution
hospital：

Hebei Provincial Hospital of Traditional Chinese Medicine

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

治疗24周时MN的完全缓解及部分缓解

指标类型：

主要指标

Outcome：

Complete and partial remission of MN at 24 weeks of treatment

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

治疗4周、12周及24周时与基线相比eGFR的变化

指标类型：

次要指标

Outcome：

Changes in eGFR compared to baseline at 4, 12, and 24 weeks of treatment

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

完全及部分缓解的中位时间

指标类型：

次要指标

Outcome：

Median time of complete and partial remission

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

用EQ-5D问卷进行评估的的健康相关生活质量

指标类型：

次要指标

Outcome：

Health related quality of life evaluated using the EQ-5D questionnaire

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

中医证候积分

指标类型：

次要指标

Outcome：

Traditional Chinese Medicine Syndrome Points

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

尿液

组织：

Sample Name：

urine

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

标本中文名：

血清

组织：

Sample Name：

serum

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

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 65 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SPSS随机数字生成器分为治疗组和对照组

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

SPSS

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：

双盲

Blinding：

Double blind

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）：

http://test.empoweredc.com/login

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

http://test.empoweredc.com/login

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：

为提高研究质量，减少研究偏倚，研究过程中将实时进行受试者数据实时录入，第三方数据管理、第三方盲态统计分析等工作，第三方进行数据分析，并出具统计分析报告。 1.数据管理 要求如下： （1）研究员根据受试者实际情况进行原始数据观察，记录CRF表。研究员需保证数据真实、完整、准确。所有项目均需填写，不得空项、漏项，做任何更正时只能划线，旁注修改后的内容，由调查员签名并注明日期，不得涂擦、覆盖原始记录。 （2）数据录入与管理由专人负责。编写相应的计算机程序，采用独立双份录入方式进行数据录入。数据管理员对数据进行核查，发现的疑问及时向调查员进行询问、核对，数据管理员根据调查员的回答进行数据确认、修改。错误内容及修改结果应如实记录并妥善保存。 （3）监察员定期对研究数据进行稽查，确认所有调查表填写完整、正确。如有错误和遗漏，及时要求调查员改正，保存修改内容，并由调研员签名并注明日期。 （4）电子数据文件包括数据库、检查程序、分析程序、分析结果、编码本和说明文件等，应分类保存，并有多个备份保存于不同磁盘或记录介质上，妥善保存，防止损坏。 （5）研究期间出现的不良事件，应将其症状、程度、出现时间、持续时间、处理措施、经过等记录于病理报告表，评价其与研究药物的相关性，并有研究者详细记录，签名并注明日期。同时必须在第一时间（2小时内）向课题负责人和主研单位基地办报告，主研单位基地办应在24小时内报告药品监督管理局和伦理委员会。研究者要在报告上签名并注明日期。保存数据备查。 （6）试验完成后，临床试验中的所有资料，包括研究方案、患者签名的知情同意书、患者的医院原始记录、填写完整的CRF表等，经研究员和监察员审核、签字后，根据中国GCP的要求进行保存和管理至临床试验工作终止后2年。除国家或地方监管部门，或伦理委员会按照要求查阅外，不得以任何形式提供给他人。2.数据统计分析（1）统计软件：数据统计分析应用SPSS21.0统计软件。（2）基本原则：所有统计推断均采用双侧检验，具有统计意义的检验水准定为0.05，参数的可信区间估计采用95％可信区间。尽可能采用参数方法，当数据不满足参数方法条件时，可采用数据转换方法使其满足条件，若仍不满足，可考虑采用非参数方法。（3）描述统计量：计量资料给出均数、标准差进行描述；不满足正态性用中位数和四分位数间距进行统计学描述；计数资料给出频数分布及相应的百分数。（4）基线特征指标的均衡性分析：对患者的人口学信息、病程、萎缩程度及病理特征基线特征情况等进行统计描述。计量资料符合正态方差齐采用方差分析或两独立样本T检验，否则使用秩和检验；计数资料采用卡方检验或Fisher确切检验。（5）缺失数据处理：对于缺失值采用均值插补或同类均值插补。（6）疗效分析：疗效指标同组患者治疗前后比较：定量变量用配对ｔ检验；定性比例采用McNemar X2检验。组间比较：计量资料符合正态方差齐采用方差分析或两独立样本T检验，否则使用秩和检验；计数资料采用卡方检验进行分析。等级变量采用秩和检验。在实验设计时对可能预见到的混杂偏倚进行控制，数据处理中对可能影响疗效结局变量的混杂因素进行分层分析、Logistic回归分析进行控制。

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

In order to improve the quality of research and reduce research bias, real-time input of subject data, third-party data management, and third-party blind statistical analysis will be carried out during the research process. The third-party will conduct data analysis and issue statistical analysis reports. 1. Data Management The requirements are as follows: (1) The researcher observes the original data according to the actual conditions of the subjects and records the CRF table. Researchers need to ensure that the data is true, complete and accurate. All items must be filled in, no blanks or omissions are allowed. When making any corrections, only lines can be drawn. The revised content shall be marked and dated by the investigator. The original records shall not be erased or overwritten. (2) Data entry and management are handled by dedicated personnel. Write the corresponding computer program, and use the independent double entry method for data entry. The data administrator checks the data, and promptly asks the investigator for any questions found, and the data administrator confirms and revises the data based on the investigator's answers. The content of the error and the result of the modification shall be truthfully recorded and properly kept. (3) The inspector regularly checks the research data and confirms that all the questionnaires are completed and correct. If there are errors or omissions, the investigator shall be asked to correct it in time, save the modified content, and the investigator shall sign and indicate the date. (4) Electronic data files include databases, inspection procedures, analysis procedures, analysis results, codebooks and explanatory documents, etc., which should be stored in categories, and multiple backups should be stored on different disks or recording media, properly stored to prevent damage. (5) For adverse events that occurred during the study period, their symptoms, severity, time of occurrence, duration, treatment measures, and progress should be recorded on the pathology report form, and their relevance to the study drug should be evaluated, and the investigator should record it in detail. Sign and date. At the same time, it must report to the subject in charge and the base office of the main research unit as soon as possible (within 2 hours), and the base office of the main research unit should report to the Drug Administration and the ethics committee within 24 hours. The researcher should sign and date the report. Save the data for future reference. (6) After the trial is completed, all materials in the clinical trial, including the research protocol, the patient’s signed informed consent form, the patient’s original hospital record, and the completed CRF form, etc., will be reviewed and signed by the researcher and supervisor, according to China The requirements of GCP shall be preserved and managed until 2 years after the termination of clinical trials. Except for the national or local regulatory authorities, or the ethics committee to consult as required, it shall not be provided to others in any form. 2. Data statistical analysis (1) Statistical software: SPSS21.0 statistical software is used for data statistical analysis.(2) Basic principles: All statistical inferences use two-sided tests, the statistically significant test level is set at 0.05, and the confidence interval of the parameters is estimated to be 95% confidence interval. Use the parametric method as much as possible. When the data does not meet the parametric method conditions, the data conversion method can be used to make it meet the conditions. If it still does not meet the conditions, the non-parametric method can be considered.(3) Descriptive statistics: the measurement data are given the mean and standard deviation for description; the median and interquartile range are used for statistical description for non-normality; the count data is given the frequency distribution and the corresponding percentage. (4) Balance analysis of baseline characteristic indicators: statistically describe the patient's demographic information, course of disease, degree of atrophy, and baseline characteristics of pathological characteristics. Measurement data conforming to normal variances were analyzed by analysis of variance or two independent samples T test, otherwise, rank sum test was used; count data were used chi-square test or Fisher's exact test. (5) Missing data processing: Mean imputation or mean imputation of the same kind is used for missing values. (6) Efficacy analysis: Comparison of efficacy indicators before and after treatment in the same group of patients: quantitative variables were tested by paired t-test; qualitative ratios were tested by McNemar X2. Comparison between groups: measurement data conforming to normal variances were analyzed by analysis of variance or two independent samples T test, otherwise, rank sum test was used; count data was analyzed by chi-square test. Rank-sum test is used for rank variables. In the experimental design, the confounding bias that may be foreseen was controlled. In the data processing, the confounding factors that may affect the outcome of the efficacy were controlled by stratified analysis and Logistic regression analysis.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2023-08-23 15:14:50