ChiCTR2400089178 版本V1.0 版本创建时间2024/09/03 14:08:50 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：

ChiCTR2400089178 

最近更新日期：

Date of Last Refreshed on：

2024-09-03 14:08:44 

注册时间：

Date of Registration：

2024-09-03 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

人胎盘脂多糖注射液用于慢性阻塞性肺疾病急性加重患者的临床观察研究

Public title：

Clinical observation of human placental lipopolysaccharide injection used in patients with acute exacerbation of chronic obstructive pulmonary disease

注册题目简写：

English Acronym：

研究课题的正式科学名称：

人胎盘脂多糖注射液用于慢性阻塞性肺疾病急性加重患者的临床观察研究

Scientific title：

Clinical observation of human placental lipopolysaccharide injection used in patients with acute exacerbation of chronic obstructive pulmonary disease

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：

吴尚洁 

研究负责人：

吴尚洁 

Applicant：

wu shangjie 

Study leader：

wu shangjie 

申请注册联系人电话：

Applicant telephone：

+86 136 0748 8688

研究负责人电话：

Study leader's telephone：

+86 136 0748 8688

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：

wushangjie@csu.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

wushangjie@csu.edu.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：

湖南省长沙市人民中路139号

研究负责人通讯地址：

湖南省长沙市人民中路139号

Applicant address：

139 Renmin Middle Road, Changsha City, Hunan Province

Study leader's address：

139 Renmin Middle Road, Changsha City, Hunan Province

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：

中南大学湘雅二医院

Applicant's institution：

The Second Xiangya Hospital, Central South University

研究负责人所在单位：

中南大学湘雅二医院

Affiliation of the Leader：

The Second Xiangya Hospital, Central South University

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：

LYEC2024-0267

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：

中南大学湘雅二医院临床研究伦理委员会

Name of the ethic committee：

Clinical Research Ethics Committee, Second Xiangya Hospital, Central South University

伦理委员会批准日期：

Date of approved by ethic committee：

2024-07-03 00:00:00

伦理委员会联系人：

陈晋东

Contact Name of the ethic committee：

chen jindong

伦理委员会联系地址：

湖南省长沙市人民中路139号

Contact Address of the ethic committee：

139 Renmin Middle Road, Changsha City, Hunan Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 731 8529 2476

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：

中南大学湘雅二医院

Primary sponsor：

The Second Xiangya Hospital, Central South University

研究实施负责（组长）单位地址：

湖南省长沙市人民中路139号

Primary sponsor's address：

139 Renmin Middle Road, Changsha City, Hunan Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

湖南省

市(区县)：

Country：

China

Province：

Hunan

City：

单位(医院)：

中南大学湘雅二医院

具体地址：

湖南省长沙市人民中路139号

Institution
hospital：

The Second Xiangya Hospital, Central South University

Address：

139 Renmin Middle Road, Changsha City, Hunan Province

经费或物资来源：

湖南一格制药有限公司

Source(s) of funding：

Hunan Yige pharmaceutical Co., LTD

Target disease：

Acute exacerbation of chronic obstructive pulmonary disease

Target disease code：

研究类型：

干预性研究

Study type：

Interventional 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：

通过小样本临床观察研究，评价人胎盘脂多糖注射液用于慢性阻塞性肺疾病急性加重患者的临床疗效与作用特点，指导临床合理用药 。  

Objectives of Study：

Through small sample clinical observation and study, to evaluate the clinical efficacy and functional characteristics of human placental lipopolysaccharide injection in patients with acute exacerbation of chronic obstructive pulmonary disease, and guide clinical rational drug use.

药物成份或治疗方案详述：

试验组：人胎盘脂多糖注射液+基础治疗 对照组：人胎盘脂多糖注射液安慰剂+基础治疗 人胎盘脂多糖注射液/人胎盘脂多糖注射液安慰剂说明书用法用量： 用法用量：肌内注射。一次2ml，一日或隔日一次，20次为一疗程， 观察周期：人胎盘脂多糖治疗1个疗程，随访观察1年。 ? 

Description for medicine or protocol of treatment in detail：

Experimental group: Human placental lipopolysaccharide injection+basic treatment Control group: placebo with human placental lipopolysaccharide injection and basic treatment Human Placental Lipopolysaccharide Injection/Human Placental Lipopolysaccharide Injection Placebo Instructions Usage and Dosage: Usage and dosage: Intramuscular injection. 2ml once, once a day or every other day, 20 times for one course of treatment, Observation period: One course of treatment with human placental lipopolysaccharide, followed up for one year.  

纳入标准：

1. 受试者在签署知情同意书时年龄≥40岁，性别不限； 2. 入选前至少一年的COPD诊断记录； 3. 符合最新GOLD 2024指南COPD急性加重定义（附件一）； 4. 受试者知情，自愿签署知情同意书，并同意按照试验方案的要求参加所有的访视及检查、治疗。

Inclusion criteria

1. Participants must be at least 40 years old and of any gender at the time of signing the informed consent form; 2. COPD diagnosis records for at least one year prior to enrollment; 3. Complies with the latest GOLD 2024 guidelines for the definition of acute exacerbation of COPD (Attachment 1); 4. The subjects are informed, voluntarily sign the informed consent form, and agree to participate in all visits, examinations, and treatments according to the requirements of the trial protocol.

排除标准：

1. 现患以下任一疾病：活动性肺结核、肺癌、肺水肿、囊性纤维化、闭塞性细支气管炎、结节病（肉样瘤病）等，或经研究医生判定参加本试验对患者有安全性风险和/或影响研究结果分析的具有临床意义的肺纤维化、肺动脉高压、间质性肺疾病、活动性支气管扩张。 2. 任何不稳定的疾病，包括但不限于：心血管、胃肠道、肝、肾、神经系统、肌肉骨骼、传染性、内分泌、代谢、血液学、精神疾病、重大肢体功能障碍或认知受损，并且研究者认为： a. 在整项研究期间影响受试者的安全性。 b. 影响研究结果及其解释。 c. 妨碍受试者并造成无法完成整个研究过程和/或遵守研究访视时间计划表和研究步骤。 3. 随机分组前仍存在除COPD相关感染以外的其他需要全身抗感染治疗的疾病。 4. 不稳定的心血管疾病（包括但不限于：缺血性心脏病、心律不齐、心肌病、不稳定的中度至重度心力衰竭（NYHA III-IV级和/或LVEF<30%）、临床上显著的主动脉狭窄、未受控制的动脉高压或任何其他相关的心血管疾病），且根据研究者的判断，可能会使受试者面临风险或对研究结果产生影响。 5. 诊断为肺源性心脏病、肺动脉源性肺动脉高压和/或右心室衰竭。 6. 筛选期有活动性肝病证据，包括有黄疸、ALT或AST>2ULN，或TBIL>2ULN（除非由Gilbert病所致）。注：如果研究者认为受试者无活动性肝病并且符合其他入选标准，则一过性升高的ALT/AST/TBIL在随机前消退也可接受。 7. 入选前一年内有活动性重度炎症性肠病或结肠炎病史，或随机化前4周内发生过不明原因的腹泻。 8. 已知有免疫缺陷病史，包括HIV-1或HIV-2检测阳性。 9. 有乙型肝炎或丙型肝炎阳性病史或治疗，治愈的丙型肝炎除外。 a. HBsAg检测阳性。 b. 抗HBc检测阳性：抗HBc抗体检测呈阳性但HBsAg呈阴性的受试者如果HBV DNA检测结果为阴性，则可以入组。 c. 抗丙型肝炎抗体检测呈阳性：抗丙型肝炎抗体检测呈阳性的受试者，如果他们的丙型肝炎病毒RNA检测结果为阴性且无肝硬化，则可以入组。 10. 目前或过去5年内患有恶性肿瘤，经适当无创治疗的基底细胞癌和皮肤鳞状细胞癌以及入选前治疗成功1年以上的宫颈原位癌除外。疑似恶性肿瘤或未确定的肿瘤。 11. 研究者或有资质的指定人员认为受试者有活动性肺结核（TB）的证据。最近（2年内）纯化蛋白衍生物（PPD）检测或QuantiFERON-TB检测首次或新发现阳性的受试者需要在入选前完成适当的治疗疗程。将根据当地SoC进行评估，可能包括根据当地指南确定的病史和体格检查、胸部X线检查和/或TB检查。 12. 部分或全肺切除病史（单叶或肺段切除术除外）。入选前6个月内进行过手术或内镜（如瓣膜）肺减容术。研究期间预期需要进行肺减容手术。 13. 随机化前2周内使用过全身性皮质类固醇、大环内酯类抗生素或其他免疫抑制或免疫增强药物治疗。 14. 妊娠、哺乳期妇女及试验期间不能严格避孕的患者。 15. 对试验药物及其成分过敏。 16. 近3个月内参加过其他临床试验。 17. 随机化前30天内接种过减毒活疫苗、接受血液制品或免疫球蛋白治疗。 18. 研究者认为不适宜参加本临床试验。

Exclusion criteria：

1. Currently suffering from any of the following diseases: active pulmonary tuberculosis, lung cancer, pulmonary edema, cystic fibrosis, bronchiolitis obliterans, sarcoidosis (sarcoidosis), etc., or clinically significant pulmonary fibrosis, pulmonary arterial hypertension, interstitial lung disease, active bronchiectasis that have been determined by the research doctor to pose a safety risk and/or affect the analysis of research results for patients participating in this trial. 2. Any unstable disease, including but not limited to: cardiovascular, gastrointestinal, liver, kidney, nervous system, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, major limb dysfunction or cognitive impairment, and the researcher believes that: a. Affects the safety of participants throughout the entire study period. b. Impact research results and their explanations. c. Obstructing the subjects and causing them to be unable to complete the entire study process and/or comply with the study visit schedule and study steps. 3. Before randomization, there were still other diseases that required systemic anti infective treatment, except for COPD related infections. 4. Unstable cardiovascular diseases (including but not limited to: ischemic heart disease, arrhythmia, cardiomyopathy, unstable moderate to severe heart failure (NYHA III-IV grade and/or LVEF<30%), clinically significant aortic stenosis, uncontrolled arterial hypertension, or any other related cardiovascular diseases), which, in the judgment of the researcher, may pose risks to the subjects or affect the research results. 5. Diagnosed as pulmonary heart disease, pulmonary arterial hypertension, and/or right ventricular failure. During the screening period, there is evidence of active liver disease, including jaundice, ALT or AST>2ULN, or TBIL>2ULN (unless caused by Gilbert's disease). Note: If the researcher considers that the subject has no active liver disease and meets other inclusion criteria, transient elevation of ALT/AST/TBIL may also be acceptable for regression before randomization. 7. History of active severe inflammatory bowel disease or colitis within the year prior to enrollment, or unexplained diarrhea within the 4 weeks prior to randomization. 8. Known history of immunodeficiency, including testing positive for HIV-1 or HIV-2. 9. History or treatment of positive hepatitis B or C, except for cured hepatitis C. a. HBsAg test positive. b. Positive anti HBc test: Subjects who test positive for anti HBc antibodies but negative for HBsAg can be enrolled if their HBV DNA test result is negative. c. Positive anti hepatitis C antibody test: Subjects who test positive for anti hepatitis C antibodies can be enrolled if their hepatitis C virus RNA test result is negative and they do not have cirrhosis. 10. Patients with malignant tumors currently or within the past 5 years, excluding basal cell carcinoma and squamous cell carcinoma of the skin that have undergone appropriate non-invasive treatment, as well as cervical carcinoma in situ that has been successfully treated for more than 1 year before enrollment. Suspected malignant tumor or undetermined tumor. 11. Researchers or qualified designated personnel believe that the subjects have evidence of active pulmonary tuberculosis (TB). Subjects who have recently (within 2 years) tested positive for purified protein derivatives (PPD) or QuantiFERON TB for the first time or newly discovered positive subjects are required to complete appropriate treatment courses before enrollment. Assessment will be conducted based on local SoC, which may include medical history and physical examination determined according to local guidelines, chest X-ray examination, and/or TB examination. 12. History of partial or total lung resection (excluding unilateral or segmental lung resection). Surgical or endoscopic (such as valve) lung volume reduction surgery has been performed within the first 6 months of enrollment. During the research period, it is expected that lung volume reduction surgery will be required. 13. Use of systemic corticosteroids, macrolide antibiotics, or other immunosuppressive or immune enhancing drugs within 2 weeks prior to randomization. 14. Pregnant and lactating women, as well as patients who cannot strictly use contraception during the trial period. 15. Allergic to the experimental drug and its components. 16. Participated in other clinical trials within the past 3 months. 17. Within 30 days prior to randomization, individuals have received attenuated live vaccines, blood products, or immunoglobulin therapy. 18.Researchers believe that it is not appropriate to participate in this clinical trial.

研究实施时间：

Study execute time：

从 From 2024-09-02 00:00:00至 To 2026-07-30 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-09-06 00:00:00 至 To 2026-07-30 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

30

Group：

Experimental group

Sample size：

干预措施：

人胎盘脂多糖注射液+基础治疗

干预措施代码：

Intervention：

Human placental lipopolysaccharide injection + basic treatment

Intervention code：

组别：

对照组

样本量：

30

Group：

Control group

Sample size：

干预措施：

人胎盘脂多糖注射液安慰剂+基础治疗

干预措施代码：

Intervention：

Human placental lipopolysaccharide injection placebo + basal therapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖南 

市(区县)：

  

Country：

China 

Province：

Hunan 

City：

 

单位(医院)：

中南大学湘雅二医院 

单位级别：

三甲 

Institution
hospital：

The Second Xiangya Hospital, Central South University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 广东 

市(区县)：

  

Country：

China 

Province：

Guangdong 

City：

 

单位(医院)：

南方医科大学第七附属医院 

单位级别：

三甲 

Institution
hospital：

The Seventh Affiliated Hospital of Southern Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

两组用药后12个月内再次慢性阻塞性肺疾病急性加重的次数

指标类型：

主要指标

Outcome：

The number of recurrent acute exacerbations of chronic obstructive pulmonary disease within 12 months after treatment in both groups

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

访视4肺功能指标（FEV1、FVC）相比基线的变化值

指标类型：

次要指标

Outcome：

Changes in 4 pulmonary function indicators (FEV1, FVC) from baseline were investigated

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

各个访视慢性阻塞性肺疾病评估测试（CAT）总评分、CCQ总评分相比基线的变化

指标类型：

次要指标

Outcome：

Each visit Chronic obstructive pulmonary Disease Assessment Test (CAT) total score, CCQ total score compared to baseline change

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

各个访视治疗期内吸入沙丁胺醇气雾剂使用次数

指标类型：

次要指标

Outcome：

Times of inhaled salbutamol aerosol use during each visit treatment period

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

各个访视治疗后血清IL-2、IL-4、IL-10、IFN-γ、TNF-α、IL-8、IL-1β、IL-6水 平较基线变化

指标类型：

次要指标

Outcome：

Serum levels of IL-2, IL-4, IL-10, IFN-γ, TNF-α, IL-8, IL-1β, and IL-6 changed from baseline after each visit

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

IgA、IgG、IgM、CD3+、CD4+、CD8+、CD45+、总T淋巴细胞、NK细胞水平较基线变化

指标类型：

次要指标

Outcome：

The levels of IgA, IgG, IgM, CD3+, CD4+, CD8+, CD45+, total T lymphocytes and NK cells were changed from baseline

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

治疗1年患者再发COPD急性加重的发生率

指标类型：

次要指标

Outcome：

Incidence of recurrent acute exacerbations of COPD in patients treated for 1 year.

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：

血液

组织：

Sample Name：

Blood

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：

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：

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 40 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）：

本研究采用分层区组随机化方法，分层因素为研究中心。随机表由不参与本研究统计分析工作的统计人员依据SAS软件的PLAN过程按试验组:安慰剂对照组=1:1的比例产生，其中区组长度、初始种子数等参数和随机表作为一级盲底，一式两份，分别保存于研究负责单位和资助方。 制作随机表的统计人员及其他与本研究无关的人员负责研究药品的包装编盲工作，研究药品完成包装后，每个受试者的药品都将贴有唯一的药物编号标签，该药物编号即随机表中的药物编号，试验过程中保持不变。各中心按知情时间先后顺序，从小到大分配药物编号。

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

This study used a stratified block randomization method, with the stratification factor being the research center. The random table was generated by statistical personnel who did not participate in the statistical analysis work of this study according to the PLAN process of SAS software in a ratio of 1:1 between the experimental group and the placebo control group. The parameters such as block length and initial seed number, as well as the random table, were used as the primary blind background. Two copies were kept separately by the research responsible unit and the sponsor. The statistical personnel responsible for creating the random table and other personnel unrelated to this study are responsible for the packaging blinding of the investigational drugs. After the investigational drugs are packaged, each subject's drug will be labeled with a unique drug number tag, which is the drug number in the random table and remains unchanged during the trial process. Each center assigns drug codes in ascending order of informed time.

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：

研究采用盲法操作和盲法评价，即采用双盲、双模拟技术。 双盲即研究者方（对受试者进行筛选的人员、终点评价人员以及对方案依从性进行评价的人员、与临床有关的承担单位人员等）和受试者方（或其家属、监护人或陪护人员等）对处理分组均应处于“盲态”。

Blinding：

The study adopts blind operation and blind evaluation, that is, double-blind and double-simulation technology. Double-blind means that both the investigator (the person who screens the subjects, the end-point evaluator and the person who evaluates the compliance of the scheme, the person who undertakes the clinical work, etc.) and the subject (or their family members, guardians or accompanying personnel, etc.) should be in a "blind state" in the treatment grouping.

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

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）：

无

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

None

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：

本研究采用电子数据采集系统（EDC）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：

In this study, electronic data acquisition system (EDC) is used for data management

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2024-09-03 14:08:44