ChiCTR2000037766 版本V1.2 版本创建时间2020/11/01 13:11:23 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：

 ChiCTR2000037766 

最近更新日期：

Date of Last Refreshed on：

 2020-11-01 13:07:21 

注册时间：

Date of Registration：

 2020-08-31 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

请于伦理委员会批准后才开始征募参试者，并与我们联系上传伦理批件。 大黄煎保留灌肠治疗肝硬化 自发性细菌性腹膜炎的临床研究

Public title：

Clinical study on Rhubarb decoction retention enema in the treatment of liver cirrhosis with spontaneous bacterial peritonitis

注册题目简写：

English Acronym：

研究课题的正式科学名称：

大黄煎保留灌肠治疗肝硬化 自发性细菌性腹膜炎的临床研究

Scientific title：

Clinical study on Rhubarb decoction retention enema in the treatment of liver cirrhosis with spontaneous bacterial peritonitis

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：

沈一芃 

研究负责人：

沈一芃 

Applicant：

Shen Yipeng 

Study leader：

Shen Yipeng 

申请注册联系人电话：

Applicant telephone：

 +86 18061699984

研究负责人电话：

Study leader's
telephone：

+86 18061699984

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：

 1040232511@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 1040232511@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：

上海市静安区芷江中路274号上海市中医医院

研究负责人通讯地址：

上海市静安区274号

Applicant address：

274 Zhijiang Middle Road, Jing'an District, Shanghai, China

Study leader's address：

274 Zhijiang Middle Road, Jing'an District, Shanghai, 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：

上海市中医医院

Applicant's institution：

Shanghai Hospital of traditional Chinese Medicine

研究负责人所在单位：

上海市中医医院

Affiliation of the Leader：

Shanghai Hospital of Traditional Chinese Medicine

是否获伦理委员会批准：

否

Approved by ethic committee：

No

伦理委员会批件文号：

Approved No. of ethic committee：

伦理委员会批件附件：

Approved file of Ethical Committee：

批准本研究的伦理委员会名称：

Name of the ethic committee：

伦理委员会批准日期：

Date of approved by ethic committee：

 2013-08-26 00:00:00

伦理委员会联系人：

Contact Name of the ethic committee：

伦理委员会联系地址：

Contact Address of the ethic committee：

伦理委员会联系人电话：

Contact phone of the ethic committee：

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：

上海市中医医院

Primary sponsor：

Shanghai Hospital of traditional Chinese Medicine

研究实施负责（组长）单位地址：

上海市静安区芷江中路274号上海市中医医院

Primary sponsor's address：

274 Zhijiang Middle Road, Jing'an District, Shanghai, 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)：

上海市

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

上海市中医医院

具体地址：

上海市静安区芷江中路274号

Institution
hospital：

Shanghai Hospital of traditional Chinese Medicine

Address：

274 Zhijiang Middle Road, Jing'an District

经费或物资来源：

专项资金

Source(s) of funding：

Special funds

研究疾病：

自发性细菌性腹膜炎  

Target disease：

spontaneous bacterial peritonitis,SBP

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：

 I期临床试验 

Study phase：

1

研究设计：

横断面 

Study design：

Cross-sectional 

研究目的：

本研究重点探讨大黄煎灌肠对肝硬化自发性细菌性腹膜炎患者的临床疗效及安全性，以期为中药灌肠辅助治疗肝硬化自发性细菌性腹膜炎提供临床依据。  

Objectives of Study：

This study focused on the clinical efficacy and safety of Rhubarb decoction enema in the treatment of liver cirrhosis patients with spontaneous bacterial peritonitis, in order to provide clinical basis for the adjuvant treatment of liver cirrhosis with spontaneous bacterial peritonitis.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.1.1西医诊断标准：
（1）符合 2015 年中华医学会肝病学分会制定的《慢性乙型肝炎防治指南》中肝硬化诊断标准: 临床上常根据有无主要并发症将肝硬化分为代偿期及失代偿期。代偿期肝硬化影像学、生化学或血液学检查有肝细胞合成功能障碍或门静脉高压症(如脾功能亢进及食管胃底静脉曲张)证据，或组织学符合肝硬化诊断, 但无食管胃底静脉曲张破裂出血、腹水或肝性脑病等严重并发症。失代偿期肝硬化可食管胃底静脉曲张破裂出血、肝性脑病、腹水等其他严重并发症。
为了更准地预测肝硬化患者的疾病进展，判断死亡风险，可按五期分类法评估肝硬化并发症情况，1 期：无静脉曲张，无腹水；2 期：有静脉曲张，无出血及腹水；3 期：有腹水，无出血，伴或不伴静脉曲张；4 期：有出血，伴或不伴腹水；5 期：脓毒血症。1、2 期为代偿性肝硬化，3 至 5 期为失代偿性肝硬化。1、2、3、4 和 5 期 1 年病死率分别为<1%，3%-4%，20%、50%和 60%。并发症的出现与肝硬化患者预后与死亡风险密切相关。 Child-Pugh分级：根据肝性脑病、腹水、血清总胆红素、血清白
蛋白、凝血酶原时间指标来评估肝功能情况，反应病情严重程度。
（2）符合《2010 年 EASL 肝硬化自发性细菌性腹膜炎临床实践指南》中镜检发现腹水中性粒细胞数量>0.25×109/L。
1.1.2中医证型诊断标准：
参考 2002 年中国医药科技出版社《中药新药临床研究指导原则（试行）》中湿热蕴脾证和血瘀证。
湿热蕴脾证：
主证：脘腹胀闷，口渴少饮，食少纳呆，大便溏而不爽，舌质红，舌苔黄腻；
次症：肢体困重，身热不扬或汗出不解，腹胀满，恶心欲呕，身目发黄色鲜明，脉濡数。
血瘀证：
主证：刺痛、痛有定处、拒按，脉络淤血（诸如口唇、齿龈、爪甲紫暗，肤表赤缕，或腹壁青筋外露），皮下瘀斑，癥积，离经之血，舌质紫暗或有瘀斑、瘀点，舌脉粗张，脉涩、无脉或沉弦、弦迟；
次症：肌肤甲错，肢体麻木或偏瘫，痴癫，狂躁、善忘，局部感觉异常，外伤史、手术史及人工流产史。
湿热蕴脾证需符合主证 3 项（舌象必备）；或主证 2 项（舌象必备），即可诊断。血瘀证主证 2 项，或主证 1 项、次症 2 项，即可诊断。本研究的湿热瘀结证需符合血瘀的诊断条件，同时具备湿热蕴脾证的诊断条件。
纳入研究的患者需共同满足西医诊断要求及中医证型诊断要求。

Inclusion criteria

1.1.1 diagnostic criteria of Western medicine: (1) According to the guidelines for the prevention and treatment of chronic hepatitis B (CHB) formulated by the hepatology branch of Chinese Medical Association in 2015, liver cirrhosis is usually divided into compensatory and decompensated stages according to the main complications. The imaging, biochemical or hematological examination of compensated cirrhosis showed evidence of dysfunction of hepatocyte synthesis or portal hypertension (such as hypersplenism and esophageal and gastric varices), or histology was consistent with the diagnosis of liver cirrhosis, but there were no severe complications such as rupture and bleeding of esophageal and gastric varices, ascites or hepatic encephalopathy. Decompensated cirrhosis can cause esophageal varices bleeding, hepatic encephalopathy, ascites and other serious complications. In order to more accurately predict the disease progression and determine the risk of death in patients with liver cirrhosis, the complications of liver cirrhosis can be evaluated according to the five stage classification: Stage 1: no varicose veins and no ascites; stage 2: varicose veins, no bleeding and ascites; stage 3: ascites, no bleeding, with or without varicose veins; stage 4: bleeding with or without ascites; stage 5: sepsis. 1. Stage 2 was compensatory cirrhosis, and stage 3 to 5 was decompensated cirrhosis. 1. The 1-year mortality of stage 2, 3, 4 and 5 was < 1%, 3% - 4%, 20%, 50% and 60%, respectively. The occurrence of complications is closely related to the prognosis and death risk of patients with liver cirrhosis. Child Pugh classification: according to hepatic encephalopathy, ascites, serum total bilirubin, serum white Protein and prothrombin time were used to evaluate the liver function and reflect the severity of the disease. (2) According to the 2010 EASL guidelines for clinical practice of spontaneous bacterial peritonitis in liver cirrhosis, the number of neutrophils in ascites was more than 0.25 × 109 / L. 1.1.2 diagnostic criteria of TCM syndrome types: Refer to the syndrome of dampness heat accumulating spleen and blood stasis in the guiding principles of clinical research of new Chinese medicine (Trial) published by China Pharmaceutical Science and Technology Press in 2002. Syndrome of dampness heat accumulating spleen Main symptoms: abdominal distension, thirst less drink, less food, loose stool and uncomfortable, red tongue, yellow greasy tongue coating; Secondary symptoms: the limbs are sleepy and heavy, the body is not hot or sweating is not clear, abdominal distension is full, nausea and vomiting, body eyes are yellow and bright, and the pulse is infiltrated. Blood stasis syndrome: Main symptoms: tingling, pain has a fixed place, refused to press, vein congestion (such as lips, gingiva, claw nail dark, skin surface red, or abdominal wall blue veins exposed), subcutaneous ecchymosis, symptom accumulation, blood from menstruation, tongue purple dark or with ecchymosis, petechia, tongue pulse is rough, pulse is astringent, no pulse or sink string, string late; Secondary symptoms: skin nail fault, limb numbness or hemiplegia, madness, forgetfulness, local sensory abnormalities, history of trauma, surgery and artificial abortion. The syndrome of dampness heat accumulating spleen should be diagnosed according to 3 items of main syndrome (necessary for tongue image), or 2 items for main syndrome (necessary for tongue image). Blood stasis syndrome can be diagnosed by 2 main syndromes, 1 main syndrome and 2 secondary symptoms. The syndrome of dampness heat and blood stasis in this study should meet the diagnostic conditions of blood stasis, and have the diagnostic conditions of dampness heat accumulation of spleen. The patients included in the study should meet the diagnostic requirements of Western medicine and TCM syndrome types.

排除标准：

（1）合并消化道出血、肝性脑病、肝肾综合征或肝癌等并发症；
（2）急慢性胰腺炎、多器官功能衰竭、腹部外伤、消化道溃疡穿孔及炎症性肠病等影响肠道功能；
（3）肝病以外的心源性、肾源性、营养障碍性、恶性肿瘤腹膜转移、卵巢肿瘤、结缔组织疾病等引起的腹水；癌性腹膜炎、结核性腹膜炎、继发性腹膜炎（外科急腹症、腹部外伤、手术等）；
（4）合并其他慢性疾病，如心、脑、肾等重要脏器和内分泌、血液系统疾病；
（5）治疗前８周内使用过抗生素、微生态制剂、免疫调节剂及中药类药物；
（6）年龄小于 18 岁或大于 80 岁，孕妇及哺乳期妇；
（7）有灌肠禁忌症；
（8）有精神、心理或神经方面疾病；
（9）合并有其它严重传染病，如肺结核、艾滋病等；
（10）对多种药物过敏的过敏体质；
（11）不愿参加试验和签订知情同意书。

Exclusion criteria：

(1) Complications such as gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome or liver cancer were found; (2) Acute and chronic pancreatitis, multiple organ failure, abdominal trauma, peptic ulcer perforation and inflammatory bowel disease affect intestinal function; (3) Ascites caused by cardiogenic, nephrogenic, dystrophic, malignant tumor peritoneal metastasis, ovarian tumor, connective tissue disease, etc. other than liver diseases; cancerous peritonitis, tuberculous peritonitis, secondary peritonitis (surgical acute abdomen, abdominal trauma, surgery, etc.); (4) Combined with other chronic diseases, such as heart, brain, kidney and other important organs and endocrine and blood system diseases; (5) Antibiotics, probiotics, immunomodulators and traditional Chinese medicine were used in 8 weeks before treatment; (6) Pregnant women and lactating women with age less than 18 years old or over 80 years old; (7) There are contraindications to enema; (8) Mental, psychological or neurological disorders; (9) Combined with other serious infectious diseases, such as tuberculosis, AIDS, etc; (10) Hypersensitivity to a variety of drugs; (11) They were not willing to participate in the experiment and sign informed consent.

研究实施时间：

Study execute time：

从 From 2020-09-01 00:00:00至 To 2022-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2020-09-01 00:00:00 至 To 2022-06-01 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 155

Group：

Experimental group

Sample size：

干预措施：

大黄煎灌肠

干预措施代码：

Intervention：

Rhubarb decoction enema

Intervention code：

组别：

对照组

样本量：

 155

Group：

Control group

Sample size：

干预措施：

常规治疗

干预措施代码：

Intervention：

Conventional treatment

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 上海 

市(区县)：

  

Country：

China

Province：

Shanghai

City：

单位(医院)：

 上海市中医医院 

单位级别：

 三甲 

Institution
hospital：

Shanghai Hospital of Traditional Chinese Medicine

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

血常规

指标类型：

主要指标

Outcome：

routine blood test

Type：

Primary 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：

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 岁 years
最大 Max age 岁 years

性别：

男性

Gender：

Male

随机方法（请说明由何人用什么方法产生随机序列）：

采用随机分组的方法，选取符合纳入标准的肝硬化自发性细菌性腹膜炎患者。对照组为抗生素等常规内科治疗，治疗组在对照组的基础上给予大黄煎灌肠。观察两组治疗前及治疗后第一周、第二周肝功能（ALT、AST、TBIL、ALB）、凝血功能指标（PT、PTA）、炎症指标（WBC、CRP、PCT）、肠道功能（大便次数）。观察并记录治疗过程中 24 小时尿量、腹膜炎症状体征缓解情况、腹水细菌培养及腹水常规生化结果；治疗前后记录患者体重及腹围改变情况，观察及询问患者有无不良反应及并发症的发生并记录。通过临床数据，对比两组短期内在疗效及并发症等方面的优缺点。

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

The patients with spontaneous bacterial peritonitis in cirrhosis were selected by random grouping method. The control group was given routine medical treatment such as antibiotics, while the treatment group was given Rhubarb decoction enema on the basis of the control group. The liver function (alt, AST, TBIL,

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：

Blinding：

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

是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）：

2022年12月30日

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

December 30, 2022

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：

无

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

no

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2020-08-31 23:13:17