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Convalescent plasma for the treatment of severe and critical novel coronavirus pneumonia (COVID-19): a prospective randomized controlled trial
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注册号:

Registration number:

ChiCTR2000029757 

最近更新日期:

Date of Last Refreshed on:

2020-03-09 

注册时间:

Date of Registration:

2020-02-12 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

采集恢复期血浆治疗重型及危重型COVID-19患者的临床试验 

Public title:

Convalescent plasma for the treatment of severe and critical novel coronavirus pneumonia (COVID-19): a prospective randomized controlled trial 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

采集恢复期血浆治疗重型及危重型COVID-19患者的随机、对照临床试验 

Scientific title:

Convalescent plasma for the treatment of severe and critical novel coronavirus pneumonia (COVID-19): a prospective randomized controlled trial 

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:

刘忠 

研究负责人:

曹彬 

Applicant:

Liu Zhong 

Study leader:

Cao Bin 

申请注册联系人电话:

Applicant telephone:

+86 028-61648562 

研究负责人电话:

Study leader's telephone:

13911318339 

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:

Liuz@ibt.pumc.edu.cn 

研究负责人电子邮件:

Study leader's E-mail:

caobin_ben@163.com 

申请单位网址(自愿提供):

Applicant website(voluntary supply):

http://www.ibtcams.ac.cn/ 

研究负责人网址(自愿提供):

Study leader's website(voluntary supply):

https://www.zryhyy.com.cn/ 

申请注册联系人通讯地址:

四川省成都市成华区华彩路26号 

研究负责人通讯地址:

北京市朝阳区樱花园东街 

Applicant address:

26 Huacai Road, Chenghua District, Chengdu, Sichuan 

Study leader's address:

Cherry Blossom Garden East Street, Chaoyang District, Beijing  

申请注册联系人邮政编码:

Applicant postcode:

610000 

研究负责人邮政编码:

Study leader's postcode:

100029 

申请人所在单位:

中国医学科学院输血研究所 

Applicant's institution:

Institute of Blood Transfusion, Chinese Academy of Medical Sciences 

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:

202002 

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:

中国医学科学院输血研究所伦理审查委员会 

Name of the ethic committee:

The Ethics Review Committee of Institute of Blood Transfusion, Chinese Academy of Medical Sciences 

伦理委员会批准日期:

Date of approved by ethic committee:

2020-02-29 

伦理委员会联系人:

魏琼书 

Contact Name of the ethic committee:

Wei Qiongshu 

伦理委员会联系地址:

四川省成都市成华区华彩路26号 

Contact Address of the ethic committee:

26 Huacai Road, Chenghua District, Chengdu, Sichuan 

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:

中日友好医院 

Primary sponsor:

China-Japan friendship hospital 

研究实施负责(组长)单位地址:

北京市朝阳区樱花园东街 

Primary sponsor's address:

Cherry Blossom Garden East Street, Chaoyang 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):

四川

市(区县):

成都

Country:

China

Province:

Sichuan

City:

Chengdu

单位(医院):

中国医学科学院输血研究所

具体地址:

成华区华彩路26号

Institution
hospital:

Institute of Blood Transfusion, Chinese Academy of Medical Sciences

Address:

26 Huacai Road, Chenghua District

国家:

中国

省(直辖市):

湖北

市(区县):

武汉

Country:

China

Province:

Hubei

City:

Wuhan

单位(医院):

华中科技大学同济医学院附属协和医院

具体地址:

解放大道1277号

Institution
hospital:

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Address:

1277 Jiefang Avenue

国家:

中国

省(直辖市):

北京

市(区县):

北京

Country:

China

Province:

Beijing

City:

Beijing

单位(医院):

中日友好医院

具体地址:

北京市朝阳区樱花园东街

Institution
hospital:

China-Japan Friendship Hospital

Address:

Cherry Blossom Garden East Street, Chaoyang District, Beijing

经费或物资来源:

政府 

Source(s) of funding:

Government 

研究疾病:

新型冠状病毒肺炎 

Target disease:

novel coronavirus pneumonia (COVID-19) 

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:

研究目的:

为积极防控新型冠状病毒感染的肺炎,采集新型冠状病毒感染者恢复期的血浆,探索利用恢复期血浆治疗新型冠状病毒感染患者的临床治疗方案。 

Objectives of Study:

In order to actively prevent and control COVID-19, the convalescent plasma of patients with COVID-19 is collected, and the clinical treatment plan of using convalescent plasma to treat patients with COVID-19 is explored. 

药物成份或治疗方案详述:

本研究采用多中心、随机、开放性、平行对照试验设计。计划招募200名重型及危重型COVID-19患者,按照研究中心和疾病分型(重型或危重型)分层随机,以1:1的比例随机分配至试验组或对照组。试验组为常规治疗联合恢复期血浆治疗组,对照组为常规治疗组。完成筛选且符合合格性标准受试者开始研究治疗,所有患者接受常规治疗,包括对症治疗、抗病毒治疗及抗菌治疗等,任何时间发现病情进展均可停止治疗或进行联合其他干预治疗,治疗组在研究第1天接受恢复期血浆治疗,评价疗效和安全性指标。出院或死亡的患者为到达临床终点。所有的受试者将随访至参与研究的第28天或到达临床终点。完成28天观察或到达临床终点的患者视为完成研究。 

Description for medicine or protocol of treatment in detail:

This study is a multicenter, randomized, open, parallel controlled trial. It is planned to recruit 200 patients with severe and critical COVID-19, stratified according to the research center and disease classification (heavy or critical), and randomly allocated to the experimental group or control group at a ratio of 1: 1.The experimental group was a conventional treatment combined with a recovery plasma treatment group, and the control group was a conventional treatment group. Subjects who have completed the screening and meet the eligibility criteria begin study treatment. All patients receive conventional treatment, including symptomatic treatment, antiviral treatment, and antibacterial treatment. At any time, if the disease progresses, treatment can be stopped or combined with other interventions. Treatment group On the first day of the study, patients received convalescent plasma therapy to evaluate efficacy and safety indicators. Patients who were discharged or died were reaching the clinical endpoint. All subjects will be followed up to day 28 of the study or reach the clinical endpoint. Patients who completed 28 days of observation or reached the clinical endpoint were considered to have completed the study.  

研究设计:

随机平行对照 

Study design:

Parallel 

纳入标准:

1.患者签署参与恢复期血浆治疗研究的知情同意书; 2.患者年龄18岁及以上; 3.经过PCR确诊的COVID-19患者; 4.输血前72小时内核酸阳性; 5.影像学证实的肺炎; 6.临床症状达到重型或危重型标准[4] ?重型即符合以下任何一条: a)呼吸窘迫,RR≥30次/分; b)静息状态下,指氧饱和度≤93%; c)动脉血氧分压(PaO2)/吸氧浓度(FiO2)≤300 mmHg(1 mmHg = 0.133 kPa)。 ?危重型即符合以下任何一条: a)出现呼吸衰竭,且需要机械通气; b)出现休克; c)合并其他器官功能衰竭需ICU监护治疗。 7.接受随机分组至任何一组; 8.患者在出现临床研究终点之前一直接受住院治疗; 9.有意愿参加所有必要的研究方向并能参加后续的随访; 10.参加本研究期间不再参与其他抗病毒药物等临床试验研究。 

Inclusion criteria

1. The patient signed an informed consent form to participate in the study of convalescent plasma therapy; 2.The age of the patient is 18 or more than18 years old; 3. COVID-19 patients diagnosed by PCR; 4. Nucleic acid positive within 72 hours before blood transfusion; 5. Pneumonia confirmed by imaging; 6. The clinical symptoms reach the standard of severe or critical. Severe patients meet any of the following: a) respiratory distress, RR ≥ 30 beats / min; b) in resting state, oxygen saturation ≤ 93%; c) partial pressure of oxygen in arterial blood (PaO2) / oxygen concentration (FiO2) ≤ 300mmHg (1mmHg=0.133kPa) Critically ill patients meet any of the following: a) respiratory failure and need mechanical ventilation; b) shock; c) patients with other organ failure need ICU monitoring treatment. 7. Accept random grouping into any group; 8. The patient was hospitalized before the end of the clinical study. 9. Willing to participate in all necessary research directions and be able to participate in follow-up; 10. During the period of participating in this study, they will no longer participate in clinical trials such as other antiviral drugs. 

排除标准:

1.经治医生认为患者不适宜参加本试验,包括可能不配合、不遵守规程要求者或者参加本试验可能使患者处于不安全的情况; 2.孕妇、哺乳期; 3.免疫球蛋白过敏; 4.免疫球蛋白A缺乏症; 5.存在可能使血栓风险增加的疾病,例如冷球蛋白血症、重症难治性高甘油三酯血症、临床明确的单克隆丙种球蛋白血症等; 6.可以检测到高滴度抗新型冠状病毒抗体RBD IgG(高于1:640); 7.在筛查前30天内接受了任何治疗新型冠状病毒感染的试验性治疗; 8.经研究者判断患者存在以下威胁生命的情况,包括但不限于:P/F<100 mmHg,濒死状态或预期生存时间不足24小时,严重感染性休克或弥散性血管内凝血(DIC)等; 9.严重性充血性心力衰竭,或其他经研究者判断存在输注血浆的相对禁忌症。 

Exclusion criteria:

1.The doctor believes that the patient is not suitable to participate in this trial, including those who may not cooperate, do not comply with the requirements of the procedure, or participate in this trial may put the patient in an unsafe situation. 2.Pregnant or lactation periods women; 3.Immunoglobulin allergy; 4.Immunoglobulin A deficiency; 5.There are diseases that may increase the risk of thrombosis, such as cold globulinemia, severe refractory hypertriglyceridemia, clinically defined monoclonal gamma globulinemia, etc. 6.High titer of anti-novel coronavirus antibody RBDIgG (higher than 1) could be detected. 7.Received any experimental treatment for novel coronavirus infection within 30 days before screening; 8.The researchers judged that the patients had the following life-threatening conditions, including, but not limited to, Phammer F < 100mmHg, near-death state or expected survival time less than 24 hours, severe septic shock or disseminated intravascular coagulation ((DIC)), etc 9.Severe congestive heart failure, or other relative contraindications for plasma transfusion determined by researchers. 

研究实施时间:

Study execute time:

From2020-02-14To 2021-02-05 

征募观察对象时间:

Recruiting time:

From2020-02-14To 2021-01-05 

干预措施:

Interventions:

组别:

试验组

样本量:

100

Group:

Experimental group

Sample size:

干预措施:

常规治疗联合恢复期血浆治疗

干预措施代码:

Intervention:

Conventional treatment and convalescent plasma therapy

Intervention code:

组别:

对照组

样本量:

100

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):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

Wuhan 

单位(医院):

华中科技大学同济医学院附属协和医院 

单位级别:

三级医院 

Institution
hospital:

Union Hospital, Tongji Medical College, Huazhong university of Science and Technology  

Level of the institution:

Tertiary Hospital 

国家:

中国 

省(直辖市):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

Wuhan 

单位(医院):

湖北省武汉市红十字会医院 

单位级别:

二级医院 

Institution
hospital:

Red Cross Hospital in Wuhan of Hubei Province  

Level of the institution:

Secondary Hospital 

国家:

中国 

省(直辖市):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

Wuhan 

单位(医院):

武汉血液中心 

单位级别:

事业单位 

Institution
hospital:

Wuhan Blood Center  

Level of the institution:

Institution 

国家:

中国 

省(直辖市):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

 

单位(医院):

华中科技大学同济医学院附属同济医院 

单位级别:

三级医院 

Institution
hospital:

Tongji Hospital, Tongji Medical College, Huazhong university of Science and Technology  

Level of the institution:

Tertiary Hospital 

国家:

中国 

省(直辖市):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

 

单位(医院):

武汉亚洲心脏病医院 

单位级别:

三级医院 

Institution
hospital:

Wuhan Asia Heart Hospital  

Level of the institution:

Tertiary Hospital 

国家:

中国 

省(直辖市):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

Wuhan 

单位(医院):

武汉市中心医院 

单位级别:

三级医院 

Institution
hospital:

The Central Hospital of Wuhan  

Level of the institution:

Tertiary Hospital 

国家:

中国 

省(直辖市):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

Wuhan 

单位(医院):

武汉市第一医院 

单位级别:

三级医院 

Institution
hospital:

Wuhan No.1 Hospital  

Level of the institution:

Tertiary Hospital 

国家:

中国 

省(直辖市):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

Wuhan 

单位(医院):

武汉市肺科医院 

单位级别:

三级医院 

Institution
hospital:

Wuhan Lung Hospital  

Level of the institution:

Tertiary Hospital 

国家:

中国 

省(直辖市):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

Wuhan 

单位(医院):

武汉市妇幼保健院 

单位级别:

三级医院 

Institution
hospital:

Wuhan Maternal and Child Health Hospital  

Level of the institution:

Tertiary Hospital 

国家:

中国 

省(直辖市):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

Wuhan 

单位(医院):

中国人民解放军西部战区总医院 

单位级别:

三级医院 

Institution
hospital:

General Hospital of the Western Theater of the People's Liberation Army  

Level of the institution:

Tertiary Hospital 

国家:

中国 

省(直辖市):

湖北 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

Wuhan 

单位(医院):

武汉大学中南医院 

单位级别:

三级医院 

Institution
hospital:

Zhongnan Hospital of Wuhan University  

Level of the institution:

Tertiary Hospital 

国家:

中国 

省(直辖市):

上海 

市(区县):

上海 

Country:

China 

Province:

Shanghai 

City:

Shanghai 

单位(医院):

长海医院 

单位级别:

三级医院 

Institution
hospital:

Changhai Hospital  

Level of the institution:

Tertiary Hospital 

测量指标:

Outcomes:

指标中文名:

28天死亡率

指标类型:

次要指标 

Outcome:

28-day mortality

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

住院时间

指标类型:

次要指标 

Outcome:

Hospitalization time

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

住ICU时间

指标类型:

次要指标 

Outcome:

ICU hospitalization

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

感染期间有创机械通气时间

指标类型:

次要指标 

Outcome:

Invasive mechanical ventilation during infection

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

感染期间ECMO持续时间

指标类型:

次要指标 

Outcome:

ECMO duration during infection

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

病毒核酸转为阴性的比例(输血后3天)

指标类型:

次要指标 

Outcome:

Proportion of viral nucleic acid negative (3 days after transfusion)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

实验室检查、生命体征的记录结果

指标类型:

附加指标 

Outcome:

Results of laboratory tests and vital signs

Type:

Additional indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

严重不良事件(SAE)的累积发生率

指标类型:

附加指标 

Outcome:

Cumulative incidence of severe adverse events (SAE)

Type:

Additional indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

不良事件(AE),3级和4级AE的累积发生率

指标类型:

附加指标 

Outcome:

Cumulative incidence of adverse events (AE), grades 3 and 4 AE

Type:

Additional indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血浆输注不良反应的发生率

指标类型:

副作用指标 

Outcome:

Incidence of adverse plasma transfusion reactions

Type:

Adverse events 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

随机分组后至临床改善的天数

指标类型:

主要指标 

Outcome:

the number of days between randomised grouping and clinical improvement

Type:

Primary indicator 

测量时间点:

入组28天

测量方法:

临床改善定义为患者入院状态的6分等级量表评分降低2分或者出院,6分等级量表包括:6分:死亡; 5分:住院接受ECMO和/或机械通气; 4分:住院接受无创通气和/或高流量氧疗; 3分:住院接受氧疗(但不需要高流量或无创通气); 2分:住院不需要接受氧疗;1分:出院。

Measure time point of outcome:

within 28 days admission

Measure method:

Clinical improvement is defined as the patient's admission status of 6 grade scale score reduced by 2 points or discharged.

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

其它 

说明

Fate of sample:

Others 

Note:

标本中文名:

唾液

组织:

Sample Name:

Saliva

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:

正在进行

Recruiting

年龄范围:

Participant age:

最小 Min age 18 years
最大 Max age - 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):

本研究的随机方法如下:受试者按照1:1的比例,随机分配至试验组(常规治疗联合恢复期血浆治疗组)或者对照组(常规治疗组),并依照该组别的治疗方案接受治疗。本研究采用分层区组随机,分层因素为研究中心和疾病的分型(重型vs危重型),各家中心通过IWRS竞争入组。受试者完成本研究的所有筛选评估项目,符合入排标准入组后,就会被分配一个由IWRS生成的随机号,此随机号将连接受试者进入指定的治疗组(试验组或对照组)接受治疗。随机后的受试者无论出于任何原因退出研究,此受试者的随机号都将保留。IWRS工作人员将只负责随机分组的分配,不参与任何具体试验运营工作。

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

The randomization method of this study is as follows: Subjects are randomly assigned to the experimental group (conventional treatment combined with convalescent plasma treatment group) or the control group (conventional treatment group) according to the ratio of 1: 1, and receive according to the treatment p

盲法:

本研究未设置盲法。

Blinding:

There is no blind method in this study.

试验完成后的统计结果(上传文件):

Calculated Results ater
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):

项目完成且统计数据后公开,以论文或报告的形式公开

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

After the project is completed and the statistics are analysed, it will be published in the form of a thesis or report.

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:

病例记录表

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

Case Record Form, CRF

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:

 2020-02-12
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