Today is 2020-04-01

A randomized, open-label controlled trial for the efficacy and safety of Pirfenidone in patients with severe and critical novel coronavirus pneumonia (COVID-19)
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注册号:

Registration number:

ChiCTR2000030333 

最近更新日期:

Date of Last Refreshed on:

2020-02-29 

注册时间:

Date of Registration:

2020-02-28 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

吡非尼酮治疗武汉新型冠状病毒感染(COVID-19)重型及危重型患者的疗效和安全性随机、开放、 空白对照的研究 

Public title:

A randomized, open-label controlled trial for the efficacy and safety of Pirfenidone in patients with severe and critical novel coronavirus pneumonia (COVID-19) 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

吡非尼酮治疗武汉新型冠状病毒感染(COVID-19)重型及危重型患者的疗效和安全性随机、开放、 空白对照的研究 

Scientific title:

A randomized, open-label study to evaluate the efficacy and safety of Pirfenidone in patients with severe and critical novel coronavirus infection (COVID-19) 

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:

张惠兰 

研究负责人:

张惠兰 

Applicant:

Huilan Zhang 

Study leader:

Huilan Zhang 

申请注册联系人电话:

Applicant telephone:

+86 15391532171 

研究负责人电话:

Study leader's telephone:

+86 15391532171 

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:

huillanz_76@163.com 

研究负责人电子邮件:

Study leader's E-mail:

huillanz_76@163.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:

湖北省武汉市解放大道1095号 

研究负责人通讯地址:

湖北省武汉市解放大道1095号 

Applicant address:

1095 Jiefang Avenue, Wuhan, Hubei, China 

Study leader's address:

1095 Jiefang Avenue, Wuhan, Hubei, 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:

华中科技大学同济医学院附属同济医院 

Applicant's institution:

Tongji Hospital of Tongji Medical College; Huazhong Science and Technology 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:

TJ-C20200108 

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:

华中科技大学同济医学院附属同济医院伦理委员会 

Name of the ethic committee:

The Ethical Committee of Tongji Hospital of Tongji Medical College; Huazhong Science and Technology University 

伦理委员会批准日期:

Date of approved by ethic committee:

2020-01-30 

伦理委员会联系人:

张惠兰 

Contact Name of the ethic committee:

Huilan Zhang 

伦理委员会联系地址:

湖北省武汉市解放大道1095号 

Contact Address of the ethic committee:

1095 Jiefang Avenue, Wuhan, Hubei, China 

伦理委员会联系人电话:

Contact phone of the ethic committee:

+86 027-83663625 

伦理委员会联系人邮箱:

Contact email of the ethic committee:

tj_clinicaltrial@163.com 

研究实施负责(组长)单位:

华中科技大学同济医学院附属同济医院 

Primary sponsor:

Tongji Hospital of Tongji Medical College; Huazhong Science and Technology University 

研究实施负责(组长)单位地址:

湖北省武汉市解放大道1095号 

Primary sponsor's address:

1095 Jiefang Avenue, Wuhan, Hubei, 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):

湖北

市(区县):

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

具体地址:

湖北省武汉市解放大道1095号

Institution
hospital:

Tongji Hospital of Tongji Medical College; Huazhong Science and Technology University

Address:

1095 Jiefang Avenue, Wuhan

经费或物资来源:

华中科技大学同济医学院附属同济医院 

Source(s) of funding:

Tongji Hospital of Tongji Medical College; Huazhong Science and Technology University 

研究疾病:

新型冠状病毒肺炎(COVID-19) 

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:

研究剂量为 400mg、每日 3 次吡非尼酮治疗新型冠状病毒感染的重症肺炎患者 4 周的有效性和安全性。 

Objectives of Study:

The efficacy and safety of pirfenidone at a dose of 400mg 3 times daily for 4 weeks in patients with severe pneumonia with SARS-CoV-2 infection was studied. 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

随机平行对照 

Study design:

Parallel 

纳入标准:

1. 年龄≥ 18 岁; 2. 临床确诊的新型冠状病毒性肺炎患者,包括:符合疑似病例标准的基础上,具备以下病原学 证据之一: (1)呼吸道标本或者血液标本实时荧光 RT-PCR 检测新型冠状病毒核酸阳性; (2) 呼吸道标本或者血液标本病毒基因测序,与已知的新型冠状病毒高度同源。 3. 根据病史症状及胸部CT影像学判断为疑似新性冠状病毒性肺炎病例与随机入组之间的时间 间隔在 4 天以内,症状发作主要以发热作为判定依据,若无发热可使用咳嗽、腹泻或其他相 关症状。影像学改变主要以胸部 CT 为依据。 

Inclusion criteria

1. First diagnosis of novel coronavirus infection 2. Epidemiological history Travel history or residence history of Wuhan City within two weeks before the onset of illness; or patients who have had fever from Wuhan with respiratory symptoms within 14 days before the onset of illness, or have cluster Onset; 3. Clinical manifestations: (1) fever; (2) with the following imaging characteristics of pneumonia; early lesions are limited, showing patchy, subsegmental or segmental ground glass shadows, with or without thickening of lobular septum; progression Increased lesions and expanded scope, involving multiple lung lobes, some lesions consolidation, coexistence of ground glass shadows and consolidation shadows or strip shadows; diffuse lung lesions in severe stages, a few of which show "white lung", mainly consolidation , Combined with ground glass shadow, multiple cord shadow, air bronchus sign. Pleural effusion or lymphadenopathy are rare; (3) The total number of white blood cells is normal or decreased, or the lymphocyte count is decreased in the early stage of onset. On the basis of confirmed cases meeting the criteria for suspected cases, sputum, throat swabs, lower respiratory tract secretions, and other specimens were tested by real-time fluorescent RT-PCR to detect positive nucleic acid of the new coronavirus; or viral gene sequencing was highly similar to known new coronavirus source. Trial diagnosis and treatment plan according to the fourth edition of the new Coronavirus Infected Pneumonia issued by the National Health and Health Commission; Diagnosis criteria for severe pneumonia: One of the following: (1) respiratory distress (>=30 beats / min); (2) In a resting state, SPO2<=93% under inhaled air; (3) PaO2 / FiO2<=300mmHg; Criteria for critical pneumonia: One of the following: (1) Respiratory failure, requiring mechanical ventilation; (2) shock; (3) complicated with other organ failure requires intensive care unit. 

排除标准:

1. 访视 1 时,AST、ALT>1.5 x ULN; 2. 访视 1 时胆红素>1.5x ULN 3. 在访视 1 时,通过 Cockcroft–Gault 公式计算,肌酐清除率<30 mL/min; 4. 合并有潜在慢性肝病患者(Child Pugh A,B 或 C 肝损伤); 5. 既往接受尼达尼布或吡非尼酮治疗; 6. 筛选访视(访视 1)前 1 个月或 6 个半衰期(取较大值)内接受了其他研究性药 物治疗; 7. 基于 ATS/ERS/JRS/ALAT2011 指南(P11-07084)的 IPF 诊断; 8. 以下任何标准定义的明显肺动脉高压(PAH) a. 既往明显的右心衰竭的临床/超声心动图证据; b. 病史包括右心导管显示心脏指数≤2 l/min/m2; c. 需要依前列醇/曲前列环素的胃肠外给药治疗 PAH; 9. 研究者认为的其他具有临床意义的肺部异常; 10.主要的肺外的生理性限制(如胸壁畸形、大量胸腔积液); 11.心血管疾病,任何以下疾病: a. 访视 1 的 6 个月内的严重高血压,治疗后不可控(≥160/100 mmHg); b. 访视 1 的 6 个月内的心肌梗死 c. 访视 1 的 6 个月内的不稳定心绞痛; 12.严重中枢神经系统(CNS)事件史; 13.已知对试验药物过敏; 14.可能干扰检测程序或由研究者判断可能会干扰试验参与或可能使患者在参与本 试验时面临风险的其他疾病; 15.本试验中妊娠、哺乳期或计划妊娠的妇女; 16.患者无法理解或者遵守试验程序,包括在没有帮助的情况下自行完成问卷。  

Exclusion criteria:

1. AST and ALT> 1.5 x ULN at visit 1; 2. bilirubin> 1.5 x ULN at visit 1; 3. At visit 1, calculated by Cockcroft–Gault formula, creatinine clearance <30 mL / min; 4. Patients with potential chronic liver disease (Child Pugh A, B or C liver injury); 5. Previous treatment with nidanib or pirfenidone; 6. One month before the screening visit (Visit 1) or 6 half-lives (whichever is greater) were treated with other research drugs; 7. Diagnosis of IPF based on ATS/ERS/JRS/ALAT2011 guidelines (p11-07084); 8. Significant pulmonary hypertension (PAH) defined by any of the following criteria: (1) Clinical / echocardiographic evidence of previously significant right heart failure; (2) History including right heart catheterization showing a cardiac index <=2 l / min / m2; (3) Prostaglandin required Parenteral administration of Treprostinil for PAH 9. Other clinically significant pulmonary abnormalities that the investigators believe; 10. Major extrapulmonary physiological limitations (eg, chest wall deformity, large pleural effusion); 11. Cardiovascular disease, any of the following diseases: (1) Severe hypertension within 6 months of visit 1, uncontrollable after treatment (>=160 / 100 mmHg) (2) Myocardial infarction within 6 months of visit 1, Unstable angina pectoris within 6 months of Visit 1; 12. History of severe central nervous system (CNS) events; 13. Known allergy to test drug; 14. Other diseases that may interfere with the testing process or that the investigator judges may interfere with the trial participation or may put patients at risk when participating in the trial; 15. Women who were pregnant, lactating or planning to become pregnant in this trial; 16. Patients are unable to understand or follow the trial procedures, including completing the questionnaires themselves without assistance. 

研究实施时间:

Study execute time:

From2020-03-04To 2020-07-07 

干预措施:

Interventions:

组别:

吡非尼酮组

样本量:

147

Group:

Pirfenidone group

Sample size:

干预措施:

标准治疗+吡非尼酮 400mg 一天三次

干预措施代码:

Intervention:

Conventional standard treatment + Pirfenidone 400mg three times a day

Intervention code:

组别:

对照组

样本量:

145

Group:

Control group

Sample size:

干预措施:

标准治疗

干预措施代码:

Intervention:

Conventional standard 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):

 

Country:

China 

Province:

hubei 

City:

 

单位(医院):

荆州市中心医院 

单位级别:

三甲医院 

Institution
hospital:

Jingzhou Central Hospital  

Level of the institution:

Tertiary A Hospital 

测量指标:

Outcomes:

指标中文名:

K-BLD问卷调查

指标类型:

主要指标 

Outcome:

K-bld questionnaire survey

Type:

Primary indicator 

测量时间点:

4周后

测量方法:

Measure time point of outcome:

4 weeks

Measure method:

指标中文名:

指脉氧

指标类型:

主要指标 

Outcome:

Refers to the pulse oxygen

Type:

Primary indicator 

测量时间点:

4周后

测量方法:

Measure time point of outcome:

4 weeks

Measure method:

指标中文名:

胸部CT

指标类型:

主要指标 

Outcome:

chest CT

Type:

Primary indicator 

测量时间点:

4周后

测量方法:

Measure time point of outcome:

4 weeks

Measure method:

指标中文名:

血气

指标类型:

主要指标 

Outcome:

blood gas

Type:

Primary indicator 

测量时间点:

4周后

测量方法:

Measure time point of outcome:

4 weeks

Measure method:

指标中文名:

4 周内距因呼吸系统原因导致死亡的时间

指标类型:

次要指标 

Outcome:

Within 4 weeks of death from respiratory causes

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

4 周内距疾病进展或死亡的时间

指标类型:

次要指标 

Outcome:

Within 4 weeks of disease progression or death

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血常规淋巴细胞的恢复

指标类型:

次要指标 

Outcome:

Routine lymphocyte recovery

Type:

Secondary indicator 

测量时间点:

4周后

测量方法:

Measure time point of outcome:

4 weeks

Measure method:

指标中文名:

血液炎性指标(IL-8 等)的变化

指标类型:

次要指标 

Outcome:

Changes in inflammatory markers of blood (il-8 et al.)

Type:

Secondary indicator 

测量时间点:

4周后

测量方法:

Measure time point of outcome:

4 weeks

Measure method:

指标中文名:

病毒核酸较基线的绝对变化

指标类型:

次要指标 

Outcome:

Absolute change in viral nucleic acid from baseline

Type:

Secondary indicator 

测量时间点:

4周后

测量方法:

Measure time point of outcome:

4 weeks

Measure method:

指标中文名:

肺纤维化生存症状呼吸困难部分评分较基线的绝对变化

指标类型:

次要指标 

Outcome:

Absolute change in pulmonary fibrosis survival symptom dyspnea component score from baseline

Type:

Secondary indicator 

测量时间点:

4周后

测量方法:

Measure time point of outcome:

4 weeks

Measure method:

指标中文名:

肺纤维化生存症状咳嗽部分评分较基线的绝对变化

指标类型:

次要指标 

Outcome:

Absolute change in scores for the cough portion of survival symptoms of pulmonary fibrosis from baseline

Type:

Secondary indicator 

测量时间点:

4周后

测量方法:

Measure time point of outcome:

4 weeks

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:

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):

按照上述纳入诊断的重型及危重型患者,且新型冠状病毒检测阳性的患者292例,患者将被随机化(1:1)进入吡非尼酮组或对照组,然后进入至少 4周治疗期。

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

According to the above included diagnosis of severe and critical patients, and the new coronavirus positive 200 patients, patients will be randomized (1:1) into the pirfenidone group or control group, and then enter a treatment period of at least 4 weeks.

盲法:

未说明

Blinding:

Not stated

试验完成后的统计结果(上传文件):

Calculated Results ater
the Study Completed(upload file):

原始数据公开时间:

The time of sharing IPD:

Within six months after the trial complete

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):

公布在发表论文中

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

Shared in published papers

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:

问卷及量表收集数据,用excel管理数据

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

Collect data from questionnaires and scales, and use excel to manage data

数据管理委员会:

Data Managemen Committee:

有/Yes

注册人:

Name of Registration:

 2020-02-28
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