Today is 2020-12-02

Evaluation the Efficacy and Safety of Hydroxychloroquine Sulfate in Comparison with Phosphate Chloroquine in Mild and Commen Patients with Novel Coronavirus Pneumonia (COVID-19): a Randomized, Open-label, Parallel, Controlled Trial
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注册号:

Registration number:

ChiCTR2000029899 

最近更新日期:

Date of Last Refreshed on:

2020-03-01 

注册时间:

Date of Registration:

2020-02-16 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

硫酸羟氯喹对比磷酸氯喹治疗轻型及普通型新型冠状病毒肺炎(COVID-19)患者的有效性和安全性研究: 一项前瞻性、多中心、开放、随机对照临床研究 

Public title:

Evaluation the Efficacy and Safety of Hydroxychloroquine Sulfate in Comparison with Phosphate Chloroquine in Mild and Commen Patients with Novel Coronavirus Pneumonia (COVID-19): a Randomized, Open-label, Parallel, Controlled Trial  

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

硫酸羟氯喹对比磷酸氯喹治疗轻型及普通型新型冠状病毒肺炎(COVID-19)患者的有效性和安全性研究: 一项前瞻性、多中心、开放、随机对照临床研究 

Scientific title:

Evaluation the Efficacy and Safety of Hydroxychloroquine Sulfate in Comparison with Phosphate Chloroquine in Mild and Commen Patients with Novel Coronavirus Pneumonia (COVID-19): a Randomized, Open-label, Parallel, 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:

沈宁 

研究负责人:

沈宁 

Applicant:

Shen Ning 

Study leader:

Shen Ning 

申请注册联系人电话:

Applicant telephone:

+86 15611908958 

研究负责人电话:

Study leader's telephone:

+86 15611908958 

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:

shenning1972@126.com 

研究负责人电子邮件:

Study leader's E-mail:

shenning1972@126.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:

北京海淀区花园北路49号 

研究负责人通讯地址:

北京海淀区花园北路49号 

Applicant address:

49 Huayuan Road North, Haidian District, Beijing, China 

Study leader's address:

49 Huayuan Road North, Haidian District, Beijing, 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:

北京大学第三医院 

Applicant's institution:

Peking University Third Hospital 

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:

(2020)医伦审第(042-05)号 

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:

北京大学第三医院医学科学研究伦理委员会 

Name of the ethic committee:

Peking University Third Hospital Medical Science Research Ethics Committee 

伦理委员会批准日期:

Date of approved by ethic committee:

2020-02-26 

伦理委员会联系人:

洪雪 

Contact Name of the ethic committee:

Hong Xue 

伦理委员会联系地址:

北京海淀区花园北路49号 

Contact Address of the ethic committee:

49 Huayuan Road North, Haidian District, Beijing, China 

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:

北京大学第三医院 

Primary sponsor:

Peking University Third Hospital 

研究实施负责(组长)单位地址:

北京海淀区花园北路49号 

Primary sponsor's address:

49 Huayuan Road North, Haidian District, Beijing, China 

试验主办单位(项目批准或申办者):

Secondary sponsor:

经费或物资来源:

北京大学第三医院自有经费 

Source(s) of funding:

Peking University Third Hospital self-fund 

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:

上市后药物 

Study phase:

研究目的:

在轻型及普通型新型冠状病毒肺炎患者中探索硫酸羟氯喹对比磷酸氯喹的 疗效和安全性。 

Objectives of Study:

To explore the efficacy and safety of hydroxychloroquine sulfate in comparison with phosphate chloroquine in mild and commen patients with COVID-19 

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. 符合以下标准的确诊病例患者 ① 流行病学史; ② 临床表现(有流行病学史,且符合以下任意2条;无明确流行病学史的,符合临床表现中的全部3条): 发热和/或呼吸道症状; 发病早期白细胞总数正常或降低,或淋巴细胞计数减少; 胸部影像学早期呈现多发小斑片影及间质改变,以肺外带明显。进而发展为双肺多发磨玻璃影、浸润影,严重者可出现肺实变,胸腔积液少见。 ③ 具备以下病原学证据之一者: 呼吸道标本、血液标本或粪便标本实时荧光RT-PCR检测新型冠状病毒核酸阳性; 上述标本病毒基因测序,与已知的新型冠状病毒高度同源。 3. 符合下述轻型及普通型标准的患者 轻型:临床症状轻微,影像学未见肺炎表现; 普通型:具有发热、呼吸道等症状,影像学可见肺炎表现。 4. 三月内未用氯喹、羟氯喹等抗疟药物。 5. 同意从研究药物首次给药后30日内不参加其他临床研究者。 6. 有生育能力的合格受试者(男性和女性)必须同意在试验期间和末次用药后至少3月内与其伴侣一起使用有效节育措施(激素或屏障法或禁欲); 7. 同意参加本研究并愿意自愿签署知情同意书的患者。 

Inclusion criteria

1. Aged >=18 years at time of signing Informed Consent Form; 2. Patients with confirmed cases meeting the following criteria (1) Epidemiology history; (2) Clinical manifestations (epidemiological history and in accordance with any of the following 2 items; no clear epidemiology history, conforms to 3 items in clinical manifestations): Fever and / or respiratory symptoms; In the early stage of the disease, the total leukocyte count was normal or decreased, or the lymphocyte count decreased; Early chest imaging showed multiple small plaques and interstitial changes, which were evident in the extraneous lung. Further, multiple ground-glass shadows and infiltration shadows were found in both lungs, and lung consolidation and pleural effusion were rare in severe cases; (3) Having one of the following etiological evidence: Respiratory tract, blood or fecal samples RT-PCR confirmed infection with 2019-nCoV; The virus genes of the above samples were sequenced and highly homologous to the 2019-nCoV; 3. Patients who meet the following mild and normal criteria; Mild: mild clinical symptoms, no signs of pneumonia on imaging; Normal: fever, respiratory symptoms, imaging manifestations of pneumonia; 4. Antimalarial drugs such as chloroquine and hydroxychloroquine were not used within 3 months; 5. Agree not to participate in other clinical researchers within 30 days from the first administration of the study drug to the last administration; 6. Eligible fertile subjects (male and female) must agree to use effective birth control (hormone or barrier or abstinence) with their partner during the trial period and for at least 3 months after the last dose; 7. Patients who agree to participate in this study and are willing to sign the informed consent form voluntarily. 

排除标准:

1. 明确对4-氨基喹啉类药物和洛匹那韦/利托那韦药物过敏史的患者; 2. 患有严重血液系统疾病的患者; 3. 已知患有视网膜疾病、眼底病变、黄斑病变患者; 4. 已知患有严重肝病,有肝硬化基础疾病或丙氨酸氨基转移酶(ALT)/天门冬氨酸氨基转移酶(AST)升高超过正常上限3倍的患者; 5. 酗酒或正在服用具有肝毒性药物的患者; 6. 已知肾功能受损(估计的肾小球滤过率[eGFR]< 30 mL/min/1.73m2,使用MDRD方法估计)的患者; 7. 已知6磷酸脱氢酶缺陷症的患者; 8. 近6个月有急性心肌梗死、或者不稳定性心绞痛、严重心律失常(多源频发室早、室速、室颤)等病史;纽约心功能分级(NYHA)III级-IV级。 9. QTc≥480ms; 10. 未纠正的低血钾症、低血镁症患者; 11. 已知患有精神类疾病的患者; 12. 胰腺炎患者; 13. 患有听觉受损的患者;; 14. 处于妊娠期、育龄女性妊娠试验阳性或哺乳期的女性患者; 15. 服用影响药物吸收、代谢和排泄的药物、可延长QTc间期的药物、可增加不良反应的药物等; 16. 研究者判断不适合参加本次临床试验者。 

Exclusion criteria:

1. Patients with identified allergies to 4-aminoquinoline and lopinavir/litonavir; 2. Patients with server diseases of the blood system; 3. Patients with identified severe liver disease, underlying cirrhosis or alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation more than 3 times the normal upper limit; 4. Patients with alcoholism or are taking hepatotoxic drugs; 5. Patients with renal impairment (estimated glomerular filtration rate [eGFR]< 30 mL/min/1.73m2, using the MDRD method); 6. Patients with 6-phosphate dehydrogenase deficiency; 7. History of acute myocardial infarction, unstable angina pectoris, severe arrhythmia (frequent ventricular, ventricular tachycardia, ventricular fibrillation) in recent 6 months; New York Heart Association (NYHA) level Ⅲ-Ⅳ; 8. QTc >= 480ms; 9. Uncorrected patients with hypokalemia or hypokalemia; 10. Patients with retinopathy, fundus lesions, macular degeneration; 11. Patients with psychiatric disorders; 12. Patients with pancreatitis; 13. Patients with server auditory damage; 14. Pregnant or breastfeeding women or female with positive pregnancy test at child-bearing age; 15. Patients with medication that affect drug absorption, metabolism and excretion, that can induce QT interval prolongation, or drugs that can increase adverse reactions, etc.; 16. Patients were not eligible for this trial based on Investigator's considerationsPatients with a history of malignant tumor in the last 5 years. 

研究实施时间:

Study execute time:

From2020-02-17To 2020-04-30 

征募观察对象时间:

Recruiting time:

From2020-02-17To 2020-04-30 

干预措施:

Interventions:

组别:

硫酸羟氯喹组

样本量:

50

Group:

hydroxychloroquine sulfate

Sample size:

干预措施:

Day 1:首剂600mg,间隔6h 600mg,共两次; Day 2-5:200mg,BID

干预措施代码:

Intervention:

Day1: first dose: 6 tablets(0.1g/table), second dose: 6 tablets (0.1g/table)after 6h ;Day2~5: 2 tablets (0.1g/table), BID

Intervention code:

组别:

磷酸氯喹组

样本量:

50

Group:

phosphate chloroquine

Sample size:

干预措施:

Day1-3:500mg,BID Day4-5:250mg,BID

干预措施代码:

Intervention:

Day1-3:500mg,BID Day4-5:250mg,BID

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同济医院 

单位级别:

三级 

Institution
hospital:

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

Level of the institution:

Tertiary A Hospital 

国家:

中国 

省(直辖市):

江西 

市(区县):

南昌 

Country:

China 

Province:

Jiangxi 

City:

Nanchang 

单位(医院):

南昌大学第一附属医院 

单位级别:

三级 

Institution
hospital:

The First Affiliated Hospital of Nanchang University  

Level of the institution:

Tertiary A Hospital 

国家:

中国 

省(直辖市):

北京 

市(区县):

 

Country:

China 

Province:

Beijing 

City:

 

单位(医院):

北京市海淀医院(北京大学第三医院海淀院区) 

单位级别:

三级 

Institution
hospital:

Beijing Haidian Hospital (Haidian Section of Peking University Third Hospital)  

Level of the institution:

Tertiary A Hospital 

测量指标:

Outcomes:

指标中文名:

临床恢复的时间

指标类型:

主要指标 

Outcome:

Time to Clinical Recovery, TTCR

Type:

Primary indicator 

测量时间点:

随机入组后28天内

测量方法:

Measure time point of outcome:

within 28 days after randomization

Measure method:

指标中文名:

28天的全因死亡率

指标类型:

次要指标 

Outcome:

All-cause mortality of 28-days

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

新型冠状病毒核酸检测转阴的时间

指标类型:

次要指标 

Outcome:

Transition time of 2019-nCoV nucleic acid detection

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

呼吸困难进展频率:SPO2≤94% 或者PaO2/FiO2<300mmHg,且需要额外供氧或气管插管/呼吸机支持

指标类型:

次要指标 

Outcome:

Frequency of respiratory progression:Defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

体温恢复正常的时间(天数)

指标类型:

次要指标 

Outcome:

Time to defervescence (days)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

达到轻度咳嗽或者无咳嗽症状的时间(天数)

指标类型:

次要指标 

Outcome:

Time to cough reported as mild or absen t(days)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

呼吸困难程度减轻或达到无呼吸困难症状的时间(天数)

指标类型:

次要指标 

Outcome:

Time to dyspnea reported as mild or absent (days)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

需要补充氧气或无创通气的时间(天数)

指标类型:

次要指标 

Outcome:

Time to requirement for supplemental oxygen or non-invasive ventilation (days)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

药效动力学指标

指标类型:

附加指标 

Outcome:

Pharmacodynamic index

Type:

Additional indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

安全性评价指标

指标类型:

附加指标 

Outcome:

safety index

Type:

Additional indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

免疫球蛋白:IgG、IgM

指标类型:

附加指标 

Outcome:

Immunoglobulin: IgG, IgM

Type:

Additional 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:

标本中文名:

咽拭子

组织:

Sample Name:

Troat swab

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):

中央随机

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

central randomization

盲法:

开放

Blinding:

open label

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):

发表文章

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

public article

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:

病例报告表

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

CRF

数据管理委员会:

Data Managemen Committee:

无/No

注册人:

Name of Registration:

 2020-02-16
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