ChiCTR2200058633 版本V1.0 版本创建时间2022/12/16 14:53:54 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：

 ChiCTR2200058633 

最近更新日期：

Date of Last Refreshed on：

 2022-04-12 23:41:27 

注册时间：

Date of Registration：

 2022-04-12 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

信迪利单抗+贝伐珠单抗联合标准化疗二线治疗转移性结直肠癌的前瞻性、单臂、单中心临床研究

Public title：

A prospective, single-arm, single-center clinical study of Sintilizumab+bevacizumab combined with standard chemotherapy in the second-line treatment of metastatic colorectal cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

信迪利单抗+贝伐珠单抗联合标准化疗二线治疗转移性结直肠癌的前瞻性、单臂、单中心临床研究

Scientific title：

A prospective, single-arm, single-center clinical study of Sintilizumab and bevacizumab combined with standard chemotherapy in the second-line treatment of metastatic colorectal cancer

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：

马劼 

研究负责人：

马劼 

Applicant：

Ma Jie 

Study leader：

Ma Jie 

申请注册联系人电话：

Applicant telephone：

 +86 13978851892

研究负责人电话：

Study leader's
telephone：

+86 13978851892

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：

 majie086@163.com

研究负责人电子邮件：

Study leader's E-mail：

 majie086@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：

广西壮族自治区南宁市双拥路6号

研究负责人通讯地址：

广西壮族自治区南宁市双拥路6号

Applicant address：

6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, China

Study leader's address：

6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 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：

广西医科大学第一附属医院

Applicant's institution：

The First Affiliated Hospital of Guangxi Medical University

研究负责人所在单位：

广西医科大学第一附属医院

Affiliation of the Leader：

The First Affiliated Hospital of Guangxi Medical 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：

 ChiECRCT20220025

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：

中国注册临床试验伦理审查委员会

Name of the ethic committee：

Chinese Ethics Committee of Registering Clinical Trials

伦理委员会批准日期：

Date of approved by ethic committee：

 2022-03-02 00:00:00

伦理委员会联系人：

吴莼

Contact Name of the ethic committee：

Wu Chun

伦理委员会联系地址：

中国香港特别行政区九龙浸会大学道中国临床试验注册中心香港中心

Contact Address of the ethic committee：

Chinese Clinical trial Hong Kong Centre, Baptist University Road, Kowloon Tong, Hong Kong SAR, 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：

 chictr001@chictr.org.cn

研究实施负责（组长）单位：

广西医科大学第一附属医院

Primary sponsor：

The First Affiliated Hospital of Guangxi Medical University

研究实施负责（组长）单位地址：

广西壮族自治区南宁市双拥路6号

Primary sponsor's address：

6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 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)：

广西壮族自治区

市(区县)：

南宁

Country：

China

Province：

Guangxi Zhuang Autonomous Region

City：

Nanning

单位(医院)：

广西医科大学第一附属医院

具体地址：

广西壮族自治区南宁市双拥路6号

Institution
hospital：

The First Affiliated Hospital of Guangxi Medical University

Address：

6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region

经费或物资来源：

自筹经费

Source(s) of funding：

Self-financing

研究疾病：

结直肠癌  

Target disease：

Colorectal cancer

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：

 II期临床试验 

Study phase：

2

研究设计：

单臂 

Study design：

Single arm 

研究目的：

评价信迪利单抗（PD-1抗体）联合贝伐珠单抗+标准化疗二线治疗转移性结直肠癌的疗效和安全性。  

Objectives of Study：

To evaluate the efficacy and safety of Sintilizumab (PD-1 antibody) combined with bevacizumab + standard chemotherapy for second-line treatment of metastatic colorectal cancer.

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.在实施任何试验相关流程之前，签署书面知情同意；
2.年龄≥18周岁；
3.组织学或细胞学证实的无法手术的转移性直接肠癌（AJCC 8th为IV期）；
4.一线标准治疗期间或之后出现疾病进展（RECIST v1.1），一线标准方案可以为化疗±贝伐珠单抗/西妥昔单抗治疗；
5.根据实体肿瘤疗效评价标准（RECIST 1.1版），至少有一处影像学可测量病灶；
6.允许无症状或经局部治疗后症状稳定的脑转移患者入组，只要患者满足以下条件：
1)中枢神经系统之外有可测量病灶
2)无中枢神经系统症状或至少2周内症状无加重
3)无需糖皮质激素治疗或首次研究药物给药前7天内停用糖皮质激素治疗者
7.允许受试者接受姑息性放射治疗（包括针对症状性脑转移的颅脑放疗），但放疗需在入组前至少1周结束，并且放疗相关的毒性恢复至小于或等于1度（CTCAE 5.0，脱发除外）。
8.ECOG评分0-1分；
9.预期生存时间>3个月；
10.足够器官功能，受试者需满足如下实验室指标：
1)近14天未使用粒细胞集落刺激因子的情况下，中性粒细胞绝对值（ANC）≥1.5x109/L。
2)近14天未输血的情况下，血小板≥100×109/L。
3)近14天内无输血或使用促红细胞生成素的情况下，血红蛋白>9g/dL；
4)总胆红素≤1.5×正常值上限（ULN）；或总胆红素>ULN但直接胆红素≤ ULN
5)天门冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）在≤2.5×ULN（有肝转移的患者允许ALT 或AST ≤5×ULN）；
6)血肌酐≤1.5×ULN并且肌酐清除率（采用Cockcroft-Gault 公式计算）≥60 ml/min；
7)凝血功能良好，定义为国际标准化比值（INR）或凝血酶原时间（PT）≤1.5倍ULN；
8)甲状腺功能正常，定义为促甲状腺激素（TSH）在正常范围内。如基线TSH超出正常范围，如果总T3（或FT3）及FT4在正常范围内的受试者亦可入组；
9)心肌酶谱在正常范围内（如研究者综合判断为不具有临床意义的单纯实验室异常也允许入组）；（可选）
11.对于育龄期女性受试者，应在接受首次研究药物给药（第1周期第1天）之前的3天内接受尿液或血清妊娠试验且结果为阴性。如果尿液妊娠试验结果无法确认为阴性，则要求进行血液妊娠试验。非育龄期女性定义为绝经后至少１年，或进行过手术绝育或子宫切除术；
12.如存在受孕风险，所有受试者（不论男性或女性）均需在整个治疗期间直至治疗末次研究药物给药后120天（或末次化疗药物给药后180天）内采用年失败率低于1%的避孕措施；

Inclusion criteria

1. Sign written informed consent before implementing any test related process;
2. Aged >=18 years old;
3. Inoperable metastatic colorectal cancer confirmed by histology or cytology (AJCC 8th is stage IV);
4. If disease progression occurs during or after first-line standard treatment (RECIST v1.1), the first-line standard regimen can be chemotherapy ± bevacizumab / cetuximab;
5. According to the evaluation criteria of solid tumor efficacy (RECIST version 1.1), at least one imaging measurable lesion;
6. Patients with brain metastases who are asymptomatic or have stable symptoms after local treatment are allowed to be included as long as the patients meet the following conditions:
1) Measurable lesions outside the central nervous system
2) No central nervous system symptoms or no aggravation of symptoms for at least 2 weeks
3) Those who do not need glucocorticoid treatment or stop glucocorticoid treatment within 7 days before the administration of the first study drug
7. Subjects are allowed to receive palliative radiotherapy (including craniocerebral radiotherapy for symptomatic brain metastases), but the radiotherapy should be completed at least 1 week before enrollment, and the radiation-related toxicity should be restored to less than or equal to 1 degree (CTCAE 5.0, except hair loss);
8. ECoG score: 0-1;
9. Expected survival time > 3 months;
10. adequate organ function, subjects need to meet the following laboratory indicators:
1) The absolute value of neutrophils (ANC) >=1.5x10^9/l without granulocyte colony stimulating factor in recent 14 days.
2) Platelets >=90 without blood transfusion in recent 14 daysx10^9/L
3) Hemoglobin > 9g / dl without blood transfusion or erythropoietin in recent 14 days;
4) Total bilirubin <=1.5 ULN; or total bilirubin > ULN but direct bilirubin <= ULN;
5) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 ULN (ALT or AST <=ULN）
6) Blood creatinine <=1.5 ULN and creatinine clearance (calculated by Cockcroft Gault formula) >=60 ml / min;
7) Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) <=1.5 ULN;
8) Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH exceeds the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled;
9) The myocardial enzyme spectrum is within the normal range (if the researcher comprehensively judges that simple laboratory abnormalities without clinical significance are also allowed to be included in the group); (optional)
11. For female subjects of childbearing age, Urine or serum pregnancy test should be performed within 3 days before the first study drug administration (day 1 of cycle 1) and the result is negative. If the urine pregnancy test result cannot be confirmed as negative, blood pregnancy test is required. Women of non childbearing age are defined as at least 1 year after menopause, or have undergone surgical sterilization or hysterectomy;
If there is a risk of pregnancy, all subjects (male or female) are required to use contraceptives with an annual failure rate of less than 1% throughout the treatment period until 120 days after the last study drug administration (or 180 days after the last chemotherapy drug administration).

排除标准：

1.既往接受过下列疗法：抗PD1药物、抗PD-L1，抗PD-L2药物或者针对另一种刺激或协同抑制T细胞受体（例如，CTLA-4、OX-40、CD137）的药物（可调整）；
2.有症状或高风险的梗阻、出血、穿孔、肺炎（包括既往接受过激素治疗的非传染性肺炎和正在接受治疗的肺炎患者）等；
3.首次给药前5年内诊断为结直肠癌外的其他恶性疾病（不包括经过根治的皮肤基底细胞癌、皮肤鳞状上皮癌、和/或经过根治性切除的原位癌）；
4.当前正在参与干预性临床研究治疗，或在首次给药前4周内接受过其他研究药物或使用过研究器械治疗；
5.首次给药前2周内接受过具有抗肿瘤适应症的中成药或免疫调节作用的药物（包括胸腺肽、干扰素、白介素，除外为控制胸水局部使用）系统性全身治疗；
6.首次给药前2年内发生过需要全身性治疗（例如使用缓解疾病药物、糖皮质激素或免疫抑制剂）的活动性自身性免疫疾病。替代疗法（例如甲状腺素、胰岛素或者用于肾上腺或垂体机能不全的生理性糖皮质激素等）不视为全身性治疗；
7.研究首次给药前7天内正在接受全身性糖皮质激素治疗（不包括喷鼻、吸入性或其他途径的局部糖皮质激素）或任何其他形式的免疫抑制疗法；
注：允许使用生理剂量的糖皮质激素（≤10 mg/天的泼尼松或等效药物）；
8.首次治疗前7天内，接受输血；
9.存在临床上不可控制的胸腔积液/腹腔积液（不需要引流积液或停止引流3天积液无明显增加的患者可以入组）；
10.已知异体器官移植（角膜移植除外）或异体造血干细胞移植；
11.已知对本研究药物信迪利单抗、贝伐珠单抗活性成分或辅料过敏者;
12.具有影响口服药物的多种因素（比如无法吞咽、胃肠道切除术后、慢性腹泻和肠梗阻等）者；
13.在开始治疗前，尚未从任何干预措施引起的毒性和/或并发症中充分恢复（即，≤1级或达到基线，不包括乏力或脱发）；
14.已知人类免疫缺陷病毒（HIV）感染史（即HIV 1/2抗体阳性）；
15.未经治疗的活动性乙肝（定义为HBsAg阳性同时检测到HBV-DNA拷贝数大于所在研究中心检验科正常值上限）；
注：符合下列标准的乙肝受试者亦可入组：
1)首次给药前HBV病毒载量<1000拷贝/ml（200 IU/ml），受试者应在整个研究化疗药物治疗期间接受抗HBV治疗避免病毒再激活
2)对于抗HBc（+）、HBsAg（-）、抗HBs（-）和HBV病毒载量（-）的受试者，不需要接受预防性抗HBV治疗，但是需要密切监测病毒再激活
16.活动性的HCV感染受试者（HCV抗体阳性且HCV-RNA水平高于检测下限）；
17.首次给药之前（第 1 周期，第 1 天）30 天内接种过活疫苗；
注：允许首次给药前 30 天内接受针对季节性流感的注射用灭活病毒疫苗；但是不允许接受鼻内用药的减毒活流感疫苗。
18.妊娠或哺乳期妇女；
19.存在任何严重或不能控制的全身性疾病，例如：
1)静息心电图在节律、传导或形态上出现有重大且症状严重难以控制的异常，如完全性左束支传导阻滞，Ⅱ度以上心脏传导阻滞，室性心律失常或心房颤动；
2)不稳定型心绞痛，充血性心力衰竭，纽约心脏病协会（NYHA）分级≥ 2 级的慢性心衰；
3)在入选治疗前6个月内发生过任何动脉血栓、栓塞或缺血，如心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作等；
4)血压控制不理想（收缩压＞140 mmHg，舒张压＞90 mmHg）；
5)首次给药前1年内存在需要糖皮质激素治疗的非感染性肺炎病史，或当前存在临床活动性间质性肺病；
6)活动性肺结核；
7)存在需要全身性治疗的活动性或未能控制的感染；
8)存在临床活动性憩室炎、腹腔脓肿、胃肠道梗阻；
9)肝脏疾病如肝硬化、失代偿性肝病、急性或慢性活动性肝炎；
10)糖尿病控制不佳（空腹血糖（FBG）＞10mmol/L）；
11)尿常规提示尿蛋白≥++，且证实24小时尿蛋白定量＞1.0 g者；
12)存在精神障碍且无法配合治疗的患者；
有可能干扰试验结果、妨碍受试者全程参与研究的病史或疾病证据、治疗或实验室检查值异常，或研究者认为其他不适合入组的情况研究者认为存在其他潜在风险不适合参加本研究。

Exclusion criteria：

1. Have previously received the following therapies: anti-pd1 drugs, anti-PD-L1, anti-PD-L2 drugs or drugs that stimulate or co inhibit T cell receptors (e.g., CTLA-4, OX-40, CD137) (adjustable);
2. Symptomatic or high-risk obstruction, bleeding, perforation, pneumonia (including non communicable pneumonia previously treated with hormone and pneumonia patients being treated);
3. Other malignant diseases other than colorectal cancer diagnosed within 5 years before the first administration (excluding radical skin basal cell carcinoma, skin squamous epithelial carcinoma, and / or radical resection of carcinoma in situ);
4. Currently participating in intervention clinical research treatment, or receiving other research drugs or using research instruments within 4 weeks before the first administration;
5. Received systemic treatment with Chinese patent medicine with anti-tumor indications or drugs with immunomodulatory effect (including thymosin, interferon and interleukin, except for local use to control pleural effusion) within 2 weeks before the first administration;
6. Active autoimmune diseases requiring systemic treatment (such as disease relieving drugs, glucocorticoids or immunosuppressants) occurred within 2 years before the first administration. Alternative therapies (such as thyroxine, insulin or biological glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic treatment;
7. Being treated with systemic glucocorticoids (excluding local glucocorticoids by nasal spray, inhalation or other means) or any other form of immunosuppressive therapy within 7 days before the first administration of the study;
Note: it is allowed to use glucocorticoids in physiological doses (≤ 10 mg / day prednisone or equivalent);
8. Receive blood transfusion within 7 days before the first treatment;
9. There is clinically uncontrollable pleural effusion / peritoneal effusion (patients who do not need to drain effusion or stop drainage for 3 days and have no significant increase in effusion can be included in the group);
10. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
11. Those who are known to be allergic to the active ingredients or excipients of cindilimab and bevacizumab;
12. Those with multiple factors affecting oral drugs (such as inability to swallow, post gastrointestinal resection, chronic diarrhea and intestinal obstruction);
13. Not fully recovered from toxicity and / or complications caused by any intervention before starting treatment (i.e. <=grade 1 or reaching baseline, excluding fatigue or hair loss);
14. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1 / 2 antibody positive);
15. untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number at the same time was higher than the upper limit of normal value in the laboratory of the research center).
Note: hepatitis B patients who meet the following criteria can also be enrolled:
1) Before the first administration, the HBV viral load was less than 1000 copies / ml (200 IU / ml). Subjects should receive anti HBV treatment throughout the study chemotherapy treatment to avoid virus reactivation
2) For subjects with anti HBC (+), HBsAg (-), anti HBS (-) and HBV viral load (-), preventive anti HBV treatment is not required, but virus reactivation needs to be closely monitored
16. Active HCV infected subjects (HCV antibody positive and HCV-RNA level higher than the lower limit of detection);
17. Have received live vaccine within 30 days before the first administration (cycle 1, day 1);
Note: it is allowed to receive inactivated virus vaccine for injection against seasonal influenza within 30 days before the first administration; However, live attenuated influenza vaccines administered intranasal are not allowed.
18. Pregnant or lactating women;
19. There are any serious or uncontrollable systemic diseases, such as:
1) There are significant abnormalities in rhythm, conduction or morphology of resting ECG and the symptoms are serious and difficult to control, such as complete left bundle branch block, heart block above grade II, ventricular arrhythmia or atrial fibrillation;
2) Unstable angina pectoris, congestive heart failure, chronic heart failure with New York Heart Association (NYHA) grade >=2;
3) Any arterial thrombosis, embolism or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, occurred within 6 months before enrollment;
4) Poor blood pressure control (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg);
5) A history of noninfectious pneumonia requiring glucocorticoid treatment within 1 year before the first administration, or the current presence of clinically active interstitial lung disease;
6) Active pulmonary tuberculosis;
7) There are active or uncontrolled infections requiring systemic treatment;
8) There were clinically active diverticulitis, abdominal abscess and gastrointestinal obstruction;
9) Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
10) poor control of diabetes (fasting blood glucose (FBG) > 10mmol/L).
11) Urine routine examination showed that urinary protein >=+ +, and the 24-hour urinary protein was confirmed to be more than 1.0 G;
12) Patients with mental disorders and unable to cooperate with treatment;
Medical history or disease evidence, abnormal treatment or laboratory test values that may interfere with the test results, prevent the subjects from participating in the whole study, or other situations that the researchers believe are not suitable for inclusion. The researchers believe that there are other potential risks and are not suitable for participating in the study.

研究实施时间：

Study execute time：

从 From 2022-04-12 00:00:00至 To 2024-08-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2022-04-12 00:00:00 至 To 2023-08-31 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 30

Group：

test group

Sample size：

干预措施：

信迪利单抗联合贝伐珠单抗

干预措施代码：

Intervention：

Sintilizumab combined with bevacizumab

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中华人民共和国

省(直辖市)：

 广西壮族自治区 

市(区县)：

 南宁 

Country：

China

Province：

Guangxi

City：

Nanning

单位(医院)：

 广西医科大学第一附属医院 

单位级别：

 三甲 

Institution
hospital：

The First Affiliated Hospital of Guangxi Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

无疾病进展生存

指标类型：

主要指标

Outcome：

Disease-free survival

Type：

Primary 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

指标类型：

次要指标

Outcome：

Security

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

客观缓解率

指标类型：

次要指标

Outcome：

Objective response rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

疾病控制率

指标类型：

次要指标

Outcome：

Disease control rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

缓解持续时间

指标类型：

次要指标

Outcome：

Duration of remission

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总生存

指标类型：

次要指标

Outcome：

Overall survival

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：

外周血

Sample Name：

blood

Tissue：

Peripheral blood

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 18 岁 years
最大 Max age 75 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）：

非随机对照

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

Non-randomized control

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

否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）：

2024年12月，本网站，中国临床试验注册中心

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

Chinese clinical trial registry，December，2024

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：

所有统计分析将采用SAS 9.2（过更高版本）统计分析软件编程计算，所有的统计学检验均采用单侧0.05的优效性假设检验，组间比较将给出95%可信区间和p值。

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

All statistical analyses will be programmed by SAS 9.2 (higher version) statistical analysis software. All statistical tests will be performed with a one-side hypothesis test of 0.05 for superiority. 95% confidence intervals and P values will be given for comparison between groups.

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：

  2022-04-12 23:41:27