ChiCTR2300071620 版本V1.1 版本创建时间2023/07/20 20:08:55 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：

 ChiCTR2300071620 

最近更新日期：

Date of Last Refreshed on：

 2023-05-19 15:24:02 

注册时间：

Date of Registration：

 2023-05-19 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

免疫联合酪酸梭菌活菌片对照免疫单药用于广泛期小细胞肺癌患者一线治疗免疫维持阶段的随机、对照、开放、探索性临床研究

Public title：

Immunotherapy combined with Clostridium butyricum tablets compare with immunotherapy for first-line immune maintenance stage in extensive small-cell lung cancer, a randomized, controlled, open-label, exploratory clinical study.

注册题目简写：

English Acronym：

研究课题的正式科学名称：

免疫联合酪酸梭菌活菌片对照免疫单药用于广泛期小细胞肺癌患者一线治疗免疫维持阶段的随机、对照、开放、探索性临床研究

Scientific title：

Immunotherapy combined with Clostridium butyricum tablets compare with immunotherapy for first-line immune maintenance stage in extensive small-cell lung cancer, a randomized, controlled, open-label, exploratory clinical study.

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：

彭文颖 

研究负责人：

杨润祥 

Applicant：

WenYing Peng 

Study leader：

RunXiang Yang 

申请注册联系人电话：

Applicant telephone：

 +86 188 7422 3568

研究负责人电话：

Study leader's
telephone：

+86 1388876721

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：

 yrx_research@163.com

研究负责人电子邮件：

Study leader's E-mail：

 yrx_research@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：

云南省昆明市西山区昆州路519号云南省肿瘤医院

研究负责人通讯地址：

云南省昆明市西山区昆州路519号云南省肿瘤医院

Applicant address：

Yunnan Cancer Hospital, 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province

Study leader's address：

Yunnan Cancer Hospital, 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province

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：

云南省肿瘤医院

Applicant's institution：

Yunnan Cancer Hospital

研究负责人所在单位：

云南省肿瘤医院

Affiliation of the Leader：

Yunnan Cancer 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：

 YJZ2023-04

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：

云南省肿瘤医院伦理委员会

Name of the ethic committee：

Ethics Committee of Yunnan Cancer Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-04-11 00:00:00

伦理委员会联系人：

许玉玲

Contact Name of the ethic committee：

Yuling Xu

伦理委员会联系地址：

云南省昆明市昆州路519号云南省肿瘤医院伦理办公室

Contact Address of the ethic committee：

Ethics Office, Yunnan Cancer Hospital, 519 Kunzhou Road, Kunming City, Yunnan Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 871 6817 9625

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 ynzlyyll@163.com

研究实施负责（组长）单位：

云南省肿瘤医院

Primary sponsor：

Yunnan Cancer Hospital

研究实施负责（组长）单位地址：

云南省昆明市西山区昆州路519号云南省肿瘤医院

Primary sponsor's address：

Yunnan Cancer Hospital, 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

云南省

市(区县)：

昆明市

Country：

China

Province：

Yunnan Province

City：

Kuning City

单位(医院)：

云南省肿瘤医院

具体地址：

云南省昆明市西山区昆州路519号云南省肿瘤医院

Institution
hospital：

Yunnan Cancer Hospital

Address：

Yunnan Cancer Hospital, 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province

经费或物资来源：

科技人才与平台计划 （云南省院士专家工作站）项目编号：202205AF150027

Source(s) of funding：

Science and Technology Talents and Platform Program (Yunnan Academician Expert Workstation) Project No. : 202205AF150027

研究疾病：

肺恶性肿瘤  

Target disease：

Lung Neoplasm

研究疾病代码：

C34.900X001

Target disease code：

C34.900X001

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：

4

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

本研究为研究者发起研究，拟前瞻性入组最多120例经4周期含铂双药化疗，且其中至少2周期免疫联合含铂双药方案化疗后，末次疗效评估为疾病控制（SD，PR，CR）的广泛期小细胞肺癌患者。受试者随机分为两组，研究过程中将进行适应性随机（adaptive randomization），试验组以口服酪酸梭菌活菌片与免疫检查点抑制剂静脉滴注联合维持治疗，对照组以免疫检查点抑制剂单药静脉滴注维持治疗，评估试验组方案的有效性及安全性。 主要研究终点：无进展生存时间（PFS）； 次要研究终点：缓解持续时间（DoR）、总生存时间（OS），治疗的安全性。 探索性目的：评估肠道微生物的菌群状态、外周血中生物标志物等在用药前后的变化，及其与SCLC免疫治疗预后的相关性。  

Objectives of Study：

This study is a investigator-initiated study (ITT) and plan to prospectively enroll at most 120 extensive small-cell lung cancer (SCLC) patients who received 4 cycles of platinum based doublet-chemotherapy,(including at least 2 cycle ICIs plus chemotherapy) and was assessed as disease control (stable disease, partial remission, complete remission). The subjects will be randomly assigned to experimental or control group through adaptive randomization, and the Experimental group will recieve oral Clostridium butyricum tablets combined with immune checkpoint inhibitor while the control group will receive immune checkpoint inhibitor only. Primary end points of this study is progression-free survival (PFS), secondary end points are duration of response (DoR) , overall survival (OS) , and safety of treatment. This study will also evaluate the changes of intestinal microflora and biomarkers in peripheral blood before and after treatment, and the correlation of these biomarkers with the prognosis of SCLC immunotherapy.

药物成份或治疗方案详述：

药物成分：酪酸梭菌（Clostridium butyricum，MIYAIRI 588（CBM588，MIYA-BM?）是从土壤中分离得到的益生菌，属于非处方药品，酪酸梭菌 （C. butyricum） 是一种产生丁酸酯、形成孢子的厌氧菌，存在于健康的人类和动物肠道中，也存在于环境中，包括土壤和蔬菜中。 治疗方案：本实验为探索性开放标签、随机对照临床试验，研究将受试者根据前期疗效分析结果适应性随机至两组，试验组为维持治疗阶段应用口服酪酸梭菌活菌片联合免疫检查点抑制剂，对照组为仅使用免疫检查点抑制剂。酪酸梭菌活菌片为持续用药，免疫检查点抑制剂根据说明书用药，一般每21天用药一次。目前已获批的一线治疗广泛期小细胞肺癌的免疫检查点抑制剂为：阿替利珠单抗注射液（Atezolizumab）、度伐利尤单抗注射液（Durvalumab）、阿得贝利单抗注射液（Adebrelimab）、斯鲁利单抗（Serplulimab），包括但不限于以上。 

Description for medicine or protocol of treatment in detail：

Clostridium butyricum, also called MIYAIRI 588 (CBM588, MIYA-BM) is a Probiotic isolated from soil which belongs to over-the-counter medicine. Clostridium butyricum (C. butyricum) is a kind of anaerobic bacteria producing butyrate and forming spores, which also habitate in healthy human and animal intestines as well as the nature environment, such as soil and vegetables. research approach: This is an exploratory open-label randomized controlled clinical trial. Subjects will be randomly assigned to two groups based on the results of preliminary efficacy analysis. The experimental group received oral Clostridium butyricum tablets combined with immune checkpoint inhibitor maintenance therapy, while the control group will receive immune checkpoint inhibitor only. Clostridium butyricum tablets will be prescribed everyday, and immune checkpoint inhibitors will be administered according to the instructions, usually once every 21 days. Currently approved first-line immune checkpoint inhibitors for the first-line treatment of extensive small cell lung cancer including but not limited to: Atezolizumab, Durvalumab, Adebrelimab and Serplulimab. 

纳入标准：

1、男性或女性，18岁（含）以上；
2、患者体能状态评分（ECOG）在0-2分；
3、预期生存期大于12周；
4、组织学或细胞学确诊的转移性或广泛期的小细胞肺癌 (SCLC)后，经过含铂双药化疗4周期，其中免疫检查点抑制剂联合化疗至少2周期。并且受试者在末次治疗后影像学（RECIST1.1标准）评估为疾病稳定（SD），部分缓解（PR）或完全缓解（CR）。（所用免疫检查点抑制剂为NCCN、ESMO、CSCO指南中推荐使用于广泛期SCLC的免疫检查点抑制剂，包括但不限于：度伐利尤单抗、阿替利珠单抗、斯鲁利单抗、阿德贝利单抗等）。
5、局限期SCLC在经标准同步放化疗后，若敏感复发（距离一线治疗结束大于6个月后复发）进展为广泛期，且符合入组条件第4，可入组本研究。
6、对于既往按疗程规律服用过说明书中明确有抗肿瘤作用的中成药物，需至少洗脱2周后随机。
7、患者在RECIST1.1标准下至少有1个可评估的靶病灶（非颅内病灶）；
8、能够吞咽口服药物；
9、血常规：中性粒细胞绝对计数（ANC）≥1.5×109/L或白细胞计数>3.5×109/L，血小板（PLT）≥80×109/L，血红蛋白（HGB）≥90 g/L；
10、肝功能：血清总胆红素（TBIL）≤1.5 倍正常上限（ULN），丙氨酸氨基转移酶（ALT）和/或天门冬氨酸氨基转移酶（AST）≤2.5倍ULN，血清白蛋白（ALB）≥2.8g/dL；
11肾功能：血清肌酐（Cr）≤1.5×ULN，或肌酐清除率≥40 mL/min（应用标准的 Cockcroft；-Gault 公式）：
女性： CrCl=[（140-岁数） × 体重（kg） × 0.85]/[72 × 血清肌酐（mg/dL）]
男性： CrCl=[（140-岁数）× 体重（kg）×1.00]/[72 × 血清肌酐（mg/dL）]
12、受试者与受试者性伴侣需要在研究治疗期间和研究治疗期结束后 6 个月内采用至少一种经医学认可的避孕措施（如宫内节育器，避孕药或避孕套等） ；
13、受试者在进行本研究相关治疗、采样（外周血及大便）分析前，充分理解、配合，并已取得受试者签名并注明日期的书面知情同意书。

Inclusion criteria

1. Male or female, above 18 years old (including);
2. The patient's ECOG score should be 0-2;
3. The expected survival time is greater than 12 weeks.
4. After histologically or cytologically confirmed metastatic or extensive small cell lung cancer (SCLC), four cycles ofplatinum based doublet-chemotherapy, including at least two cycles of immune checkpoint inhibitor combined with chemotherapy were performed. Subjects were radiologically assessed (RECIST1.1 criteria) as stable disease (SD), partial remission (PR), or complete remission (CR) after the last treatment. (The immune checkpoint inhibitor used were NCCN, ESMO, and CSCO guidelines recommended for extensive SCLC, including but not limited to: Duvaliumab, atrilizumab, Srulizumab, Addebiliumab, etc.).
5. Limited stage SCLC can be enrolled in this study if evaluated chemo-sensitive (relapsed more than 6 months after the end of first-line treatment) when progresses as extensive stage after standard concurrent chemoradiotherapy and meets the 4th inclusion condition.
6. Patients regularly received anti-tumor Chinese patent medicine should be eluted for at least 2 weeks before randomized.
7. There is at least one evaluable lesion (non-intracranial lesion) under RECIST1.1 criteria;
8. Able to swallow pills;
9.blood routine examination: Absolute neutrophil count (ANC) ≥1.5×109/L or White blood cell count >3.5×109/L, platelet (PLT) ≥80×109/L, hemoglobin (HGB) ≥90 g/L;
10. Liver function: serum total bilirubin (TBIL) ≤1.5 times of the upper limit of normal (ULN), alanine aminotransferase (ALT) and/or Aspertate Aminotransferase (AST) ≤2.5 times ULN, serum albumin (ALB) ≥2.8g/dL;
11. Kidney function: serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance rate≥40 mL/min (standard Cockcroft; -Gault formula)
For females: CrCl=[(140-age) × weight (kg) × 0.85]/[72 × serum creatinine (mg/dL)]
For males: CrCl=[(140-age) × weight (kg) ×1.00]/[72 × serum creatinine (mg/dL)]
12. The subjects and his/her couple are required to use at least one medical approved contraceptive measures (e.g. intrauterine device, contraceptive pill or condom) during the study treatment period and 6 months after the end of study treatment.
13. Before the treatment and sampling (peripheral blood and Defecate) analysis related to this study, the subject can fully understand and cooperate, then an informed consent should be signed.

排除标准：

1.筛选期和既往影像学评估经CT扫描或MRI检测发现发现活动性或未治疗的CNS转移，既往接受过治疗的无症状CNS转移的患者只要符合下列所有标准，即可参与本研究：仅有幕上和小脑转移（即，中脑、延桥、延髓或脊髓不能有转移）；无需使用皮质类固醇治疗CNS疾病，在CNS定向治疗结束后至筛选期时影像学检查未发现进展；如果在筛选期影像发现患者出现新的无症状CNS转移，则必须接受放射治疗和/或CNS转移灶手术。
2. 手术和/或放疗治疗未能缓解的脊髓压迫，或既往诊断的脊髓压迫经治疗后没有临床证据显示在治疗期前疾病稳定≥1周；
3. 有临床症状的第三间隙积液需要反复引流（如少于4周1次），如经抽水或其他治疗仍无法控制的心包积液、胸腔积液和腹腔积液；
4. 首剂用药前≤5年并发其他恶性肿瘤，充分治疗的宫颈原位癌、基底细胞或鳞状上皮细胞皮肤癌、根治术后的局部前列腺癌、根治术后的导管原位癌除外（允许非转移性前列腺癌或乳腺癌的内分泌治疗）；
5. 活动性、己知或怀疑自身免疫性疾病（入选前可能存在的自身免疫疾病）包括但不仅限于重症肌无力、自身免疫性肝炎、系统性红斑狼疮、类风湿性关节炎、炎性肠病等。
(1）允许1型糖尿病（通过胰岛素治疗血糖得以控制）、仅需要激素替代疗法治疗的因自身免疫性甲状腺炎导致的残留甲状腺功能减退，或缺乏外因刺激的情况下预期不会复发的情况可以入组；
(2）患有湿疹、牛皮癣、慢性单纯性苔藓或仅有白癜风皮肤病表现的患者（需排除银屑病性头节炎）如果皮疹覆盖面积小于体表面积10%，基线时疾病已充分控制且仅需要低效价的局部类固醇治疗，过去12个月内基础疾病未出现急性加重（不需要补骨脂素加紫外线福射[PUVA]、甲氨蝶呤、类视黄醇、生物制剂、口服钙调磷脂酶抑制剂，高效价口服类固醇）则可以进入研究：
6. HBsAb阳性且HIV DNA拷贝数大于1000拷贝数/ml或200 IU/ml，或HCV阳性 (HCV RNA或HCV Ab检测提示急慢性感染）或已知HIV阳性病史或己知的获得性免疫缺陷综合征 (Acquired Immunodeficiency Syndrome, AIDs)；HCV阳性 (HCV RNA或HCV Ab检测提示急慢性感染）者控制后可入组。
7. 患有特发性肺纤维化病史、机化性肺炎（如阻塞性细支气管炎）、药物诱导的肺炎、 需要类固醇治疗的放射性肺炎或有临床症状的活动性肺炎：或其他严重影响肺功能的中重度肺部疾病（放射区存在放射性肺炎（纤维化）病史的患者可参加本研究）；
8. 活动性肺结核（tuberculosis,TB）或筛选前≤48周内有活动性肺结核感染病史的受试者，无论是否治疗；
9. 在开始研究药物治疗前7天内，具有需要静脉治疗的活动性病毒、细菌或全身性真菌感染的证据。需要任何全身性抗病毒药物、抗真菌药物或抗细菌药物治疗的活动性感染患者必须在开始研究药物治疗前至少一周完成治疗；
10. 在筛选期前28天内接受过大型手术，或计划在研究期间接受大型手术；
11. 筛选期前28天内使用减毒活疫苗，或预计研究期间需要使用此种减毒活疫苗，灭活CoVID-19疫苗可以入组。
12. 有严重的心血管疾病如心力衰竭、不稳定型心绞痛、不稳定性心律失常、未控制的高血压，筛选期前 6个月内发生的心肌梗死或脑血管意外；
13. 既往接受过同种异体骨髓移植或实体器官移植的患者；
14. 已知有精神疾病、酗酒、无法戒烟、吸毒或药物滥用等情况；
15. 经研究者判断，受试者有其他可能导致本研究被迫中途终止的因素，如：不依从方案、其他的严重疾病（含精神疾病）需要合并治疗、有严重的实验室检查异常、伴有家庭或社会等因素、会影响到受试者的安全、或资料及样品的收集。

Exclusion criteria：

1. Patients with active or untreated CNS metastases found by CT scan or MRI during screening and prior radiographic evaluation, and asymptomatic CNS metastases who have previously received treatment, may participate in this study if all of the following criteria are met:① only supratentorial and cerebellar metastases (no metastases from the midbrain, oblongata, medulla oblongata, or spinal cord); ②the CNS disease do not need corticosteroids and there was no evidence of progression on imaging between the end of stereotactic radiotherapy and screening; ③ If new asymptomatic CNS metastases was found on screening period, radiation therapy and/or CNS metastases surgery must be performed.
2. Spinal compression that cannot be relieved by surgery and/or radiotherapy, or previously diagnosed spinal compression after treatment without clinical evidence showing stable disease for ≥ 1 week before the treatment period;
3. The third space effusion with clinical symptoms needs repeated drainage (for example, once less than 4 weeks), such as pericardial effusion, pleural effusion and peritoneal effusion that cannot be controlled after thoracentesis or other treatments;
4. Other malignant tumors diagnosed ≤5 years before the first dose, except for adequately treated carcinoma in situ of cervix, basal cell or squamous cell skin cancer, local prostate cancer after radical mastectomy, and ductal carcinoma in situ after radical mastectomy ( Endocrine therapy for non-metastatic prostate or breast cancer is allowed);
5. Active, known or suspected autoimmune diseases (autoimmune diseases that may exist before enrollment), including but not limited to myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease etc.
(1) Type 1 diabetes mellitus (glycemic control with insulin therapy), residual hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement therapy, or no replase expected in the absence of external stimulus are allowed;
(2) Patients with eczema, psoriasis, lichen simplex chronicus or only skin disease manifestations of vitiligo (psoriatic head arthritis needs to be excluded) if the rash covers area less than 10% of the body surface area, the disease has been adequately controlled at baseline and requires only low potency topical steroids with no acute exacerbations of underlying disease within past 12 months (no psoralen plus ultraviolet radiation [PUVA], methotrexate, retinoids, biologics, oral calcineurin inhibitors, high potency oral steroids) can enter the study:
6. HBsAb positive and HIV DNA copy number greater than 1000 copy number/ml or 200 IU/ml, or HCV positive (HCV RNA or HCV Ab detection indicates acute and chronic infection) or known HIV positive medical history or known Acquired Immunodeficiency Syndrome (Acquired Immunodeficiency Syndrome, AIDs); HCV positive (HCV RNA or HCV Ab detection indicates acute and chronic infection) can be enrolled after control.
7. Patients with a history of idiopathic pulmonary fibrosis, organizing pneumonia (such as obstructive bronchiolitis), drug-induced pneumonia, radiation-related pneumonitis requiring steroid therapy, or active pneumonia with clinical symptoms, or other moderate to severe lung disease seriously affect pulmonary function (patients with a history of radiation pneumonitis (fibrosis) limited in the radiation area can participate in this study);
8. Subjects with active tuberculosis (tuberculosis, TB) or a history of active tuberculosis infection within 48 weeks before screening, regardless of treatment or not;
9. Evidence of active viral, bacterial or systemic fungal infection requiring intravenous therapy within 7 days prior to initiation of study drug treatment. Patients with active infection requiring any systemic antiviral, antifungal, or antibacterial drug treatment must end at least one week before starting study drug treatment;
10. Received major surgery within 28 days before the screening period, or plan to undergo major surgery during the study period;
11. The attenuated live vaccine was used within 28 days before the screening period, or the live attenuated vaccine is expected to be used during the study period, while receiving inactivated CoVID-19 vaccine can be included in the group.
12. Have serious cardiovascular diseases such as heart failure, unstable angina, unstable arrhythmia, uncontrolled hypertension, myocardial infarction or cerebrovascular accident within 6 months before the screening period;
13. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation;
14. Known mental illness, binge drinking, inability to quit smoking, take drugs or substance abuse;
15. According to the investigator's judgment, the subject has other factors that may cause the study to be terminated midway, such as: non-compliance with the protocol, other serious diseases (including mental diseases) requiring combined treatment, severe laboratory test abnormalities, accompanied by factors such as family or society, which will affect the safety of the subjects, or the collection of data and samples.

研究实施时间：

Study execute time：

从 From 2023-06-01 00:00:00至 To 2025-06-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-06-01 00:00:00 至 To 2025-06-01 00:00:00

干预措施：

Interventions：

组别：

对照组

样本量：

 60

Group：

Control group

Sample size：

干预措施：

免疫检查点抑制剂治疗

干预措施代码：

 control

Intervention：

immune checkpoint inhibitors

Intervention code：

组别：

实验组

样本量：

 60

Group：

Experimental group

Sample size：

干预措施：

免疫检查点抑制剂维持阶段联合酪酸梭菌活菌片

干预措施代码：

 experimental

Intervention：

Immune checkpoint inhibitor combined with Clostridium butyricum tablets at maintenance phase

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 云南省 

市(区县)：

 昆明市 

Country：

China

Province：

Yunnan Province

City：

Kunming City

单位(医院)：

 云南省肿瘤医院 

单位级别：

 三甲 

Institution
hospital：

Yunnan Cancer Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

无进展生存期

指标类型：

主要指标

Outcome：

Progression-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：

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：

总生存时间

指标类型：

次要指标

Outcome：

Overall survival 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：

安全性

指标类型：

次要指标

Outcome：

safety

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：

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：

粪便

组织：

Sample Name：

excrement

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 18 岁 years
最大 Max age 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）：

本研究采用疗效适应性(response-adaptive)随机方法，根据患者特征将患者分配到对照组或者试验组治疗。即当患者进入临床试验时，观察患者特定特征（也称为协变量）如：年龄、性别等，连同病人以前的信息来制定患者的治疗，这个过程通过R语言实现。随着治疗信息的积累，每种治疗对下一个患者产生成功结果的估计变得更加确定，越来越多的患者进入临床试验，患者获得“更佳”治疗可能性更大，获得“更糟”治疗可能性更小。

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

This study used Response-adaptive clinical trials in which patients were assigned to the control group or the experimental group for treatment according to the characteristics of patients. That is, when a patient enters a clinical trial, specific characteristics (also known as covariates) of the patient, such as age and gender, are observed together with the patient's previous information to formulate the patient's treatment. This process is realized through R language. As treatment information accumulates, the estimate of successful outcomes for the next patient for each treatment becomes more certain, more patients enter clinical trials, and patients are more likely to receive "better" treatment and less likely to receive "worse" treatment.

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：

无

Blinding：

None

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）：

NA

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

NA

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：

NA

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

NA

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：

  2023-05-19 15:23:13