ChiCTR2500100448 版本V1.0 版本创建时间2025/04/09 16:56:33 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：

ChiCTR2500100448 

最近更新日期：

Date of Last Refreshed on：

2025-04-09 16:56:14 

注册时间：

Date of Registration：

2025-04-09 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

增生型糖尿病视网膜病变微创玻璃体切割术前抗VEGF预处理的分子多组学与多模式影像学的关联研究

Public title：

Molecular multiomics and multimodal imaging study of anti-VEGF preconditioning before minimally invasive vitrectomy in proliferative diabetic retinopathy

注册题目简写：

PDR 晚期PPV术前法瑞西单抗预处理的综合疗效观察

English Acronym：

Comprehensive effect of pretreatment with farizumab before advanced PPV of PDR

研究课题的正式科学名称：

增生型糖尿病视网膜病变微创玻璃体切割术前抗VEGF预处理的分子多组学与多模式影像学的关联研究

Scientific title：

Molecular multiomics and multimodal imaging study of anti-VEGF preconditioning before minimally invasive vitrectomy in proliferative diabetic retinopathy

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：

黄玉娟 

研究负责人：

黄玉娟 

Applicant：

Yujuan Huang  

Study leader：

Yujuan Huang  

申请注册联系人电话：

Applicant telephone：

+86 158 2064 2880

研究负责人电话：

Study leader's telephone：

+86 158 2064 2880

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：

fs_sophia@126.com

研究负责人电子邮件：

Study leader's E-mail：

fs_sophia@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：

广东省佛山市禅城区卫国路78号佛山市第二人民医院1号楼9楼

研究负责人通讯地址：

广东省佛山市禅城区卫国路78号佛山市第二人民医院1号楼9楼

Applicant address：

9th Floor, Building 1, Foshan Second People's Hospital, No. 78 Weiguo Road, Chancheng District, Foshan City, Guangdong Province.

Study leader's address：

9th Floor, Building 1, Foshan Second People's Hospital, No. 78 Weiguo Road,Chancheng District, Foshan City, Guangdong 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：

佛山市第二人民医院

Applicant's institution：

Foshan Second People's Hospital

研究负责人所在单位：

佛山市第二人民医院

Affiliation of the Leader：

Foshan Second People's Hospital

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

批件(2024)-0052

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：

佛山市第二人民医院伦理委员会

Name of the ethic committee：

Ethics Committee of Foshan Second People's Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2024-07-23 00:00:00

伦理委员会联系人：

黄晓瑜

Contact Name of the ethic committee：

Xiaoyu Huang

伦理委员会联系地址：

广东省佛山市禅城区卫国路78号佛山市第二人民医院6号楼6楼

Contact Address of the ethic committee：

6th Floor, Building 6, Foshan Second People's Hospital, 78 Weiguo Road, Chancheng District, Foshan City, Guangdong Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 757 8803 2210

伦理委员会联系人邮箱：

Contact email of the ethic committee：

fseykjk@163.com

研究实施负责（组长）单位：

佛山市第二人民医院

Primary sponsor：

Foshan Second People's Hospital

研究实施负责（组长）单位地址：

广东省佛山市禅城区卫国路78号佛山市第二人民医院

Primary sponsor's address：

Foshan Second People's Hospital, No. 78 Weiguo Road, Chancheng District, Foshan City, Guangdong 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)：

广东省

市(区县)：

佛山

Country：

China

Province：

Guangdong

City：

Foshan

单位(医院)：

佛山市第二人民医院

具体地址：

广东省佛山市禅城区卫国路78号

Institution
hospital：

Foshan Second People's Hospital

Address：

No. 78 Weiguo Road, Chancheng District, Foshan City, Guangdong Province.

经费或物资来源：

医院科研基金

Source(s) of funding：

Hospital Research Fund

Target disease：

Diabetic Retinopathy

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：

4

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

本研究旨在探索增生型糖尿病视网膜病变（PDR）合并新生血管膜和（或）TRD和（或）难以吸收的玻璃体积血患者在玻璃体切割术（PPV）前接受抗血管内皮生长因子（VEGF）药物（法瑞西单抗）预处理的综合疗效。通过术前法瑞西单抗玻璃体腔内注射，减少术中出血、降低玻璃体视网膜界面牵拉程度，提高手术安全性和成功率，同时通过房水细胞因子检测，深入分析术前抗VEGF治疗对眼内微环境的调节作用，揭示其在视网膜病变治疗中的潜在机制，为优化PDR-TRD的临床治疗方案提供新的理论依据。  

Objectives of Study：

The objective of this study was to explore the combined efficacy of pre-treatment with an anti-vascular endothelial growth factor (VEGF) drug (pharizumab) prior to vitrectomy (PPV) in patients with proliferative diabetic retinopathy (PDR) with neovascular membranes and/or TRD and/or refractory vitreous hematoma. Intravitreous injection of pharizumab before surgery can reduce intraoperative bleeding, reduce the degree of vitreoretinal interface pulling, and improve surgical safety and success rate. Meanwhile, through the detection of aqueous aqueous cytokines, in-depth analysis of the regulatory effects of preoperative anti-VEGF treatment on the intraocular microenvironment is conducted to reveal its potential mechanism in the treatment of retinopathy. It provides a new theoretical basis for optimizing the clinical treatment of PDR-TRD.

药物成份或治疗方案详述：

药物名称：法瑞西单抗（Faricimab）或阿柏西普（Aflibercept：Eylea; Bayer, Leverkusen, Germany) 药物类别：抗血管内皮生长因子（抗VEGF）药物 药物成分：法瑞西单抗是一种双特异性单克隆抗体，可同时靶向血管内皮生长因子-A（VEGF-A）和血管生成素-2（Ang-2），通过抑制这两种因子的活性，减少病理性血管生成和血管渗漏。阿柏西普（Aflibercept：Eylea; Bayer, Leverkusen, Germany) 作为一种抗血管内皮生长因子（anti-VEGF）药物，是115 kDa的全人源重组融合蛋白，由 VEGFR1和VEGFR2的Ig结合结构域与人IgG的Fc区融合而成，不仅能结合 VEGF-A、VEGF-B，还能够结合PIGF，可有效抑制新生血管的形成和渗出，进而减轻视网膜水肿和出血，已被广泛应用于PDR的治疗中。 治疗方案： 给药方式：玻璃体腔内注射（Intravitreal Injection）。 给药剂量：每次注射剂量为6.0 mg（0.05 mL）。 给药时间：在玻璃体切割术（PPV）前7天进行单次注射。 术前准备：注射前需进行常规眼部消毒，并使用表面麻醉剂（如丙美卡因滴眼液）进行局部麻醉。 术后管理：注射后密切监测患者眼压及眼部反应，必要时给予降眼压药物或抗炎治疗。 治疗目标： 减少术中出血风险，改善手术视野清晰度。 降低玻璃体视网膜界面牵拉程度，提高手术安全性。 通过调节眼内微环境（如房水细胞因子水平），优化手术效果并促进术后恢复。 注意事项： 注射后需告知患者可能出现短暂的眼压升高、眼部不适或感染风险。 对于有严重全身或眼部感染、活动性眼内炎症或对药物成分过敏的患者，应谨慎使用或避免使用。 

Description for medicine or protocol of treatment in detail：

Drug name: Faricimab or Aflibercept Injections:(Aflibercept:Eylea; Bayer, Leverkusen, Germany) Drug category: Anti-vascular endothelial growth factor (anti-VEGF) drugs Pharmaceutical ingredients: Pharizumab is A bispecific monoclonal antibody that targets both vascular endothelial growth factor-A (VEGF-A) and angiogenin-2 (Ang-2), reducing pathologic angiogenesis and vascular leakage by inhibiting the activity of both factors. Aflibercept (Eylea; Bayer, Leverkusen, Germany), as an anti-vascular endothelial growth factor (anti-VEGF) drug, is a 115 kDa fully human recombinant fusion protein derived from the fusion of the Ig binding domain of VEGFR1 and VEGFR2 with the Fc region of human IgG. It can not only bind VEGF-A, VEGF-B, but also PIGF, which can effectively inhibit the formation and seepage of new blood vessels, and then reduce retinal edema and bleeding, and has been widely used in the treatment of PDR. Treatment options: Intravitreal Injection: intravitreal injection. Dose: 6.0 mg (0.05 mL) per injection. Time of administration: A single injection is given 7 days before vitrectomy (PPV). Preoperative preparation: Routine eye disinfection and local anesthesia with a topical anesthetic such as promecaine eye drops are required before injection. Postoperative management: Intraocular pressure and ocular reaction of patients were closely monitored after injection, and intraocular pressure-lowering drugs or anti-inflammatory therapy were given if necessary. Treatment goals: Reduce the risk of intraoperative bleeding and improve the clarity of surgical visual field. Reduce the degree of vitreoretinal interface pulling and improve surgical safety. By modulating the intraocular microenvironment (e.g., aqueous humor cytokine levels), surgical outcomes are optimized and postoperative recovery is facilitated. Note: After the injection, the patient should be informed of a possible temporary increase in eye pressure, eye discomfort, or risk of infection. It should be used with caution or avoided in patients with severe systemic or eye infections, active intraocular inflammation, or allergies to drug ingredients. 

纳入标准：

1.年龄在20-79岁成人糖尿病患者； 2.诊断为1型或2型糖尿病； 3.诊断为PDR合并新生血管膜和（或）TRD和（或）难以吸收的玻璃体积血，需要手术干预； 4.由于VH或因新生血管纤维血管膜无法完成PRP。 5.同意PDR玻璃体切割术前抗VEGF治疗。 6.参与者自愿参与本研究，并且有能力遵循研究计划和治疗方案，能够按时接受定期随访。

Inclusion criteria

1. Adult patients with diabetes aged 20-79; 2. Type 1 or type 2 diabetes; 3. Diagnosed with proliferative diabetic retinopathy (PDR) accompanied by neovascular membranes and/or TRD and/or refractory vitreous hematoma, requiring surgical intervention. 4. Inability to complete panretinal photocoagulation (PRP) due to vitreous hemorrhage (VH) or fibrovascular membranes from neovascularization. 5. Agreement to undergo anti-VEGF therapy prior to vitrectomy for PDR. 6. Participants must voluntarily agree to participate in the study, demonstrate the ability to comply with the study protocol and treatment plan, and commit to attending scheduled follow-up visits.

排除标准：

1.3个月内接受玻璃体腔内注射抗VEGF或视网膜激光光凝； 2.6个月内接受玻璃体腔内地塞米松注射或3个月内接受玻璃体腔内注射类固醇； 3.玻璃体切除史； 4.糖化血红蛋白（HbA1c）超过12%的DR患者； 5.排除因严重玻璃体积血无法用OCTA观察玻璃体视网膜交界面的PDR患者； 6.排除除PDR外，同时存在其他严重眼部疾病（如青光眼、 黄斑变性，其他视网膜血管疾病等）患者； 7.存在眼部感染和眼内炎症； 8.存在严重的系统性疾病，如未控制的糖尿病、未控制的高血压、6个月内心肌梗死或脑血管事故。 9.由于认知障碍、沟通困难或其他无法遵循治疗方案的患者。 10.对研究药物法瑞西单抗或阿柏西普药物存在过敏史的患者。

Exclusion criteria：

1. Patients who have received intravitreal anti-VEGF injections or retinal laser photocoagulation within the past 3 months. 2. Patients who have received intravitreal dexamethasone injections within the past 6 months or intravitreal steroid injections within the past 3 months. 3. Patients with a history of vitrectomy. 4. Diabetic retinopathy (DR) patients with a glycated hemoglobin (HbA1c) level exceeding 12%. 5. Patients with proliferative diabetic retinopathy (PDR) and severe vitreous hemorrhage that precludes observation of the vitreoretinal interface using optical coherence tomography angiography (OCTA). 6. Patients with concurrent severe ocular diseases other than PDR, such as glaucoma, macular degeneration, or other retinal vascular disorders. 7. Patients with active ocular infections or intraocular inflammation. 8. Patients with severe systemic conditions, including uncontrolled diabetes, uncontrolled hypertension, myocardial infarction within the past 6 months, or cerebrovascular accidents. 9. Patients with cognitive impairments, communication difficulties, or other conditions that may hinder adherence to the treatment protocol. 10. Patients with a known history of hypersensitivity to the study drugs, including aflibercept or faricimab or Aflibercept.

研究实施时间：

Study execute time：

从 From 2025-05-01 00:00:00至 To 2027-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-05-01 00:00:00 至 To 2027-12-31 00:00:00  

干预措施：

Interventions：

组别：

A组

样本量：

25

Group：

Group A

Sample size：

干预措施：

增生型糖尿病视网膜病变（PDR）伴牵拉性视网膜脱离（TRD）患者玻璃体切割术（PPV）前进行玻璃体腔内注射法瑞西单抗。

干预措施代码：

Intervention：

Patients with proliferative diabetic retinopathy (PDR) and tractional retinal detachment (TRD) were treated with intravitreal injection of faricizumab before vitrectomy (PPV)

Intervention code：

组别：

B组

样本量：

25

Group：

Group B

Sample size：

干预措施：

增生型糖尿病视网膜病变（PDR）伴牵拉性视网膜脱离（TRD）患者玻璃体切割术（PPV）前进行玻璃体腔内注射阿柏西普。

干预措施代码：

Intervention：

Patients with proliferative diabetic retinopathy (PDR) and tractional retinal detachment (TRD) were treated with intravitreal Aflibercept of faricizumab before vitrectomy (PPV)

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 广东省 

市(区县)：

 佛山市 

Country：

China 

Province：

Guangdong  

City：

Foshan 

单位(医院)：

佛山市第二人民医院 

单位级别：

三甲 

Institution
hospital：

Foshan Second People's Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

房水细胞因子（VEGF，IL-6，TNF-α，CTGF，PEDF、MCP-1，ICAM-1，VCAM-1，Ang2）

指标类型：

主要指标

Outcome：

Aqueous humor cytokines(VEGF,IL-6,TNF-α,CTGF,PEDFMCP-1,ICAM-1,VCAM-1,Ang2)

Type：

Primary indicator

测量时间点：

抗VEGF术前及术后7天（玻璃体切割术前）

测量方法：

Measure time point of outcome：

Anti VEGF preoperative and postoperative 7 days (before vitrectomy)

Measure method：

指标中文名：

玻璃体视网膜交界面血流

指标类型：

次要指标

Outcome：

Vitreoretinal junction blood flow

Type：

Secondary indicator

测量时间点：

PDR术前，术后1m、3m、6m

测量方法：

图湃OCTA

Measure time point of outcome：

Before PDR, 1m, 3m, 6m were performed after PDR

Measure method：

Tupai OCTA

指标中文名：

糖化血红蛋白

指标类型：

次要指标

Outcome：

Glycosylated hemoglobin

Type：

Secondary indicator

测量时间点：

抗VEGF术前

测量方法：

抽静脉血浆

Measure time point of outcome：

Anti-vegf preoperative

Measure method：

Intravenous plasma extraction

指标中文名：

视力

指标类型：

主要指标

Outcome：

vision acuity

Type：

Primary indicator

测量时间点：

PDR术前，术后1m、3m、6m

测量方法：

ETDRS视力表

Measure time point of outcome：

Before PDR, 1m, 3m, 6m were performed after PDR

Measure method：

ETDRS vision chart

指标中文名：

肾小球功能

指标类型：

次要指标

Outcome：

Glomerular function

Type：

Secondary indicator

测量时间点：

抗VEGF术前

测量方法：

抽静脉血浆

Measure time point of outcome：

Anti-vegf preoperative

Measure method：

Intravenous plasma extraction

指标中文名：

血肌酐

指标类型：

次要指标

Outcome：

Serum creatinine

Type：

Secondary indicator

测量时间点：

抗VEGF术前

测量方法：

抽静脉血浆

Measure time point of outcome：

Anti-vegf preoperative

Measure method：

Intravenous plasma extraction

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

房水

组织：

Sample Name：

Aqueous humor

Tissue：

人体标本去向

 使用后销毁  

说明

1年

Fate of sample：

Destruction after use  

Note：

1a

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 20 岁 years
最大 Max age 79 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）：

用计算机生成随机数（Excel表） 随机方法： 随机序列将通过计算机生成，由独立的统计学人员使用随机数字表法或计算机随机化程序生成。具体操作如下： 随机化方法：使用计算机程序（Excel）生成一个随机数序列。这些随机数序列将用于将参与者随机分配到不同的组（例如法瑞西单抗治疗组与阿柏西普对照组）。该程序将确保每位参与者有均等的机会被分配到任一组。 生成随机序列的人员：随机分配的任务将由独立的统计学人员进行，该人员与临床治疗团队没有直接接触，确保随机化过程的独立性和公正性。 随机化程序的透明性：生成的随机序列将在研究开始前由研究负责人和伦理委员会进行审核，以确保符合随机化原则并且保证分配过程的公平性。

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

Computer generated random numbers (Excel table) Random method: The random sequence will be generated by computer, either by an independent statistician using a random number table method or a computer randomization program. Specific operations are as follows: Randomization method: A computer program (Excel) is used to generate a random sequence of numbers. These random number sequences will be used to randomly assign participants to different groups (such as the farexizumab treatment group versus the arbocept control group). The procedure will ensure that each participant has an equal chance of being assigned to either group. The person who generates the random sequence: The randomly assigned task will be performed by an independent statistician who has no direct contact with the clinical treatment team, ensuring the independence and impartiality of the randomization process. Transparency of randomization procedures: The generated random sequences will be reviewed by the study leader and ethics Committee prior to the start of the study to ensure compliance with randomization principles and to ensure fairness in the allocation process.

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：

本研究采取双盲设计，所有患者在术前接受法瑞西单抗玻璃体腔内注射或安慰剂注射治疗时，患者及主治医生均对分配情况不知情。术后观察与数据记录由独立的研究人员进行，他们也对分组情况不知情，从而减少观察者偏倚。数据分析由专门的统计学人员进行，所有数据在分析时已去除患者分组信息，以确保分析结果的客观性。

Blinding：

In this study, a double-blind design was adopted. All patients received intravitreous injection or placebo injection before surgery, and neither the patients nor the attending physicians were aware of the allocation. Post-operative observations and data recording were performed by independent researchers who were also unaware of the grouping, thus reducing observer bias. Data analysis was performed by dedicated statisticians, and all data were analyzed without patient grouping information to ensure the objectivity of the analysis results.

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

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）：

采用临床试验公共管理平台，ResMan的网址是：www.medresman.org.cn。

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

A public clinical trial management platform, ResMan, ResMan can be found at www.medresman.org.cn.

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(Case Record Form, CRF)

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：

  2025-04-09 16:56:14