医疗器械临床试验方案
Medical device clinical trial protocol

方案编号：YNCXQ-20240820
Scheme number: YNCXQ-20240820

一次性使用凝胶补片成型器临床使用的安全性和有效性的前瞻性、多中心、随机、平行对照、优效性临床试验方案
A prospective, multicenter, randomized, parallel-controlled, superiority clinical trial plan for the safety and efficacy of single-use gel patch formers for clinical use

试验医疗器械名称：一次性使用凝胶补片成型器
Name of the test medical device: Disposable gel patch former

型号规格：YN-PAT 35
Model specification: YN-PAT 35

需进行临床试验审批的第三类医疗器械 是□ 否R
The third type of medical device that needs to be approved for clinical trials is □ No R

方案版本号和日期：V4.0 2025年3月17日
Solution version number and date: V 4.0 March 17, 2025

临床试验机构：浙江大学医学院附属邵逸夫医院
Clinical trial institution: Run Shaw Hospital Affiliated to Zhejiang University School of Medicine

主要研究者：王强
Principal investigator: Wang Qiang

临床试验组长单位/协调研究者（多中心临床试验适用）：王强
Clinical trial team leader unit/coordinating investigator (for multicenter clinical trials): Wang Qiang

申办者：杭州源囊生物科技有限公司
Sponsor: Hangzhou Yuannang Biotechnology Co., Ltd

签字页-主要研究者
Signature Page - Principal Investigator

临床试验题目：一次性使用凝胶补片成型器临床使用的安全性和有效性的前瞻性、多中心、随机、平行对照、优效性临床试验临床试验方案
Clinical trial title: Prospective, multicenter, randomized, parallel-controlled, superiority clinical trial clinical trial protocol for the safety and efficacy of single-use gel patch formers for clinical use

方案版本号和日期：V4.0 2025年1月2日
Solution version number and date: V 4.0 January 2, 2025

研究中心名称：浙江大学医学院附属邵逸夫医院
Research Center Name: Run Shaw Hospital, Zhejiang University School of Medicine

研究中心编号：01
Research center number: 01

我是以下签字者，我负责主持在本中心开展此临床试验。我将根据 GCP 的规定，认真履行研究者职责。我证实我理解并且将遵循本临床试验方案、任何批准的试验方案修订、我国 GCP、ICH-GCP 和所有适用的国家法律法规和药品监督管理部门要求开展本次临床试验。我将负责做出与临床试验相关的医疗决定，保证受试者在试验期间出现不良事件时及时得到适合的医疗处理。我保证真实、准确、完整、及时、合法地记录数据。我将接受申办者委派的监查员或稽查员的监查或稽查及药品监督管理部门的稽查和视察，确保临床试验的质量符合要求。
I am the signatory of the following and I am responsible for presiding over this clinical trial at our center. I will perform my duties as a researcher diligently in accordance with GCP regulations. I confirm that I understand and will follow this clinical trial protocol, any approved trial protocol amendments, our country GCP, ICH-GCP and all applicable national laws and regulations and drug regulatory authorities require this clinical trial to be carried out. I will be responsible for making medical decisions related to clinical trials and ensuring that subjects receive appropriate medical management in the event of adverse events during the trial. I guarantee that the data will be recorded truthfully, accurately, completely, timely, and legally. I will accept the supervision or inspection of the supervisor or inspector appointed by the sponsor and the inspection and inspection by the drug administration department to ensure that the quality of the clinical trial meets the requirements.

签名：              日期：
Signature: Date:

保密声明
Confidentiality Statement

本方案中所包含的所有信息的所有权归杭州源囊生物科技有限公司，因此仅提供给研究者、合作研究者、伦理委员会和监督管理部门等相关的医疗机构审阅。在未得到杭州源囊生物科技有限公司书面的批准情况下，除了在与可能参加本研究的受试者签署知情同意书时，向其做必要的解释外，严禁将任何信息告知与本研究无关的第三方。
All information contained in this protocol belongs to Hangzhou Yuannang Biotechnology Co., Ltd., so it is only provided to relevant medical institutions such as researchers, collaborating investigators, ethics committees, and regulatory authorities. Without the written approval of Hangzhou Yuansang Biotechnology Co., Ltd., it is strictly forbidden to inform any information to third parties unrelated to this study, except for the necessary explanation when signing the informed consent form with subjects who may participate in this study.

一、申办者信息
1. Applicant information

（一）申办者名称
(1) Name of the applicant

杭州源囊生物科技有限公司
Hangzhou Yuansang Biotechnology Co., Ltd

（二）申办者地址
(2) The address of the applicant

杭州市萧山区明星路371号杭州湾信息港二幢连廊 8楼803室
Room 803, 8th Floor, Corridor of Hangzhou Bay Information Port Building 2, No. 371 Xingxing Road, Xiaoshan District, Hangzhou

（三）申办者联系方式
(3) Contact information of the applicant

联系人：杨丹
Contact: Yang Dan

联系电话：0571-88313603
Contact number: 0571-88313603

二、临床试验机构和主要研究者信息
2. Information on clinical trial institutions and principal investigators

初步确定的临床试验机构和研究者信息见表1，若试验期间临床试验机构和研究者发生变化，每次改动可无需采用正式修正方案的方式更新名单，不更改方案版本号和版本日期，可由牵头单位保存变更备案，申办者留存一份更新名单，在需要时提供。最终的临床总结报告中提供所有临床试验机构和研究者的最终名单。
If the clinical trial institution and investigator change during the trial, each change can be updated without the formal revision of the plan, and the version number and version date of the protocol can be saved by the lead unit, and the sponsor will keep an updated list and provide it when needed. A final list of all clinical trial sites and investigators is provided in the final clinical summary report.

表1临床试验机构和研究者信息列表
Table 1 List of clinical trial institutions and investigators

三、临床试验的背景资料
3. Background information of clinical trials

（一）研发背景
(1) R&D background

数千年来，增强伤口组织愈合一直是医生的目标。随着中国加速进入老年化社会，创伤护理市场快速增长。很多患者，尤其是患有基础病的老年人受伤后，伤口未及时修复，容易发展成慢性创面，面临坏疽、截肢等风险。难愈性创面的治疗是一个持续存在的医疗问题，在中国，数千万患者饱受难愈性创面的折磨。以糖尿病足溃疡（Diabetic foot ulcer，DFU）为例，其治疗费用占糖尿病治疗总费用的25-50%。其中5%-8%的DFU的患者在第1年需要截肢，且截肢后5年约有45%-55%的患者死亡。难愈性创面已经成为一个患病群体基数大，急需解决的健康问题。
Enhancing wound tissue healing has been the goal of doctors for thousands of years. As China accelerates into an aging society, the trauma care market is growing rapidly. Many patients, especially the elderly with underlying diseases, are not repaired in time after injury, and are prone to develop into chronic wounds and face risks such as gangrene and amputation. Treatment of refractory wounds is an ongoing medical problem, with tens of millions of patients suffering from refractory wounds in China. Taking diabetic foot ulcer (DFU) as an example, its treatment cost accounts for 25-50% of the total cost of diabetes treatment. Among them, 5%-8% of DFU patients require amputation in the first year, and about 45%-55% of patients die 5 years after amputation. Refractory wounds have become a health problem with a large base of patients and urgently need to be solved.

目前难愈性创面的治疗方法主要包括坏死组织清创、感染控制、血运重建、局部减压和合并症治疗等。然而，这些治疗策略通常需要同时进行，并导致巨大的治疗成本和复杂性。为了改善难愈创面组织愈合，国际上一些公司开发了许多类型的新技术和促再生敷料产品，包括生长因子输送、基因治疗等。但由于难愈性创面的复杂性，不同的个体具有不同的生化特征，补充单一的生长因子或仅针对单一的基因难以达到理想的伤口愈合，且部分先进治疗方法存在未知风险。所以在国内这些治疗方法也未正式获得批准。自体PRP作为一种再生修复治疗方法，已在国内被广泛应用于骨折术后修复。国内外存在大量的临床研究证实自体PRP可以有效促进创面愈合。作为一种便捷无痛苦低风险的治疗手段，且富含大量生长因子，治疗效果显著，自体PRP治疗被广泛患者所接受。
At present, the treatment methods of refractory wounds mainly include necrotic tissue debridement, infection control, revascularization, local decompression and comorbidity treatment. However, these treatment strategies often need to be performed simultaneously and lead to significant treatment costs and complexities. In order to improve the healing of intractable wound tissue, some international companies have developed many types of new technologies and regenerative dressing products, including growth factor delivery, gene therapy, etc. However, due to the complexity of refractory wounds, different individuals have different biochemical characteristics, and it is difficult to achieve ideal wound healing by supplementing a single growth factor or targeting only a single gene, and some advanced treatments have unknown risks. Therefore, these treatments have not been officially approved in China. As a regenerative repair treatment, autologous PRP has been widely used in postoperative repair of fractures in China. There are a large number of clinical studies at home and abroad that confirm that autologous PRP can effectively promote wound healing. As a convenient, painless, low-risk treatment method, rich in a large number of growth factors, the therapeutic effect is remarkable, and autologous PRP treatment is widely accepted by patients.

尽管促创面愈合效果优异，但因为临床上组织创面的多样性，目前市面上没有很好的适应于创面修复的PRP产品，所以国内自体PRP/PRP凝胶在创面治疗中应用并不广泛。目前上市的PRP产品最终制成的多数为PRP液体，无法直接适用于难愈性创面等组织修复的治疗。有些产品结合了凝血酶，使PRP血浆中纤维蛋白原凝聚形成PRP凝胶。但是，自然成型的PRP凝胶结构松散，含水量极高。直接在伤口上使用会出现诸多不良后果：a) 自然成型的PRP凝胶具有极高的含水量，经纱布包扎后，凝胶中的水分会被纱布逐渐吸收，失水后的凝胶会立即内缩，会造成生长因子大量的流失，并造成纱布渗液，增加伤口进一步感染风险。b) 自然成型的PRP凝胶结构松散，易被降解。且凝胶表面湿润光滑，难以持续附着于伤口，极易因患者的移动而导致凝胶移位。c) 从微观结构中发现，自然成型的PRP凝胶的孔径大于白细胞和血小板（＞9μm），因此，无法有效地实现对白细胞和血小板的包载，易在体液的冲刷下快速流失并降解，无法起到持续促修复的作用。因此，PRP在难愈创面治疗使用时仍存在诸多不便和问题。所以急需一款能够改进PRP在难愈伤口应用的产品，以实现PRP在加速伤口组织愈合的良好治疗效果。
Although the wound healing effect is excellent, due to the diversity of clinical tissue wounds, there are no PRP products on the market that are well adapted to wound repair, so domestic autologous PRP/PRP gel is not widely used in wound treatment. Most of the PRP products currently on the market are finally made of PRP liquid, which cannot be directly applied to the treatment of tissue repair such as refractory wounds. Some products combine thrombin to make fibrinogen aggregate in PRP plasma to form PRP gels. However, naturally formed PRP gels have a loose structure and extremely high water content. There are many adverse consequences when used directly on the wound: a) Naturally formed PRP gel has a very high water content, after gauze bandaging, the water in the gel will be gradually absorbed by the gauze, and the gel will immediately shrink after water loss, which will cause a large loss of growth factors and cause gauze exudation, increasing the risk of further infection of the wound. b) Naturally formed PRP gels have a loose structure and are easily degraded. Moreover, the surface of the gel is moist and smooth, making it difficult to continue to adhere to the wound, and it is very easy to cause the gel to shift due to the patient's movement. c) From the microstructure, it is found that the pore size of the naturally formed PRP gel is larger than that of leukocytes and platelets (>9μm), so it cannot effectively realize the encapsulation of leukocytes and platelets, and is easy to be quickly lost and degraded under the washing of body fluids. It cannot play a role in promoting continuous repair. Therefore, there are still many inconveniences and problems in the treatment of refractory wounds. Therefore, there is an urgent need for a product that can improve the application of PRP in difficult-to-heal wounds to achieve a good therapeutic effect of PRP in accelerating wound tissue healing.

鉴于目前市面上多数PRP制备产品针对难愈创面使用的不便捷性，杭州源囊生物科技有限公司研究团队开发出一款可将PRP制备形成浓缩的PRP凝胶补片的成型器产品。该产品作为成型器，通过物理挤压的方式，不改变PRP凝胶的化学结构、生物性能，将松散的血浆凝胶制备成较高强度的血浆凝胶补片。该产品操作简单，制备时间短。挤压成型后的凝胶补片相比于自然成型PRP凝胶，凝胶补片具有更强的力学强度，可以用缝线进行与伤口组织的缝合，可以应伤口的形态随意裁剪；成型后的凝胶补片显著延长了凝胶的降解时间，提升生长因子缓释浓度和时长。目前，本产品已通过国家药品监督管理局（NMPA）认证的检验机构检验且结论为合格，为了进一步评价器械的临床安全性、有效性以及可操作性而申请临床试验。
In view of the inconvenience of most PRP preparation products on the market for the use of difficult-to-heal wounds, the research team of Hangzhou Yuancapsu Biotechnology Co., Ltd. has developed a molder product that can prepare PRP into concentrated PRP gel patches. As a former, the product prepares loose plasma gels into higher-strength plasma gel patches without changing the chemical structure and biological properties of PRP gels through physical extrusion. The product is simple to operate and has a short preparation time. Compared with the naturally formed PRP gel, the gel patch has stronger mechanical strength, and can be sutured with sutures with wound tissue, and can be cut at will according to the shape of the wound. The formed gel patch significantly prolonged the degradation time of the gel and increased the slow-release concentration and duration of growth factors. At present, this product has been inspected by the National Medical Products Administration (NMPA) certified inspection agency and concluded to be qualified, and has applied for clinical trials in order to further evaluate the clinical safety, efficacy and operability of the device.

（二）产品基本信息（包括结构组成、工作原理、作用机理、产品特点等）
(2) Basic product information (including structural composition, working principle, mechanism of action, product characteristics, etc.)

1.产品特点
1.Product features:

本品由成熟医用材料组成，安全性高，生物相容性好。
This product is composed of mature medical materials, with high safety and good biocompatibility.

产品通过物理挤压的方式，将PRP凝胶挤压成补片状，敷贴于慢性创面上，促进创面修复。
The product is physically extrusion, and the PRP gel is squeezed into a patch form and applied to the chronic wound surface to promote wound repair.

2.产品结构组成
2. Product structure composition

本品由外壳、芯杆、胶塞、滤膜和导流片五部分组成，环氧乙烷灭菌，一次性使用。
This product is composed of five parts: shell, core rod, rubber plug, filter membrane and deflector, ethylene oxide sterilization, disposable use.

3.产品工作原理、作用机理
3.The working principle and mechanism of the product

产品通过物理挤压的方式，将PRP凝胶中水分滤出，挤压成补片状，增强了PRP凝胶的力学强度，血小板和生长因子浓度。将凝胶补片敷贴于慢性创面上，可促进创面修复。
The product filters out the water in the PRP gel through physical extrusion and extrudes it into a patch shape, which enhances the mechanical strength, platelet and growth factor concentration of the PRP gel. Gel patches applied to chronic wounds can promote wound repair.

（三）适用范围以及相关信息
(3) Scope of application and relevant information

1.适应症
1.Indications:

产品由医生在医疗机构使用，用于将富血小板血浆及凝血酶加工形成凝胶补片，并将其立即用于患者组织修复。
The product is used by doctors in medical institutions to process platelet-rich plasma and thrombin into gel patches, which are immediately used for tissue repair in patients.

2.禁忌症
2.Contraindications

对一次性使用凝胶补片成型器中的橡胶等成分过敏，严禁使用本产品。
If you are allergic to rubber and other ingredients in the single-use gel patch former, it is strictly forbidden to use this product.

3.注意事项
3.Notes:

在使用过程中发现包装有破损、开裂等现象以及超过有效期时，禁止使用。
If the packaging is found to be damaged or cracked during use or if it exceeds the expiration date, it is prohibited to use it.

产品为一次性使用，严禁重复使用。
The product is for one-time use and reuse is strictly prohibited.

本产品需由专业医护人员经相关培训合格后，严格按照说明书进行操作使用。
This product needs to be operated and used by professional medical personnel in strict accordance with the instructions after relevant training and qualification.

本产品使用后请按照医疗垃圾进行处理。
After use, please dispose of this product as medical waste.

产品使用过程中需自备1mL、10mL等不同规格的产品配液器和相应的配液针；
During the use of the product, you need to bring your own product dispensers of different specifications such as 1mL and 10mL and corresponding dispensing needles;

产品使用过程中需自备药用凝血酶；
During the use of the product, it is necessary to prepare its own pharmaceutical thrombin;

产品使用过程中需自备一次性使用医用三通阀；
During the use of the product, it is necessary to prepare its own disposable medical three-way valve;

产品使用过程中需自备适配的支架。
During the use of the product, you need to bring your own adaptive bracket.

四、试验目的
4. Purpose of the experiment

研究一次性使用凝胶补片成型器临床操作使用的安全性和有效性。
To investigate the safety and efficacy of the single-use gel patch former for clinical operational use.

五、试验设计
5. Experimental design

（一）总体设计以及确定依据
(1) Overall design and determination basis

本次临床试验采用多中心、随机、平行对照、优效性试验设计，选择医疗器械临床试验机构备案管理信息系统中的临床试验机构。所有受试者签署知情同意书后，经筛选合格，采集其基本信息，随机入组试验组或对照组，进行临床试验，观察产品的安全性和有效性。
This clinical trial adopts a multicenter, randomized, parallel-controlled, and superiority test design, and selects clinical trial institutions in the medical device clinical trial institution filing management information system. After all subjects sign the informed consent form, their basic information is collected and randomly enrolled in the experimental group or control group to conduct clinical trials to observe the safety and efficacy of the product.

前瞻性：避免回顾性试验产生的选择性偏倚和回忆偏倚，研究结果更具科学性；
Prospective: avoid selectivity bias and recall bias caused by retrospective trials, and the results are more scientific;

多中心：采用多中心临床试验，在相同的时间段可获得比单个中心更多的病例，因此可缩短临床试验时间；由于多中心试验是由不同医院不同研究者完成，结论更具有广泛的代表性。
Multicenter: Multicenter clinical trials can shorten the clinical trial time by using multicenter clinical trials to obtain more cases than a single center in the same time period; Since the multicenter trial was completed by different researchers in different hospitals, the conclusions were more broadly representative.

随机：研究者根据随机原则将受试者纳入试验组或对照组，保证了除处理因素外，其他可能产生的混杂效应在各组中尽可能保持一致，从而保持各组的均衡性。
Randomization: The investigator enrolled the subjects in the experimental or control group according to the principle of randomization, ensuring that the possible confounding effects were as consistent as possible among the groups except for the treatment factors, so as to maintain the balance of the groups.

平行对照：本次临床试验采用治疗慢性创面常用的PRP凝胶作为对照治疗方法，该方法已形成专家共识，与该方法进行比较可以得出科学的结论。
Parallel control: This clinical trial uses PRP gel, which is commonly used for the treatment of chronic wounds, as a control treatment, which has formed an expert consensus and can be compared with this method to draw scientific conclusions.

先签知情后筛选入组：保障受试者知情权，也保证受试者自主选择权，维护受试者权益。
Sign first and inform before screening and enrollment: Protect the subject's right to know, and also ensure the subject's right to choose independently, and safeguard the rights and interests of the subject.

（二）受试者选择
(2) Subject selection

1.入选标准
1. Selection criteria

18周岁-75周岁；
18-75 years old;

需进行清创修复的慢性创面患者；
Patients with chronic wounds requiring debridement repair;

伤口持续时间＞4周；
Wound duration> 4 weeks;

自愿参加本研究，并签署知情同意书；
Volunteer to participate in this study and sign the informed consent form;

2.排除标准
2. Exclusion criteria

重度血小板减少症、败血症的患者；
Patients with severe thrombocytopenia and sepsis;

对橡胶成分过敏患者；
Patients who are allergic to rubber ingredients;

1月内注射过糖皮质激素、或2周内进行全身皮质激素治疗的患者；
Patients who have been injected with glucocorticoids within 1 month or systemic corticosteroid therapy within 2 weeks;

恶性肿瘤患者；
Patients with malignant tumors;

血红蛋白＜100g/L，血小板计数＜100×10⁹/L；
Hemoglobin < 100g/L, platelet count < 100×10⁹/L ；

精神疾病者、认知损伤者、危重患者、未成年人、孕妇；
Mental illness, cognitive impairment, critically ill patients, minors, and pregnant women;

3个月内参加过或正在参加药物临床试验，或 30天内参加过或正在参加其他医疗器械临床试验者；
Those who have participated in or are participating in drug clinical trials within 3 months, or have participated in or are participating in other medical device clinical trials within 30 days;

研究者认为不宜参与研究的其他情况。
Other conditions that the investigator deems unsuitable for participation in the study.

3.受试者退出标准和程序
3. Subject withdrawal criteria and procedures

受试者自行退出
Subjects withdraw on their own

无论何种原因，受试者不愿意或不可能继续进行临床试验，向研究者提出退出临床试验的要求而终止临床试验者；
Regardless of the reason, the subject is unwilling or unable to continue the clinical trial, and the clinical trial is terminated by requesting the investigator to withdraw from the clinical trial;

受试者虽未明确提出退出临床试验，但不再接受治疗及检查而失访者。
Although the subjects did not explicitly propose to withdraw from the clinical trial, they no longer received treatment and examination and were lost to follow-up.

研究者决定退出
The researcher decided to withdraw

受试者出现过敏反应或严重不良事件（Serious Adverse Event，SAE），且无法完成后续的试验，根据研究者判断应终止临床试验；
Subjects with allergic reactions or serious adverse events (SAEs) and unable to complete subsequent trials, the clinical trial should be terminated according to the investigator's judgment;

临床试验过程中，受试者发生其他并发症，不宜继续接受临床试验；
During the clinical trial, the subject has other complications and is not suitable to continue to undergo the clinical trial;

受试者不符合试验的入选标准、符合排除标准而被错误入选，且未使用试验器械；
Subjects who do not meet the inclusion criteria of the trial, are wrongly selected due to meeting the exclusion criteria, and do not use the test device;

临床试验过程中该受试者出现严重的方案偏离，如试验过程中使用非本方案中规定器械，或中途用非规定范围内联合用药，已无法对其临床试验结果进行有效评价；
During the clinical trial, the subject has serious deviations from the protocol, such as the use of devices not specified in this protocol during the trial, or the use of combined drugs within the scope of non-specified drugs in the middle of the trial, which can no longer effectively evaluate the clinical trial results;

受试者依从性差。
Poor subject compliance.

受试者试验终止后，研究者应该从保障受试者权益的角度，继续为受试者提供适当的治疗，并详细告知受试者在其试验期间所接受的治疗及相关处理。受试者的相关数据依旧可以用于评价产品的安全性。研究者应将受试者试验终止的情况及时反馈给申办方。
After the termination of the subject's trial, the investigator should continue to provide appropriate treatment to the subject from the perspective of protecting the rights and interests of the subject, and inform the subject in detail of the treatment and related treatment received during the trial. Data from subjects can still be used to evaluate the safety of the product. The investigator should promptly feedback the termination of the subject's trial to the sponsor.

（三）评价方法
(3) Evaluation methods

1.有效性评价
1. Effectiveness evaluation

主要评价指标
Main evaluation indicators

主要评价指标为血小板浓度合格率。
The main evaluation index was the qualified rate of platelet concentration.

评价方法：测试PRP和通过产品制备的凝胶补片中的血小板浓度。
Evaluation methods: Platelet concentrations in PRP and gel patches prepared by the product were tested.

取抗凝外周血（约20mL，平均分为富血小板血浆（PRP）组和凝胶补片（补片）组），PRP组经150×g离心10分钟后获得上层血浆和血小板，将10mL含血小板血浆转移至新的离心管中，再次800×g离心5分钟，弃去约3/4的上清，下层混匀获得富血小板血浆，测量血小板浓度记为。
Anticoagulant peripheral blood (about 20mL, evenly divided into platelet-rich plasma (PRP) group and gel patch (patch) group) was collected, and the PRP group was 150 ×g centrifugation 1 0 min to obtain the upper layer of plasma and platelets, transfer 10 mL of platelet-containing plasma to a new centrifuge tube, and centrifuge again at 800×g For 5 minutes, discard about 3/4 of the supernatant, mix the lower layer well to obtain platelet-rich plasma, and measure the platelet concentration as .

补片组经150×g离心10分钟后获得上层血浆和血小板，测量血小板血浆体积和血小板浓度。根据产品说明书，将血小板血浆和1/10体积的凝血酶在一次性凝胶补片成型器中混匀，然后挤压加工成凝胶补片。保留滤出液体，测得滤出液体积和血小板浓度。
The upper layer of plasma and platelets were obtained after centrifugation of 150×g for 10 minutes, and the platelet plasma volume and platelet concentration were measured. According to the product manual, platelet plasma and 1/10 volume of thrombin are mixed in a disposable gel patch former and then extruded into a gel patch. The leachate liquid was retained, and the volume of the leachate fluid and platelet concentration were measured.

测量并根据公式计算各组的血小板浓度。
Platelet concentrations in each group were measured and calculated according to the formula.

记录时间：PRP凝胶补片制备完成后3小时内。
Recording time: within 3 hours after the preparation of PRP gel patches.

分析方法：根据评价方法制备样品并测量，根据下列公式计算凝胶补片中血小板浓度。
Analysis method: Prepare the sample according to the evaluation method and measure it, and calculate the platelet concentration in the gel patch according to the following formula.

根据患者V1访视的血常规血小板浓度，根据下列公式计算对照组和试验组血小板的富集倍数N：
According to the blood routine platelet concentration of the patient V1 visit, the enrichment factor N of platelets in the control group and the test group was calculated according to the following formula:

对照组： 试验组：
Control group: Experimental group:

若富集倍数处于2-8倍区间内，则认为合格。
If the enrichment multiple is in the range of 2-8 times, it is considered qualified.

计算两组血小板浓度的合格率并进行优效性检验。
The pass rate of platelet concentration in the two groups was calculated and the superiority test was performed.

次要评价指标
Secondary evaluation indicators

次要评价指标1：术后3天创面细菌情况。
Secondary evaluation indicator 1: Wound bacteria 3 days after surgery.

评价方法：术中清创术结束和术后3天，由研究者取对照组和试验组创面部位分泌物进行细菌培养检查。
Evaluation methods: At the end of intraoperative debridement and 3 days after surgery, the investigator took the secretions from the wound site of the control group and the experimental group for bacterial culture examination.

记录时间：术中（清创术结束）和术后3天。
Recording time: intraoperative (end of debridement) and 3 days postoperatively.

分析方法：根据下表，对两组创面细菌情况进行评分，并在两组间对评分结果进行组间差异分析。
Analysis methods: According to the table below, the bacterial situation of the wound in the two groups was scored, and the difference analysis between the scores was performed between the two groups.

次要评价指标2：生长因子浓度。
Secondary evaluation index 2: growth factor concentration.

评价方法：取约20mL抗凝外周血，平均分为PRP组和补片组。PRP组经150×g离心10分钟后获得上层血浆和血小板，将含血小板血浆转移至新的离心管中，再次800×g离心5分钟，弃去3/4的上清，下层混匀获得富血小板血浆，加入1/10体积的凝血酶成胶后放入50mL离心管中，加入4倍体积的生理盐水37℃浸提1小时。
Evaluation methods: Approximately 20mL of anticoagulant peripheral blood was collected, and it was evenly divided into PRP group and patch group. The upper layer of plasma and platelets were obtained after centrifugation at 150×g for 10 minutes, and the platelet-containing plasma was transferred to a new centrifuge tube againCentrifuge 800×g for 5 minutes, discard 3/4 of the supernatant, mix the lower layer well to obtain platelet-rich plasma, add 1/10 volume of thrombin to form a gel and put in 50 In a mL centrifuge tube, add 4 times the volume of normal saline at 37°C for 1 hour.

补片组经150×g离心10分钟后获得含血小板血浆，根据产品说明书，将含血小板血浆和1/10体积的凝血酶在一次性凝胶补片成型器中混匀，然后挤压加工成凝胶补片，将补片放入50mL离心管中，加入4倍体积的生理盐水37℃浸提1小时。浸提结束后，取出凝胶和凝胶补片，用ELISA试剂盒检测PDGF-BB、TGF-β1和IL-1β三个因子的浓度。
According to the product manual, platelet-containing plasma and 1/10 volume of thrombin were mixed in a disposable gel patch former, and then extruded into gel patches.× Place the patch in a 50mL centrifuge tube and add 4 times the volume of normal saline to 37 °C for 1 h. After extraction, the gel and gel patch were removed and PDGF-BB, TGF-β 1 and IL-1β were detected with the ELISA kit Concentration of three factors.

记录时间：PRP凝胶和凝胶补片制备完成后12小时内。
Recording time: within 12 hours after the preparation of PRP gel and gel patch is completed.

分析方法：根据评价方法检测PRP凝胶和凝胶补片释放的生长因子浓度，并进行组间差异分析。
Analysis methods: The concentration of growth factors released by PRP gel and gel patch was detected according to the evaluation method, and the difference analysis between groups was carried out.

次要评价指标3：极限拉力强度。
Secondary evaluation index 3: ultimate tensile strength.

评价方法：取血小板浓度检测试验的剩余富血小板血浆（PRP组）和凝胶补片（补片组）进行拉力强度检测。
Evaluation methods: The remaining platelet-rich plasma (PRP group) and gel patch (patch group) were taken for tensile strength testing.

PRP组将1.8mL富血小板血浆和1/10体积的的凝血酶加入φ35mm的圆饼型培养皿中成胶。
In the PRP group, 1.8mL of platelet-rich plasma and 1/10 volume of thrombin were added to φ35 mm round cake dish to form a gel.

将PRP组凝胶和补片组凝胶补片用手持式拉力计检测凝胶能承受的最大拉力。
The maximum tensile force that the gel can withstand is tested with a handheld tensile meter.

记录时间：PRP凝胶和凝胶补片制备完成后3小时内。
Recording time: within 3 hours after the preparation of PRP gel and gel patch is completed.

分析方法：根据评价方法记录PRP凝胶和凝胶补片的最大极限拉力，并进行组间差异分析，以验证产品增强凝胶拉力的有效性。
Analysis methods: The maximum ultimate tensile force of PRP gel and gel patch was recorded according to the evaluation method, and the difference analysis between groups was performed to verify the effectiveness of the product in enhancing the gel tensile force.

次要评价指标4：术后伤口情况
Secondary evaluation criterion 4: postoperative wound condition

评价方法：术后3天，研究者按照《伤口评估表》对受试者伤口进行打分，以评估伤口感染情况。《伤口评估表》如下：
Evaluation method: Three days after surgery, the investigator scored the wound of the subjects according to the "Wound Assessment Form" to evaluate the wound infection. The Wound Assessment Form is as follows:

参考文献：
References:

Armstrong DG., et al. Diabetic Foot Ulcers: A Review. JAMA. 2023. Jul; 3;330(1):62-75.
Armstrong DG., et al. Diabetic Foot Ulcers: A Review. JAMA. 2023. Jul; 3; 330(1):62-75.

记录时间：术后3天。
Recording time: 3 days postoperatively.

分析方法：根据评价方法检测对照组和试验组术后3天创面情况进行打分，并在两组间进行组间差异分析。
Analysis method: The wound of the control group and the test group was scored according to the evaluation method at 3 days after surgery, and the difference analysis between the two groups was carried out.

次要评价指标5：产品使用性能
Secondary evaluation indicator 5: product use performance

评价方法：术后由手术研究者对试验器械进行使用性能评价，评价内容如下：
Evaluation method: The performance of the test instrument was evaluated by the surgical investigator after surgery, and the evaluation content was as follows:

产品性能、操作过程、制备性能三个维度中，每个维度至少有1项评价为“是”，并且上述12项评价内容至少9项评价为“是”，使用性能评价为“满意”；否则，使用性能评价为“不满意”。
Among the three dimensions of product performance, operation process, and preparation performance, at least one evaluation in each dimension is "yes", and at least 9 of the above 12 evaluation contents are rated as "yes", and the performance evaluation is "satisfactory". Otherwise, the performance of the use is rated as "unsatisfactory".

记录时间：手术完成当天。
Recording time: The day the surgery is completed.

分析方法：根据评价方法及下列公式，统计试验器械使用性能满意度。
Analysis method: According to the evaluation method and the following formula, the satisfaction of the performance of the test instrument is counted.

次要评价指标6：血小板浓度
Secondary evaluation indicator 6: platelet concentration

评价方法：根据主要评价指标中测量计算结果获得PRP组和补片组血小板浓度。对
Evaluation methods: The platelet concentrations of P RP group and patch group were obtained according to the measurement and calculation results in the main evaluation indicators. Right

记录时间：PRP凝胶补片制备完成后3小时内。
Recording time: within 3 hours after the preparation of PRP gel patches.

分析方法：对PRP组和补片组的血小板浓度进行组间差异分析。
Analysis methods: The platelet concentrations of PRP group and patch group were analyzed between groups.

2.安全性评价
2. Safety evaluation

安全性评价指标1：实验室检查异常情况
Safety evaluation index 1: Abnormal laboratory examination

评价方法：术后3天复查血常规、肝功能、肾功能，记录血常规中红细胞计数（RBC）、白细胞计数（WBC）、中性粒细胞比率（NEUT%）、血红蛋白浓度（HGB）、血小板计数（PLT）检查结果；记录肝功能中谷草转氨酶（AST）、谷丙转氨酶（ALT）检查结果；记录肾功能中肌酐（CRE）、尿素氮（BUN）或尿素（UREA）检查结果。记录血液C反应蛋白结果。如果检查结果正常或异常但无临床意义，则判定结果正常，如果检查结果异常有临床意义，则按照异常结果处理。
Evaluation methods: Blood routine, liver function, and kidney function were reviewed 3 days after surgery, and red blood cell count (RBC), white blood cell count (WBC), neutrophil ratio (NEUT%), and hemoglobin concentration () were recorded in blood routine HGB), platelet count (PLT) test results; The results of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in liver function were recorded. The results of creatinine (CRE), urea nitrogen (BUN) or urea (UREA) tests in renal function were recorded. Record blood C-reactive protein results. If the test results are normal or abnormal but not clinically significant, the results are judged to be normal, and if the test results are abnormal and clinically significant, they are treated as abnormal results.

记录时间：术后3天。
Recording time: 3 days postoperatively.

分析方法：根据评价方法及下列公式计算实验室检查异常情况。
Analysis method: Calculate laboratory abnormalities according to the evaluation method and the following formula.

安全性评价指标2：生命体征检查情况
Safety evaluation index 2: vital sign examination

评价方法：术后3天复查基本生命体征，记录体温、脉搏、呼吸、血压。
Evaluation methods: Basic vital signs were reviewed 3 days after surgery, and body temperature, pulse, respiration, and blood pressure were recorded.

记录时间：术后3天。
Recording time: 3 days postoperatively.

分析方法：根据评价方法，记录试验组和对照组术后3天的生命体征，进行组间差异性分析。
Analysis method: According to the evaluation method, the vital signs of the experimental group and the control group were recorded 3 days after surgery, and the difference between groups was analyzed.

安全性评价指标3：不良事件和严重不良事件发生情况
Safety evaluation index 3: occurrence of adverse events and serious adverse events

评价方法：试验过程中出现的任何不利的医学事件，无论是否与器械有关，均为不良事件。如果临床试验过程中发生导致死亡或者健康状况严重恶化的事件，则判定为严重不良事件。所有不良事件和严重不良事件均需判定是否与受试器械有关。不良事件和严重不良事件与受试器械的关系，分为“肯定有关”、“很可能有关”、“可能有关”、“可能无关”、“无关”，通过不良事件、严重不良事件发生率和与器械相关的不良事件、严重不良事件反映受试器械的安全性。
Evaluation methodology: Any adverse medical event during the trial, whether or not device-related, is an adverse event. Serious adverse events are determined if they occur during the course of a clinical trial that result in death or serious deterioration of health. All adverse events and serious adverse events should be determined to be related to the test device. The relationship between adverse events and serious adverse events and the test device is divided into "definitely related", "likely related", "possibly related", "possibly unrelated", "not related", and divided into adverse events, serious adverse events and device-related adverse events, Serious adverse events reflect the safety of the test device.

试验器械预期的不良事件包括：器械缺陷、伤口不适、创面感染等。
Expected adverse events of the test device include: device defects, wound discomfort, wound infection, etc.

器械缺陷情况：指术中是否存在器械包装破损、器械破损等功能故障的事件发生。
Device defects: refers to whether there are functional failures such as broken device packaging and equipment damage during surgery.

伤口不适情况：指术后是存在伤口剧烈疼痛、麻木、瘙痒的事件发生。
Wound discomfort: refers to the occurrence of severe pain, numbness, and itching in the wound after surgery.

创面感染情况：指术后是否发生创面感染事件发生。
Wound infection: refers to whether wound infection occurs after surgery.

注：与临床诊断和既往基础疾病相关的病情（以基线检查或既往病史为准），如果严重程度和治疗方法没有改变，可不作为不良事件报告。
Note: Conditions related to clinical diagnosis and previous underlying disease (based on baseline examination or past medical history) may not be reported as adverse events if the severity and treatment do not change.

记录时间：从受试者确定入组到术后3天出组。
Recording time: From the time the subject is confirmed to enroll to the group 3 days after surgery.

分析方法：根据评价方法记录试验过程中发生的不良事件和严重不良事件，根据下列公式计算不良事件及严重不良事件发生率，并进行组间差异性分析。
Analysis methods: Adverse events and serious adverse events that occurred during the trial were recorded according to the evaluation method, and the incidence of adverse events and serious adverse events was calculated according to the following formula, and the difference analysis between groups was carried out.

（四）试验医疗器械和对照诊疗方法
(4) Experimental medical devices and control diagnosis and treatment methods

1.试验组
1. Test group

采集外周血液，清创术后，采用经一次性使用凝胶补片成型器制备的PRP凝胶补片敷于创面。剩余血液用于PRP凝胶和凝胶补片的性能检测。
Peripheral blood was collected, and after debridement, PRP gel patches prepared by a disposable gel patch former were applied to the wound surface. The remaining blood was used for performance detection of P RP gels and gel patches.

2.对照组
2. Control group

采集外周血液，清创术后，采用PRP凝胶敷于创面。剩余血液用于PRP凝胶和凝胶补片的性能检测。
Peripheral blood was collected, and after debridement, PRP gel was applied to the wound surface. The remaining blood was used for performance detection of P RP gels and gel patches.

（五）试验流程
(5) Test process

1.试验流程表
1. Test flow chart

表3试验流程表
Table 3 Test flow table

2.试验实施（方法、内容、步骤等）
2. Experimental implementation (methods, contents, steps, etc.).

病例入组
Case enrollment

签署知情同意书（签名及日期），记录受试者基本信息，包括出生日期、性别、身高、体重、临床诊断和既往病史、过敏史等。记录入组前需要进行临床相关项目的检查结果。根据入选标准和排除标准选择合适的受试者。
Sign the informed consent form (signature and date), and record the subject's basic information, including date of birth, gender, height, weight, clinical diagnosis and past medical history, allergy history, etc. Record the results of the examination that need to be performed before enrollment. Appropriate subjects are selected according to the inclusion and exclusion criteria.

检查/检测项目
Inspection/Inspection Items

访视1：筛选期检查
Visit 1: Screening period examination

术前肝功能检查：谷丙转氨酶（ALT）、谷草转氨酶（AST）。
Preoperative liver function tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST).

术前肾功能检查：肌酐（CRE）、尿素氮（BUN）或尿素（UREA）。
Preoperative renal function tests: creatinine (CRE), urea nitrogen (BUN), or urea (UREA).

术前血常规检查：红细胞计数（RBC）、白细胞计数（WBC）、中性粒细胞比率（NEUT%）、淋巴细胞比率（LTMPH%）、血红蛋白浓度（HGB）、血小板计数（PLT）。
Preoperative blood routine examination: red blood cell count (RBC), white blood cell count (WBC), neutrophil ratio (NEUT%), lymphocyte ratio (LTMPH%), hemoglobin concentration (HGB). ), platelet count (PLT).

术前C反应蛋白检查。
Preoperative C-reactive protein test.

生命体征（体温、脉搏、呼吸、血压）。
Vital signs (temperature, pulse, respiration, blood pressure).

访视2：慢性溃疡修复术
Visit 2: Chronic ulcer repair

术前外周血抽取。
Preoperative peripheral blood draw.

清创术后创面分泌物细菌培养。
Bacterial culture of wound secretions after debridement.

术后产品使用性能评价。
Evaluation of product use performance after surgery.

访视3（术后3天内）：
Visit 3 (within 3 days after surgery):

创面分泌物细菌培养。
Bacterial culture of wound secretions.

血常规检查：红细胞计数（RBC）、白细胞计数（WBC）、中性粒细胞比率（NEUT%）、淋巴细胞比率（LTMPH%）、血红蛋白浓度（HGB）、血小板计数（PLT）。
Blood routine tests: red blood cell count (RBC), white blood cell count (WBC), neutrophil ratio (NEUT%), lymphocyte ratio (LTMPH%), hemoglobin concentration (HGB). ), platelet count (PLT).

肝功能检查：谷丙转氨酶（ALT）、谷草转氨酶（AST）。
Liver function tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST).

肾功能检查：肌酐（CRE）、尿素氮（BUN）或尿素（UREA）。
Renal function tests: creatinine (CRE), urea nitrogen (BUN), or urea (UREA).

术后C反应蛋白检查。
Postoperative C-reactive protein examination.

创面情况评估。
Wound assessment.

生命体征（体温、脉搏、呼吸、血压）。
Vital signs (temperature, pulse, respiration, blood pressure).

确认组别
Confirm the group

本试验根据随机原则确认受试者试验组别。
This trial identifies the trial group of subjects according to the principle of randomization.

受试者签署知情同意书后先给筛选号，筛选合格后给予受试者编号。
After the subjects sign the informed consent form, they will be given a screening number first, and the subject number will be given after passing the screening.

筛选号为S+2位数的试验中心编号+2位数的流水号组成，按照签署知情同意书时间给予筛选号，流水号不足2位时往前增加0补足2位。
The screening number is composed of S+2-digit trial center number + 2-digit serial number, and the screening number is given according to the time of signing the informed consent form, and the serial number is less than 2When the position is increased, 0 is added forward to make up for 2 digits.

用统计软件编程，按中心分层，给定区组长度，按1:1比例将受试者分为试验组和对照组，产生至少38例受试者的随机分组安排，并制定相应的随机数字表。
Programmed with statistical software, stratified by center, given block length, subjects were divided into experimental and control groups in a 1:1 ratio, resulting in a randomization arrangement of at least 38 subjects, and a corresponding random number table was developed.

受试者编号为中心编号和流水号组成的四位数，前2位为试验中心编号，后2位为流水号，流水号不足2位时往前增加0补足2位。受试者入选后，研究者根据随机信封确认受试者组别，并采取相应组别的器械给受试者进行治疗。
The subject number is a four-digit number composed of the center number and the serial number, the first 2 digits are the test center number, the last 2 digits are the serial number, and if the serial number is less than 2 digits, 0 is added forward to make up for 2 digits. After the subjects are selected, the investigator confirms the subject group according to the random envelope and takes the corresponding group of devices for treatment.

试验操作步骤
Experimental procedure

手术当天术前，静脉抽取患者大概50-60mL外周血，尽量可采集到60mL。
On the day of surgery, about 50-6 0mL of peripheral blood is drawn from the patient's vein, and 6 0mL can be collected as much as possible.

取其中约20mL外周血，对照组经150×g离心后获得上层血浆和血小板，转移至新的离心管中，再次800×g离心，弃去约3/4的上清，下层混匀获得富血小板血浆。试验组进行相同的第一步离心操作，获得含血小板血浆备用。制备完成后于1-10℃保存，根据需要送至手术室。剩余血液用于检测血小板浓度、拉力和生长因子浓度。
About 20mL of peripheral blood was taken, and the control group was centrifuged with 150×g of upper plasma and platelets, which were transferred to a new centrifuge tube and another 800×gCentrifugation, discard about 3/4 of the supernatant, and mix the lower layer to obtain platelet-rich plasma. The test group performed the same first step of centrifugation to obtain platelet-containing plasma for backup. After preparation, store at 1-10°C and send to the operating room as needed. The remaining blood is used to measure platelet concentration, tension, and growth factor concentration.

按照常规手术要求对创面部位进行消毒，充分切除坏死组织，彻底清创，直至健康出血的软组织完全暴露。根据文献报道，我们设计了针对清创治疗的评估表（表4《清创评估表》），研究者根据表进行打分，当三个维度分数均≥4分，且总分≥12分时，可认为清创完全，取创面处分泌送进行细菌培养检测。
The wound site is disinfected according to the requirements of routine surgery, the necrotic tissue is fully removed, and the debridement is thorough until the soft tissue with healthy bleeding is completely exposed. According to the literature report, we designed an evaluation form for debridement treatment (Table 4 "Debridement Evaluation Form"), according to which the researcher scored according to the table, and when the scores of all three dimensions ≥ 4 points, and the total score ≥ 12 points, the debridement can be considered complete, and the secretion from the wound surface can be sent for bacterial culture testing.

参考文献：
References:

Schultz, G., et al. Wound Bed Preparation: A Systematic Approach to Wound Management. Wounds International, 2003. Mar;11 Suppl 1:S1-28.
Schultz, G., et al. Wound Bed Preparation: A Systematic Approach to Wound Management. Wounds International, 2003. Mar; 11 Suppl 1:S1-28.

Falanga, V. Wound Healing and Its Impairment in the Diabetic Foot. The Lancet, 2005. Nov 12;366(9498):1736-43.
Falanga, V. Wound Healing and Its Impairment in the Diabetic Foot. The Lancet, 2005. Nov 12; 366(9498):1736-43.

Armstrong, D.G., et al. Debridement: The Key to Wound Healing. Podiatry Management, 2000. Dec;6(4):627-60.
Armstrong, D.G., et al. Debridement: The Key to Wound Healing. Podiatry Management, 2000. Dec; 6(4):627-60.

Wolcott, R.D., et al. "Biofilms and Chronic Wound Inflammation." Journal of Wound Care, 2008. Aug;17(8):333-41.
Wolcott, R.D., et al. "Biofilms and Chronic Wound Inflammation." Journal of Wound Care, 2008. Aug; 17(8):333-41.

对照组在富血小板血浆中以1:10的体积加入凝血酶，静置3分钟后形成凝胶。其中对照组用无菌镊子轻轻夹取凝胶敷于创面处。
The control group added thrombin in platelet-rich plasma at a volume of 1:10 and left for 3 minutes to form a gel. The control group used sterile forceps to gently pick up the gel and apply it to the wound.

试验组按器械操作说明书将血浆和凝血酶注入成型器中，挤压形成凝胶补片，用无菌镊子轻轻夹取凝胶敷于创面处。
The experimental group injected plasma and thrombin into the molding device according to the instrument operation manual, squeezed to form a gel patch, and gently picked up the gel with sterile forceps and applied it to the wound.

若手术中有特殊需要，可在无菌条件下对凝胶补片进行适当裁剪，并根据需要将补片与软组织进行缝合固定。
If there is a special need for surgery, the gel patch can be cut appropriately under sterile conditions, and the patch can be sutured and fixed with the soft tissue as needed.

按照常规手术要求缝合创面并用敷料覆盖包扎。
The wound is sutured and covered with a dressing according to the requirements of the routine operation.

3.用械规范
3. Specifications for the use of equipment

申办者应当参照国家药品监督管理局有关医疗器械说明书和标签管理的规定，对试验用医疗器械作适当的标识，并标注“医疗器械临床试验专用”。
The sponsor shall refer to the regulations of the State Medical Products Administration on the management of medical device instructions and labels, and make appropriate labels for experimental medical devices, and mark them as "special for clinical trials of medical devices".

试验用医疗器械的记录包括生产日期、产品型号、批号/序列号等与生产有关的记录，运输、储存、交付各临床试验机构使用的记录，以及试验后回收与处置日期等方面的信息。
Records of experimental medical devices include production-related records such as production date, product model, batch number/serial number, transportation, storage, and delivery to clinical trial institutions, and post-trial recall and disposal dates.

试验用医疗器械的使用由临床试验机构和研究者负责，研究者应当保证所有试验用医疗器械仅用于该临床试验的受试者，在试验期间按照要求储存和保管试验用医疗器械，在临床试验后按照国家有关规定和与申办者的协议对试验用医疗器械进行处理。上述过程需由专人负责并记录。研究者不得把试验用医疗器械转交任何非临床试验参加者。
The use of experimental medical devices is the responsibility of the clinical trial institution and the investigator, and the investigator shall ensure that all experimental medical devices are only used for subjects in the clinical trial, store and keep the experimental medical devices as required during the trial, and dispose of the experimental medical devices in accordance with relevant national regulations and agreements with the sponsor after the clinical trial. The above process needs to be handled and recorded by a special person. Investigators are not allowed to transfer the investigational medical device to any non-clinical trial participant.

4.合并治疗（如用药）规范
4. Combined treatment (such as medication) specifications

合并用药包括任何可能影响本试验结果的用药，如抗生素、止疼药等，从受试者签署知情同意书后开始记录，持续到受试者出组。术中常规辅助用药无需记录，如麻醉药、生理盐水、葡萄糖、维生素类、电解质类等药物。根据本试验特点，收集的合并用药为与创面疾病相关以及其他重要的伴随用药治疗。收集合并用药相关信息应该（至少）包括药物的通用名、单次剂量、频次、用途、开始和停止或持续状态。
Concomitant medications include any medications that may affect the results of this trial, such as antibiotics, analgesics, etc., which are recorded from the time the subject signs the informed consent form and continues until the subject leaves the group. Routine adjuvant medications during surgery do not need to be recorded, such as anesthetics, saline, glucose, vitamins, electrolytes and other drugs. According to the characteristics of this trial, the collected concomitant drugs were related to wound disease and other important concomitant drug treatments. Collecting information about concomitant medications should (at least) include the generic name of the drug, single dose, frequency, use, start and stop, or duration status.

（六）偏倚控制措施
(6) Bias control measures

临床开始前，申办者对参与研究的研究者进行相关培训，确保研究者充分了解研究流程，熟练操作试验器械。
Before the start of clinical trials, the sponsor conducts relevant training for the researchers participating in the study to ensure that the researchers fully understand the research process and are proficient in operating the test equipment.

临床试验过程中，研究者必须严格按照临床方案中的操作方法及规程进行操作，临床试验监查员应做好质量控制与监查工作，确保研究者严格按照研究方案进行操作、实施。以上措施贯彻在整个研究的实施阶段，以减少过失或操作误差。
During the clinical trial, the investigator must strictly follow the operation methods and procedures in the clinical protocol, and the clinical trial monitor should do a good job in quality control and monitoring to ensure that the researcher strictly follows the operation and implementation of the research plan. These measures are implemented throughout the implementation phase of the study to reduce errors or operational errors.

采用严格的分层区组随机化分配试验组别，避免选择性偏倚；试验开始后，当受试者满足试验的入选标准时，由研究者根据随机原则确认受试者组别。
Strict stratified block randomization was used to allocate experimental groups to avoid selective bias. After the start of the trial, when the subjects meet the inclusion criteria of the trial, the investigator will confirm the subject group according to the random principle.

严格根据试验方案的入选和排除标准对受试者进行筛选，减少选择性偏倚。
Subjects were screened strictly according to the inclusion and exclusion criteria of the trial protocol to reduce selective bias.

参与本临床试验的研究者均具有相关工作经验，保证了操作的熟练性和规范性。
The researchers participating in this clinical trial all have relevant work experience, which ensures the proficiency and standardization of the operation.

临床研究完成时，做好数据保管与整理工作。
When the clinical study is completed, do a good job of data storage and collation.

六、统计学考虑
6. Statistical considerations

（一）样本量估算
(1) Sample size estimation

1.总样本量
1. Total sample size

本试验主要评价指标为经一次性使用凝胶补片成型器制备的血小板凝胶补片中血小板浓度优效于相同条件下制备的富血小板血浆中血小板浓度。因此本试验根据公式：
The main evaluation indicators of this trial were that the concentration of platelets in platelet gel patches prepared by a disposable gel patch former was superior to that in platelet-rich plasma prepared under the same conditions. Therefore, this trial is based on the formula:

其中α=0.05，β=0.2。PC和PT为对照组和试验组血小板浓度符合设定阈值的成功率， 为PC和PT的差值绝对值，∆为优效界值，取正值。
where α=0.05, β=0.2. PC and PT are the success rates of platelet concentrations in the control group and the test group that meet the set threshold, which is the absolute value of the difference between PC and PT. ∆ is the threshold value, and the positive value is taken.

根据临床实际情况，此处PC为15%，PT为65%，∆=0.1。代入公式得，N=36。
According to the clinical situation, P C is 15%, PT is 65%, ∆ = 0.1. The substitution formula yields , N=36.

按照统计学要求，此次临床试验共选合格病例36例才具有统计学意义。按照5%的脱落率计算，最终需要入选病例38例。
According to statistical requirements, a total of 36 qualified cases were selected for this clinical trial to be statistically significant. According to the 5% dropout rate, 38 cases need to be selected in the end.

2.样本量分配以及其确定依据
2. Sample size allocation and its determination basis

与本试验的临床试验机构2家，总样本量38例，根据各中心预期病源数、筛选及入组成功率，考虑到中心效应等因素，实际情况可根据统计学原则适当调整。
There are 2 clinical trial institutions in this trial, with a total sample size of 38 cases, and the actual situation can be appropriately adjusted according to statistical principles according to the expected number of disease sources, screening and inclusion power in each center, and considering factors such as center effects.

（二）分析数据集
(2) Analyze the data set

1.全分析集（FAS）
1.Full Analysis Set (FAS).

全分析集为尽可能接近于包括所有随机化的受试者的分析集，通常应包括所有入组且使用过一次器械/接受过一次治疗的受试者，只有在非常有限的情形下才可剔除受试者，包括违反了重要的入组标准、入组后无任何观察数据的情形。
A full set is as close as possible to include all randomized subjects and should generally include all enrolled subjects who have used a single device/received one treatment, and only in very limited cases can participants be excluded, including cases where important enrollment criteria have been violated and there are no observational data after enrollment.

2.符合方案集（PPS）
2.Compliant with the Scheme Set (PPS).

符合方案集是全分析集的子集，包括已接受方案中规定的治疗、可获得主要评价指标的观察数据、对试验方案没有重大违背的受试者。
The conformance set is a subset of the full analysis set and includes subjects who have received the treatment specified in the protocol, have observational data for the main endpoints, and have no significant violations of the trial protocol.

3.安全分析集（SS）
3.Security Analysis Set (SS).

安全性数据集通常应包括所有入组且使用过一次器械/接受过一次治疗并进行过安全性评价的受试者。
Safety datasets should generally include all enrolled subjects who have used a device/received a treatment once and have undergone a safety evaluation.

备注：若从全分析集和符合方案集中剔除受试者，一是需符合方案中的定义，二是需充分阐明剔除理由，需在盲态审核时阐明剔除理由。
Note: If subjects are excluded from the full analysis set and the conformance set, one must meet the definition in the protocol, and the other must fully explain the reason for exclusion, and the reason for exclusion must be clarified during the blind review.

（三）受试者剔除标准
(3) Subject exclusion criteria

出现以下三种情况，需在数据审核阶段讨论后决定是否剔除。
In the following three situations, it is necessary to decide whether to remove them after discussion in the data review stage.

不符合入选标准的受试者；
Subjects who do not meet the inclusion criteria;

符合排除标准的受试者；
Subjects who meet the exclusion criteria;

违背/偏离方案的受试者。
Subjects who violate/deviate from the protocol.

（四）统计方法
(4) Statistical methods

对所有数据进行统计描述，包括基线资料、所有有效性指标以及所有安全性指标等。其中计量资料给出均数、标准差、最小值、最大值、中位数；计数资料给出频数及相应的百分数。
All data were statistically described, including baseline data, all efficacy indicators, and all safety indicators. Among them, the econometric data gives the mean, standard deviation, minimum, maximum and median. The counting data gives the frequency and the corresponding percentage.

主要评价指标采用置信区间法进行优效检验，统计试验器械和对照器械的血小板浓度合格率，计算试验器械-对照器械置信区间的下限CL，若[CL , ∞] 完全在[ ∆, ∞] 范围内，或者CL > ∆，可下优效性的结论。
The main evaluation index was the confidence interval method for the efficiency test, the platelet concentration qualification rate of the test device and the control device was counted, and the lower limit CL of the confidence interval between the test device and the control device was calculated, if [CL, ∞] was completely within the range of [ ∆, ∞], or CL > ∆, which can be used to conclude superiority.

次要评价指标和安全性指标采用差异性检验，计量资料符合正态性及方差齐性者采用t检验，不符合正态性者采用非参数检验，符合正态性不符合方差齐性者采用校正t检验。计数资料采用χ2检验或Fisher exact检验。
The difference test was used for the secondary evaluation indexes and safety indicators, the t-test was used for the normality and variance homogeneity of the measurement data, the non-parametric test was used for the non-normality test, and the corrected t-test was used for the normality and did not conform to the homogeneity of variance. The chi-square test or Fisher exact test was used for counting.

（五）缺失值和异常值的处理
(5) Handling of missing values and outliers

所有缺失、未用或错误数据（包括中途退出和撤出）和不合理数据，将在数据盲态审核阶段，由研究者及生物统计师共同商讨，并最终确定。这些数据处理的统计学基本原则如下：
All missing, unused, or erroneous data (including withdrawals and withdrawals) and unreasonable data will be discussed and finalized by researchers and biostatisticians during the blind data review stage. The basic statistical principles for the processing of these data are as follows:

描述脱落的每一位受试者的详细情况；
Describe the details of each subject who drops out;

基线的缺失数据，可以不进行估计；
Missing data from baseline can be estimated without estimation;

对错误、不合理的数据可当缺失值处理；
Wrong and unreasonable data can be treated as missing values;

对所有安全性指标的缺失值不进行估计。
Missing values for all safety indicators are not estimated.

监查计划
Monitoring plan

1.监查单位
1.Supervision unit

杭州源囊生物科技有限公司
Hangzhou Yuansang Biotechnology Co., Ltd

2.监查时间
2.Monitoring time

受试者入组前期、中期、最后1例受试者完成时，均应对试验进行监查；如遇特殊情况，可进行相应调整。
The trial should be monitored in the early, middle, and last subjects of enrollment. In case of special circumstances, adjustments can be made accordingly.

3.监查流程
3.Monitoring process

了解项目状态：明确临床试验内容、入组情况等；
Understand the project status: clarify the clinical trial content, enrollment, etc.;

预约访问：与研究者和机构办老师预约监查时间，确定监查前研究者和机构已准备好所有相关资料；
Appointment of visit: Make an appointment with the researcher and the teacher of the institution to make sure that the researcher and the institution have prepared all relevant materials before the monitoring.

计划访问：明确监查访问目标；
Planned visits: Clarify the objectives of monitoring visits;

监查内容：检查受试者提前终止情况和记录，检查《病例报告表》的数据与签字情况及签字日期，检查器械及附件耗材的保存情况，检查器械及附件耗材的数量等；
Monitoring content: check the early termination and records of subjects, check the data and signature status and signing date of the "Case Report Form", check the preservation of equipment and accessory consumables, check the quantity of equipment and accessory consumables, etc.;

整理监查结果：整理监查过程中发现的问题并反馈给研究者、机构办老师、协调员；
Sort out the inspection results: sort out the problems found in the monitoring process and feedback them to researchers, institutional teachers, and coordinators;

完成此次监查。
Complete this inspection.

数据管理
Data management

1.数据处理
1.Data processing

数据移交
Data handover

研究者根据受试者的原始记录，将数据及时、完整、正确、清晰地载入电子病例报告表（eCRF）。监查员监查临床试验遵循试验方案进行，确认所有eCRF填写正确完整，并与原始资料保持一致。如有错误和遗漏，应及时要求研究者改正。
The investigator loaded the data into the electronic case report form (eCRF) in a timely, complete, correct and clear manner based on the subject's original records. The monitor monitors that the clinical trial is conducted according to the trial protocol and that all eCRFs are completed correctly and consistent with the original data. If there are any errors or omissions, the researcher should be asked to correct them in time.

数据录入与核查
Data entry and verification

数据录入：
Data entry:

本试验数据录入为直接录入电子数据采集系统，研究者或CRC根据受试者的原始观察记录，将数据及时、完整、正确、清晰地载入电子病例报告表（eCRF）。
The data entry of this trial is directly entered into the electronic data acquisition system, and the investigator or CRC will load the data into the electronic case report form (eCRF) in a timely, complete, correct and clear manner based on the subject's original observation records.

监查员监查试验的进行是否遵循试验方案。确认所有eCRF填写正确完整，并与原始资料一致。如有错误和遗漏，及时要求研究者或CRC改正。EDC系统将记录所有稽查轨迹。
The supervisor supervises whether the test is carried out in accordance with the test plan. Verify that all eCRFs are completed correctly and consistent with the original materials. If there are any errors and omissions, ask the researcher or CRC to correct them in time. The EDC system will record all audit tracks.

经过监查员检查后的eCRF，由监查员和研究者进行确认。
The eCRF after being checked by the monitor is confirmed by the monitor and the investigator.

数据核查
Data verification

EDC系统上线之前，所有的计算机程序核查都需通过用户测试。受试者入组过程中，将对数据进行实时的数据核查，数据核查后产生的质疑将直接在EDC系统发给研究中心，研究者或CRC完成答疑，实时进行数据核查和清理，直至最后各方确认锁定数据。
Before the EDC system goes live, all computer program verification needs to pass user testing. During the enrollment process of subjects, the data will be verified in real time, and the doubts generated after the data verification will be sent directly to the research center in the EDC system, and the investigator or CRC will complete the Q&A, and the data will be verified and cleaned in real time until the final parties confirm the locked data.

所有临床试验数据均按要求记录于EDC中，数据管理员在数据库锁定前，核对EDC中所有数据，确保数据的准确性。
All clinical trial data is recorded in the EDC as required, and the data manager checks all data in the EDC to ensure the accuracy of the data before the database is locked.

数据管理员应按各指标数值的范围和相互关系拟定数据范围检查和逻辑检查内容，并编写相应的计算机程序，在输入前控制错误数据输入，找出错误原因加以改正，所有错误内容及修改结果应有记录并妥善保存。
The data manager should formulate the data range check and logical check content according to the range and relationship between the values of each indicator, and write the corresponding computer program to control the wrong data input before entering, find out the cause of the error and correct it, and all the error content and modification results should be recorded and properly stored.

电子病例报告表（eCRF）在按要求完成数据录入和核查后，按要求进行保存，以备查考。电子数据文件包括数据库、检查程序和说明文件等，应分类保存，并有多个备份保存于不同磁盘或记录介质上，妥善保存，防止损坏。
The electronic case report form (eCRF) is kept as required for future use after data entry and verification are completed as required. Electronic data files, including databases, inspection procedures and instruction files, should be stored in categories, and multiple backups should be stored on different disks or recording media to prevent damage.

经对数据库数据进行核对和评价，确认无误后，锁定数据库。数据锁定之后发现的问题，其确认及修改应有详细记录。
After checking and evaluating the database data and confirming that it is correct, the database is locked. The confirmation and modification of problems found after data locking should be recorded in detail.

2.记录保存
2.Record keeping

临床试验过程中，研究者和申办者需要完成如下记录：
During the clinical trial, the investigator and sponsor are required to complete the following records:

在临床试验中，研究者应当确保将任何观察与发现均正确完整地予以记录，并认真填写病例报告表。
In clinical trials, researchers should ensure that any observations and findings are recorded correctly and completely, and that case report forms are carefully completed.

临床试验记录作为原始资料，不得随意更改；确需作更改时应当说明理由，签名并注明日期。对显著偏离临床试验方案或者在临床可接受范围以外的数据应当加以核实，由研究者作必要的说明。
Clinical trial records shall be used as original data and shall not be changed at will; If it is really necessary to make changes, the reasons shall be explained, signed and dated. Data that significantly deviates from the clinical trial protocol or is outside the clinically acceptable range should be verified, and the researcher should make necessary explanations.

申办者应当准确、完整地记录与临床试验相关的信息，内容包括：（一）试验用医疗器械运送和处理记录，包括名称、型号、规格、批号或者序列号，接收人的姓名、地址，运送日期，退回维修或者临床试验后医疗器械样品回收与处置日期、原因和处理方法等；（二）与临床试验机构签订的协议；（三）监查报告、核查报告；（四）严重不良事件和可能导致严重不良事件的器械缺陷的记录与报告。
The sponsor shall accurately and completely record the information related to the clinical trial, including: (1) Records of transportation and handling of the experimental medical device, including name, model, specification, batch number or serial number, name and address of the recipient, date of delivery, return of medical device samples for repair or clinical trial, date of recovery and disposal of medical device samples after clinical trials, reasons and disposal methods, etc.; (2) Agreements signed with clinical trial institutions; (3) Supervision reports and verification reports; (4) Records and reports of serious adverse events and device defects that may cause serious adverse events.

伦理委员会、临床试验机构和申办者应该保存临床试验资料的年限如下：
Ethics committees, clinical trial sites, and sponsors should retain clinical trial data for the following periods of time:

伦理委员会应当保留全部有关记录至临床试验完成后至少10年；
The ethics committee shall retain all relevant records until at least 10 years after the completion of the clinical trial.

临床试验机构应当保存临床试验资料至临床试验结束后10年；
Clinical trial institutions shall keep clinical trial data until 10 years after the end of clinical trials.

申办者应当保存临床试验资料至无该医疗器械使用时。
The sponsor shall preserve the clinical trial data until the medical device is not in use.

风险受益分析
Risk-benefit analysis

1.受益分析
1.Benefit analysis

试验器械被认定为浙江省第二类创新医疗器械，产品质量过关，满足临床试验要求；试验器械已经通过国家药品监督管理局指定的产品注册检验，检验结果为合格。
The test device was recognized as a Class II innovative medical device in Zhejiang Province, and the product quality passed the test and met the requirements of clinical trials. The test equipment has passed the product registration inspection designated by the State Medical Products Administration, and the test result is qualified.

承担本试验的临床机构，均拥有完备的仪器、设备及技术资源。
The clinical institutions undertaking this trial have complete instruments, equipment and technical resources.

研究者具有丰富的临床试验经验，已经过GCP及相关培训，能严格按临床试验方案进行治疗。
The investigator has rich clinical trial experience, has GCP and related training, and can strictly follow the clinical trial protocol for treatment.

2. 风险分析
2. Risk analysis

符合方案集病例数少于统计学要求的36例；
36 cases met the protocol set with fewer than the statistical requirements;

未严格按照操作规范进行操作，可能造成本次临床试验的失败；
failure to operate in strict accordance with the operating specifications may cause the failure of this clinical trial;

未严格执行临床试验方案，可能造成本次临床试验的失败；
failure to strictly implement the clinical trial protocol may cause the failure of this clinical trial;

如果试验产品性能出现非预期的改变，则临床试验可能失败。
If there is an unintended change in the performance of the trial product, the clinical trial may fail.

十、临床试验的质量控制
10. Quality control of clinical trials

各试验机构应按标准操作规程和质量控制程序进行临床操作；
Each experimental institution shall conduct clinical operations in accordance with standard operating procedures and quality control procedures;

随机、平行对照等原则可以减少选择性偏倚，使基线均衡，从而具有可比性；
Principles such as random and parallel control can reduce selective bias and make the baseline equilibrium, so that it is comparable.

试验开始前，对参入临床试验的研究者进行充分培训，确保研究者充分了解试验流程且熟悉器械使用方法；
Before the start of the trial, fully train the researchers participating in the clinical trial to ensure that the researchers fully understand the trial process and are familiar with the use of the device.

研究过程中，临床监查员严格按照监查计划进行监查，保证临床方案的所有内容都得到严格遵守，研究资料得到及时正确的填写；
During the research process, the clinical monitor strictly follows the monitoring plan to ensure that all contents of the clinical protocol are strictly complied with and the research materials are filled in in a timely and correct manner.

临床试验数据严格执行数据管理过程。
Clinical trial data strictly implements the data management process.

十一、临床试验的伦理问题以及知情同意
11. Ethical issues of clinical trials and informed consent

（一）伦理方面的考虑
(1) Ethical considerations

本临床试验遵循《赫尔辛基宣言》，并严格按照中国《医疗器械临床试验质量管理规范》中的规定开展临床试验。
This clinical trial is conducted in accordance with the Declaration of Helsinki and in strict accordance with the provisions of China's Good Practice for Clinical Trials of Medical Devices.

（二）知情同意过程
(2) Informed consent process

已根据方案准备好知情同意书文本，具体内容见《知情同意书》样本。
The text of the informed consent form has been prepared according to the protocol, and the specific content is shown in the sample "Informed Consent Form".

受试者知情同意过程注意事项：
Precautions for the subject's informed consent process:

研究者或委派的负责人执行知情同意过程；
Perform the informed consent process by the investigator or delegated principal;

知情同意过程应包含与目标受试者做出决定（是否参加临床试验）相关的每个方面；
The informed consent process should encompass each aspect related to the target subject's decision (whether to participate in a clinical trial);

应避免对目标受试者强迫、诱导或施加不恰当的影响；
Coercion, induction, or inappropriate influence on the target subject should be avoided;

目标受试者有权保留自己的法律权益；
The target subject has the right to retain his or her legal rights and interests;

使用目标受试者的母语进行易懂的非专业描述，便于目标受试者理解；
Easy-to-understand non-professional descriptions in the native language of the target subjects for easy understanding;

提供足够的时间供目标受试者阅读并理解《知情同意书》，并考虑是否参加临床试验；
Provide sufficient time for the target subjects to read and understand the Informed Consent Form and consider whether to participate in the clinical trial;

应包含目标受试者及研究者或研究者委派负责人的个人签名；
It should contain the personal signatures of the target subject and the investigator or the investigator's designated principal;

应给受试者提供一份有签名及日期的《知情同意书》；
Subjects should be provided with a signed and dated "Informed Consent Form";

应说明在受试者无法自行处理等特殊情况下如何获得并填写《知情同意书》；
It should explain how to obtain and fill in the "Informed Consent Form" in special cases such as the subject cannot handle it on their own;

确保整个临床试验过程中将重要的新信息提供给新加入的以及当前的受试者。
Ensure that important new information is made available to new and current participants throughout the clinical trial process.

十二、对不良事件和器械缺陷报告的规定
12. Regulations on adverse events and device defect reporting

（一）不良事件和器械缺陷的定义和报告规定
(1) Definition and reporting provisions for adverse events and device defects

不良事件，是指在临床试验过程中出现的不利的医学事件，无论是否与试验用医疗器械相关。
Adverse events are adverse medical events that occur during a clinical trial, whether or not related to the investigational medical device.

器械缺陷，是指临床试验过程中医疗器械在正常使用情况下存在可能危及人体健康和生命安全的不合理风险，如标签错误、质量问题、故障等。
Device defects refer to unreasonable risks that may endanger human health and life safety under normal use of medical devices during clinical trials, such as labeling errors, quality problems, failures, etc.

研究者应当记录临床试验过程中发生的所有不良事件和发现的器械缺陷，并与申办者共同分析事件原因，形成书面分析报告，提出继续、暂停或者终止试验的意见，经临床试验机构医疗器械临床试验管理部门报伦理委员会审查。
The investigator shall record all adverse events and device defects found during the clinical trial, and jointly analyze the cause of the event with the sponsor, form a written analysis report, and put forward opinions on continuing, suspending or terminating the trial, which shall be reported to the ethics committee by the clinical trial institution's medical device clinical trial management department.

如果发现试验用医疗器械预期以外的不良事件时，研究者和申办者共同对知情同意书相关内容进行修改，按照相关工作程序报伦理委员会审查同意后，由受影响的受试者或者其监护人对修改后的知情同意书进行重新签名确认。
If unexpected adverse events are found in the investigational medical device, the investigator and the sponsor will jointly modify the relevant content of the informed consent form, and after reporting to the ethics committee for review and consent in accordance with the relevant working procedures, the affected subject or his/her guardian will re-sign and confirm the revised informed consent form.

在本试验中可能出现的不良事件及处理方法：
Possible adverse events in this trial and how to manage them:

器械缺陷，及时更换受试器械。
If the equipment is defective, replace the tested instrument in time.

创面手术部位局部出现剧烈疼痛、麻木、瘙痒的事件发生，研究者应根据情况给予针对性治疗缓解症状。
If severe pain, numbness, and itching occur locally at the surgical site of the wound, the investigator should give targeted treatment to relieve symptoms according to the situation.

创面手术部位局部出现大量渗液，伤口周围红肿，皮温升高，渗出液涂片出现脓球，应考虑为感染，研究者应根据情况给予局部疗法和/或全身疗法。
Localized large exudate at the surgical site of the wound, redness and swelling around the wound, increased skin temperature, and pus balls on the exudate smear should be considered as infection, and the investigator should give local and/or systemic therapy according to the situation.

申办方根据相关要求购买“临床试验责任保险”，以保障受试者权益。
The sponsor shall purchase "clinical trial liability insurance" according to relevant requirements to protect the rights and interests of subjects.

（三）严重不良事件的定义
(3) Definition of serious adverse events

严重不良事件，是指临床试验过程中发生的导致死亡或者健康状况严重恶化，包括致命的疾病或者伤害、身体结构或者身体功能的永久性缺陷、需住院治疗或者延长住院时间、需要进行医疗或者手术介入以避免对身体结构或者身体功能造成永久性缺陷；导致胎儿窘迫、胎儿死亡或者先天性异常、先天缺损等事件。
Serious adverse events refer to deaths or serious deterioration of health conditions that occur during clinical trials, including fatal diseases or injuries, permanent defects in body structure or body function, hospitalization or prolongation of hospitalization, and medical or surgical intervention to avoid permanent defects in body structure or body function. Causes fetal distress, fetal death, congenital anomalies, birth defects and other events.

（四）报告程序、联络人信息
(4) Reporting procedures and contact person information

试验过程中发生的任何严重不良事件和可能导致严重不良事件的器械缺陷（不论是否与试验用医疗器械有关），都必须报告。在临床试验中出现严重不良事件的，研究者应当立即对受试者采取适当的治疗措施，同时24小时内书面报告所属的临床试验机构医疗器械临床试验管理部门，并经其书面通知申办者和相应的伦理委员会。对于严重不良事件和可能导致严重不良事件的器械缺陷，申办者应当在获知后15天内向所备案的药品监督管理部门和同级卫生计生主管部门报告，同时应当向参与试验的其他临床试验机构和研究者通报，并经其医疗器械临床试验管理部门及时通知该临床试验机构的伦理委员会。对于死亡事件，申办者应当在获知后7天内向所备案的药品监督管理部门和同级卫生计生主管部门报告，同时应当向参与试验的其他临床试验机构和研究者通报，并经其医疗器械临床试验管理部门及时通知该临床试验机构的伦理委员会。
Any serious adverse events that occur during the course of the trial and device defects that may cause serious adverse events (whether or not related to the investigational medical device) must be reported. If serious adverse events occur in clinical trials, the investigator shall immediately take appropriate treatment measures for the subject, and at the same time report in writing to the clinical trial management department of the clinical trial institution within 24 hours, and notify the sponsor and the corresponding ethics committee in writing. For serious adverse events and device defects that may lead to serious adverse events, the sponsor shall report to the filed drug regulatory department and the health and family planning department at the same level within 15 days after being notified, and shall also notify other clinical trial institutions and researchers participating in the trial, and promptly notify the ethics committee of the clinical trial institution through its medical device clinical trial management department. For deaths, the sponsor shall report to the filed drug regulatory department and the health and family planning department at the same level within 7 days after being notified, and shall notify other clinical trial institutions and researchers participating in the trial, and promptly notify the ethics committee of the clinical trial institution through its medical device clinical trial management department.

申办者应当准确、完整地记录严重不良事件和可能导致严重不良事件的器械缺陷的记录与报告。
The sponsor shall accurately and completely record and report serious adverse events and device defects that may cause serious adverse events.

研究单位及联系方式： 浙江大学医学院附属邵逸夫医院 0571-86006987
Research unit and contact information: Run Shaw Hospital Affiliated to Zhejiang University School of Medicine 0571-86006987

      宁波市第六医院 0574-89007390
Ningbo Sixth Hospital 0574-89007390

申办者及联系方式： 杭州源囊生物科技有限公司 0571-88313603
Sponsor and contact information: Hangzhou Yuannang Biotechnology Co., Ltd. 0571-88313603

十三、临床试验方案的偏离与临床试验方案修正的规定
13. Provisions on deviations from clinical trial protocols and amendments to clinical trial plans

若本方案在临床试验实际执行过程中出现问题，需要对本方案进行修订，应向申办者提出，经多中心协商讨论，由负责单位对方案做出修订，以书面形式提交申办方和各参研单位认可，再次报请伦理委员会批准后实施。
If there are problems in the actual implementation of the clinical trial and it is necessary to revise the plan, it should be proposed to the sponsor, and after consultation and discussion by the multi-center, the responsible unit will make revisions to the plan, submit it in writing to the sponsor and all participating units for approval, and then report to the ethics committee for approval before implementation.

对不影响受试者权益、安全和健康，或者与临床试验目的或终点不相关的非实质性改变无需事前报告，但事后应当书面告知伦理委员会。
Non-substantive changes that do not affect the rights and interests, safety and health of subjects, or are not related to the purpose or endpoints of the clinical trial do not need to be reported in advance, but should be notified in writing to the Ethics Committee afterwards.

影响受试者权益、安全和健康或者临床试验科学性的临床试验方案偏离，包括请求偏离和报告偏离。为保护受试者权益、安全和健康，在紧急情况下发生的偏离无法及时报告的，应当在事后以书面形式尽快按照相关规定报告。
Deviations from clinical trial protocols that affect the rights and interests, safety, and health of the subject, or the scientific nature of clinical trials, including deviations from requests and reports. In order to protect the rights and interests, safety and health of subjects, if deviations that occur in an emergency cannot be reported in a timely manner, they shall be reported in writing as soon as possible in accordance with relevant regulations afterwards.

十四、直接访问源数据、文件
14. Direct access to source data and files

临床试验所有源数据记录于受试者住院病历中，通过查阅相关文件即可访问源数据。
All source data from clinical trials are recorded in the subject's inpatient medical record, and the source data can be accessed by consulting relevant documents.

十五、临床试验报告应当涵盖的内容
15. The content that the clinical trial report should cover

临床试验报告涵盖的内容参见《医疗器械临床试验质量管理规范》（2022年21号）医疗器械临床试验报告范本。
For the content covered by the clinical trial report, please refer to the "Good Management Code for Medical Device Clinical Trials" (2022 No. 1) Medical device clinical trial report template.

十六、保密原则
16. Principle of confidentiality

所有在试验中收集到的受试者的信息都将根据法律规定的程度进行保密。在研究记录中，受试者将有一个标识编号。受试者的个人信息在没有受试者的书面许可的情况下是不会公布的。但是受试者的记录有可能被研究者，其主要代理商，以及中国国家药品监督管理局或有关国家医疗器械注册管理机构审查。此项试验的内容有可能发表，不过受试者的个人信息在任何刊物上都将是保密的。
All information collected on subjects in the trial will be kept confidential to the extent required by law. In the study record, the subject will have an identification number. Subjects' personal information will not be released without the subject's written permission. However, the subject's records may be reviewed by the investigator, its principal agent, and the National Medical Products Administration of China or the relevant national medical device registry. The content of this trial may be published, but the personal information of the subjects will be kept confidential in any publication.

研究者必须对研究的结果，方案等资料严格保密，除非经过申办者书面授权，否则禁止自行发布。如有引用，也必须提前得到申办者书面授权。
Researchers must keep the research results, plans and other information strictly confidential, and self-publishing is prohibited unless authorized in writing by the sponsor. If cited, it must also be authorized in writing by the sponsor in advance.

十七、各方承担的职责
17. Responsibilities of all parties

（一）申办方职责
(1) Responsibilities of the sponsor

申办者负责发起、申请、组织、监查临床试验，并对临床试验的真实性、可靠性负责。
The sponsor is responsible for initiating, applying, organizing, and monitoring clinical trials, and is responsible for the authenticity and reliability of clinical trials.

申办者负责组织制定和修改研究者手册、临床试验方案、知情同意书、病例报告表、有关标准操作规程以及其他相关文件，并负责组织开展临床试验所必需的培训。
The sponsor is responsible for organizing the development and revision of investigator manuals, clinical trial protocols, informed consent, case report forms, relevant standard operating procedures, and other relevant documents, and is responsible for organizing the training necessary for conducting clinical trials.

申办者应当根据试验用医疗器械的特性，在经资质认定的医疗器械临床试验机构中选择试验机构及其研究者。申办者在与临床试验机构签署临床试验协议前，应当向临床试验机构和研究者提供最新的研究者手册以及其他相关文件，以供其决定是否可以承担该项临床试验。
The sponsor shall select the testing institution and its researchers among the qualified medical device clinical trial institutions according to the characteristics of the experimental medical device. Before signing a clinical trial agreement with the clinical trial site, the sponsor shall provide the clinical trial site and the investigator with the latest investigator's manual and other relevant documents for them to decide whether they can undertake the clinical trial.

申办者在组织临床试验方案的制定中不得夸大宣传试验用医疗器械的机理和疗效。
The sponsor shall not exaggerate the mechanism and efficacy of the experimental medical device in organizing the formulation of the clinical trial plan.

在临床试验过程中，申办者得到影响临床试验的重要信息时，应当及时对研究者手册以及相关文件进行修改，并通过临床试验机构的医疗器械临床试验管理部门提交伦理委员会审查同意。
During the clinical trial, when the sponsor obtains important information affecting the clinical trial, it shall promptly revise the investigator's manual and relevant documents, and submit it to the ethics committee for review and approval through the medical device clinical trial management department of the clinical trial institution.

申办者应当与临床试验机构和研究者就临床试验的相关细则达成书面协议。
The sponsor shall reach a written agreement with the clinical trial institution and the investigator on the relevant details of the clinical trial.

申办者对试验用医疗器械在临床试验中的安全性负责。当发现可能影响受试者安全或者试验实施可能改变伦理委员会对继续试验的批准情况时，申办者应当立即通知所有临床试验机构和研究者，并做出相应处理。
The sponsor is responsible for the safety of the investigational medical device in clinical trials. Sponsors should immediately notify all clinical trial sites and investigators and take appropriate action when it is found that it may affect the safety of the subjects or that the conduct of the trial may change the approval of the Ethics Committee to continue the trial.

申办者决定暂停或者终止临床试验的，应当在5日内通知所有临床试验机构医疗器械临床试验管理部门，并书面说明理由。临床试验机构医疗器械临床试验管理部门应当及时通知相应的研究者、伦理委员会。对暂停的临床试验，未经伦理委员会同意，不得恢复。
If the sponsor decides to suspend or terminate the clinical trial, it shall notify the medical device clinical trial management department of all clinical trial institutions within 5 days and explain the reasons in writing. The clinical trial management department of the clinical trial institution shall promptly notify the corresponding researchers and ethics committees. Clinical trials that have been suspended shall not be resumed without the consent of the Ethics Committee.

申办者应当保证实施临床试验的所有研究者严格遵循临床试验方案，发现临床试验机构和研究者不遵从有关法律法规、本规范和临床试验方案的，应当及时指出并予以纠正；如情况严重或者持续不改，应当终止试验，并向临床试验机构所在地省、自治区、直辖市药品监督管理部门和国家药品监督管理局报告。
The sponsor shall ensure that all researchers conducting clinical trials strictly follow the clinical trial plan, and if clinical trial institutions and researchers are found to be in compliance with relevant laws and regulations, this specification and clinical trial plan, they shall promptly point out and correct them; If the situation is serious or persistent, the trial shall be terminated and reported to the drug administration department of the province, autonomous region or municipality directly under the Central Government where the clinical trial institution is located and the State Medical Products Administration.

申办者应当为发生与临床试验相关的伤害或者死亡的受试者承担治疗的费用以及相应的经济补偿，但在诊疗活动中由医疗机构及其医务人员过错造成的损害除外。
The sponsor shall bear the cost of treatment and corresponding financial compensation for subjects who suffer injuries or deaths related to clinical trials, except for damages caused by the fault of medical institutions and their medical staff during diagnosis and treatment activities.

申办者应当对临床试验承担监查责任，并选择符合要求的监查员履行监查职责。
The sponsor shall assume the responsibility for monitoring the clinical trial and select a supervisor who meets the requirements to perform the monitoring duties.

申办者为保证临床试验的质量，可以组织独立于临床试验、并具有相应培训和经验的核查员对临床试验开展情况进行核查，评估临床试验是否符合试验方案的要求。
In order to ensure the quality of clinical trials, the sponsor may organize verifiers independent of clinical trials with corresponding training and experience to verify the development of clinical trials and evaluate whether the clinical trials meet the requirements of the trial protocol.

对于严重不良事件和可能导致严重不良事件的器械缺陷，申办者应当在获知后5个工作日内向所备案的药品监督管理部门和同级卫生计生主管部门报告，同时应当向参与试验的其他临床试验机构和研究者通报，并经其医疗器械临床试验管理部门及时通知该临床试验机构的伦理委员会。
For serious adverse events and device defects that may lead to serious adverse events, the sponsor shall report to the filed drug regulatory department and the health and family planning department at the same level within 5 working days after being notified, and shall notify other clinical trial institutions and researchers participating in the trial, and promptly notify the ethics committee of the clinical trial institution through its medical device clinical trial management department.

对于多中心临床试验，申办者应当保证在临床试验前已制定文件，明确协调研究者和其他研究者的职责分工。
For multicenter clinical trials, the sponsor should ensure that documents have been developed before the clinical trial to clearly coordinate the division of responsibilities between the investigator and other investigators.

对于多中心临床试验，申办者应当按照临床试验方案组织制定标准操作规程，并组织对参与试验的所有研究者进行临床试验方案和试验用医疗器械使用和维护的培训，确保在临床试验方案执行、试验用医疗器械使用方面的一致性。
For multi-center clinical trials, the sponsor shall organize the formulation of standard operating procedures in accordance with the clinical trial protocol, and organize training for all researchers participating in the trial on the use and maintenance of clinical trial protocols and experimental medical devices to ensure consistency in the implementation of the clinical trial protocol and the use of experimental medical devices.

在多中心临床试验中，申办者应当保证病例报告表的设计严谨合理，能够使协调研究者获得各分中心临床试验机构的所有数据。
In multicenter clinical trials, sponsors should ensure that the case report form is designed to be rigorous and reasonable to enable the coordinating investigator to obtain all data from each sub-center clinical trial site.

（二）临床试验机构和研究者职责
(2) Responsibilities of clinical trial institutions and investigators

临床试验机构在接受临床试验前，应当根据试验用医疗器械的特性，对相关资源进行评估，以决定是否接受该临床试验。
Before accepting a clinical trial, the clinical trial institution shall evaluate the relevant resources according to the characteristics of the experimental medical device to decide whether to accept the clinical trial.

临床试验机构应当按照与申办者的约定妥善保存临床试验记录和基本文件。
The clinical trial institution shall properly keep clinical trial records and basic documents in accordance with the agreement with the sponsor.

负责临床试验的研究者应当具备下列条件：在该临床试验机构中具有副主任医师、副教授、副研究员等副高级以上相关专业技术职称和资质；具有试验用医疗器械所要求的专业知识和经验，必要时应当经过有关培训；熟悉申办者要求和其所提供的与临床试验有关的资料、文献；有能力协调、支配和使用进行该项试验的人员和设备，且有能力处理试验用医疗器械发生的不良事件和其他关联事件；熟悉国家有关法律、法规以及本规范。
The investigator in charge of the clinical trial shall meet the following conditions: have relevant professional and technical titles and qualifications such as deputy chief physician, associate professor, and associate researcher in the clinical trial institution; Have the professional knowledge and experience required for experimental medical devices, and undergo relevant training when necessary; Familiar with the requirements of the sponsor and the information and literature related to the clinical trial provided by him; Ability to coordinate, control and use the personnel and equipment to conduct the trial, and ability to handle adverse events and other related events of the investigational medical device; Familiar with relevant national laws, regulations and this code.

临床试验前，临床试验机构的医疗器械临床试验管理部门应当配合申办者向伦理委员会提出申请，并按照规定递交相关文件。
Before clinical trials, the clinical trial management department of the clinical trial institution shall cooperate with the sponsor to submit an application to the ethics committee and submit relevant documents in accordance with regulations.

研究者应当确保参与试验的有关工作人员熟悉试验用医疗器械的原理、适用范围、产品性能、操作方法、安装要求以及技术指标，了解该试验用医疗器械的临床前研究资料和安全性资料，掌握临床试验可能产生风险的防范以及紧急处理方法。
The researcher shall ensure that the relevant staff participating in the trial are familiar with the principle, scope of application, product performance, operation method, installation requirements and technical indicators of the experimental medical device, understand the preclinical research data and safety data of the experimental medical device, and master the prevention and emergency treatment methods of possible risks in the clinical trial.

研究者应当保证所有临床试验参与人员充分了解临床试验方案、相关规定、试验用医疗器械特性以及与临床试验相关的职责，并确保有足够数量并符合临床试验方案入选标准的受试者进入临床试验、确保有足够的时间在协议约定的试验期内，按照相关规定安全地实施和完成临床试验。
The investigator shall ensure that all clinical trial participants fully understand the clinical trial protocol, relevant regulations, characteristics of the experimental medical device and responsibilities related to the clinical trial, and ensure that a sufficient number of subjects who meet the selection criteria of the clinical trial protocol enter the clinical trial, and ensure that there is sufficient time to safely conduct and complete the clinical trial in accordance with the relevant regulations within the trial period agreed in the agreement.

研究者应当保证将试验用医疗器械只用于该临床试验的受试者，并不得收取任何费用。
The investigator shall ensure that the investigational medical device is used only for the subject of the clinical trial and shall not charge any fee.

研究者应当严格遵循临床试验方案，未经申办者和伦理委员会的同意，或者未按照规定经国家药品监督管理局批准，不得偏离方案或者实质性改变方案。但在受试者面临直接危险等需要立即消除的紧急情况下，也可以事后以书面形式报告。
Researchers should strictly follow the clinical trial protocol and shall not deviate from the protocol or substantively change the protocol without the consent of the sponsor and the ethics committee, or without the approval of the NMPA in accordance with regulations. However, in the event of an emergency that needs to be eliminated immediately, such as when the subject is in immediate danger, it can also be reported in writing afterwards.

研究者负责招募受试者、与受试者或者其监护人谈话。研究者有责任向受试者说明试验用医疗器械以及临床试验有关的详细情况，告知受试者可能的受益和已知的、可以预见的风险，并取得受试者或者其监护人签字和注明日期的知情同意书。
The investigator is responsible for recruiting the subject and talking to the subject or their guardian. The investigator is responsible for explaining the details of the investigational medical device and the clinical trial to the subject, informing the subject of the possible benefits and known foreseeable risks, and obtaining signed and dated informed consent from the subject or his/her guardian.

研究者或者参与试验的其他人员，不应当强迫或者以其他不正当方式诱使受试者参加试验。
The investigator or other personnel participating in the trial should not force or induce the subject to participate in the trial in other improper ways.

研究者在临床试验中发现试验用医疗器械预期以外的不良事件时，应当和申办者共同对知情同意书相关内容进行修改，按照相关工作程序报伦理委员会审查同意后，由受影响的受试者或者其监护人对修改后的知情同意书进行重新签名确认。
If the investigator finds unexpected adverse events of the investigational medical device in the clinical trial, the investigator shall jointly revise the relevant content of the informed consent form with the sponsor, and after reporting to the ethics committee for review and consent in accordance with the relevant working procedures, the affected subject or his/her guardian shall re-sign and confirm the revised informed consent form.

研究者负责做出与临床试验相关的医疗决定，在发生与临床试验相关的不良事件时，临床试验机构和研究者应当保证为受试者提供足够、及时的治疗和处理。当受试者出现并发疾病需要治疗和处理时，研究者应当及时告知受试者。
The investigator is responsible for making medical decisions related to the clinical trial, and in the event of adverse events related to the clinical trial, the clinical trial institution and the investigator shall ensure that adequate and timely treatment and treatment are provided to the subject. When the subject has a concurrent disease requiring treatment and management, the investigator should inform the subject in time.

在临床试验中出现严重不良事件的，研究者应当立即对受试者采取适当的治疗措施，同时书面报告所属的临床试验机构医疗器械临床试验管理部门，并经其书面通知申办者。医疗器械临床试验管理部门应当在24小时内书面报告相应的伦理委员会以及临床试验机构所在地省、自治区、直辖市药品监督管理部门和卫生计生主管部门。对于死亡事件，临床试验机构和研究者应当向伦理委员会和申办者提供所需要的全部资料。
If serious adverse events occur in clinical trials, the investigator shall immediately take appropriate treatment measures for the subject, and at the same time report in writing to the medical device clinical trial management department of the clinical trial institution to which it belongs, and notify the sponsor in writing. The medical device clinical trial management department shall report in writing to the corresponding ethics committee, the drug regulatory department of the province, autonomous region, or municipality where the clinical trial institution is located, and the competent department of health and family planning within 24 hours. For deaths, clinical trial sites and investigators should provide all required information to the ethics committee and sponsors.

研究者应当记录临床试验过程中发生的所有不良事件和发现的器械缺陷，并与申办者共同分析事件原因，形成书面分析报告，提出继续、暂停或者终止试验的意见，经临床试验机构医疗器械临床试验管理部门报伦理委员会审查。
The investigator shall record all adverse events and device defects found during the clinical trial, and jointly analyze the cause of the event with the sponsor, form a written analysis report, and put forward opinions on continuing, suspending or terminating the trial, which shall be reported to the ethics committee by the clinical trial institution's medical device clinical trial management department.

研究者应当保证将临床试验数据准确、完整、清晰、及时地载入病例报告表。病例报告表由研究者签署姓名，任何数据的更改均应当由研究者签名并标注日期，同时保留原始记录，原始记录应当清晰可辨识。
Researchers should ensure that clinical trial data are included in the case report form accurately, completely, clearly, and in a timely manner. The case report form should be signed by the investigator's name, and any changes to the data should be signed and dated by the researcher, while the original record should be kept and the original record should be clearly identifiable.

临床试验机构和研究者应当确保临床试验所形成数据、文件和记录的真实、准确、清晰、安全。
Clinical trial institutions and researchers shall ensure that the data, documents, and records formed by clinical trials are true, accurate, clear, and secure.

临床试验机构和研究者应当接受申办者的监查、核查以及伦理委员会的监督，并提供所需的与试验有关的全部记录。药品监督管理部门、卫生计生主管部门派检查员开展检查的，临床试验机构和研究者应当予以配合。
Clinical trial sites and investigators shall be monitored, verified, and supervised by the Ethics Committee by the sponsor and provide all required records related to the trial. Where the drug administration department or the competent department of health and family planning dispatches inspectors to carry out inspections, clinical trial institutions and researchers shall cooperate.

临床试验机构和研究者发现风险超过可能的受益，或者已经得出足以判断试验用医疗器械安全性和有效性的结果等，需要暂停或者终止临床试验时，应当通知受试者，并保证受试者得到适当治疗和随访，同时按照规定报告，提供详细书面解释。必要时，报告所在地省、自治区、直辖市药品监督管理部门。
When clinical trial institutions and researchers find that the risks outweigh the possible benefits, or have reached results sufficient to judge the safety and efficacy of the experimental medical device, and need to suspend or terminate the clinical trial, they shall notify the subjects and ensure that the subjects receive appropriate treatment and follow-up, and at the same time report in accordance with the regulations and provide detailed written explanations. If necessary, report to the drug supervision and administration department of the province, autonomous region or municipality directly under the Central Government.

临床试验机构和研究者对申办者违反有关规定或者要求改变试验数据、结论的，应当向申办者所在地省、自治区、直辖市药品监督管理部门或者国家药品监督管理局报告。
Clinical trial institutions and researchers shall report to the drug administration department of the province, autonomous region, or municipality directly under the Central Government where the sponsor is located or the State Medical Products Administration if the sponsor violates relevant regulations or requests to change the trial data or conclusions.

临床试验结束时，研究者应当确保完成各项记录、报告。同时，研究者还应当确保收到的试验用医疗器械与所使用的、废弃的或者返还的数量相符合，确保剩余的试验用医疗器械妥善处理并记录存档。
At the end of the clinical trial, the investigator should ensure that all records and reports are completed. At the same time, researchers should also ensure that the experimental medical devices received match the quantity used, discarded or returned, and ensure that the remaining experimental medical devices are properly disposed of and documented.

研究者可以根据临床试验的需要，授权相应人员进行受试者招募、与受试者持续沟通、临床试验数据记录、试验用医疗器械管理等。研究者应当对其授权的人员进行相关的培训并形成相应的文件。
Researchers can authorize corresponding personnel to recruit subjects, continuously communicate with subjects, record clinical trial data, and manage experimental medical devices according to the needs of clinical trials. Researchers should conduct relevant training for their authorized personnel and form corresponding documents.

研究者申明
Researchers declare

我同意：
I agree:

严格按照赫尔辛基宣言、中国现行法规、以及临床试验方案的要求进行本次临床试验。
This clinical trial was conducted in strict accordance with the requirements of the Declaration of Helsinki, current regulations in China, and the clinical trial protocol.

将所有要求的全部数据准确记录于病例报告表（CRF）中，按时完成临床试验报告。
All required data are accurately recorded in the case report form (CRF) to complete the clinical trial report on time.

试验器械仅用于本次临床试验，在临床试验过程中完整准确地记录试验器械的接受和使用情况，并保持记录。
The test device is only used for this clinical trial, and the acceptance and use of the test device are completely and accurately recorded during the clinical trial process, and records are maintained.

允许申办者授权或派遣的监查员、核查员和监管部门对该项临床试验进行监査、核查和检查。
Inspectors, verifiers, and regulatory authorities authorized or dispatched by the sponsor are allowed to monitor, verify, and inspect the clinical trial.

严格履行各方签署的临床试验合同/协议条款。
Strictly implement the terms of the clinical trial contract/agreement signed by all parties.

我已全部阅读了临床试验方案，包括以上的申明，我同意以上全部内容。
I have read the clinical trial protocol in its entirety, including the above statements, and I agree with all of the above.