A Multicenter, Randomized, Double-blind, Positive-control, Non-inferiority Clinical Trial on the Effectiveness and Safety of HCA-N Solution for the Preservation of Kidney Grafts During Kidney Transplantation

Study Title：A Multicenter, Randomized, Double-Blind, Positive-Controlled, Non-Inferiority Clinical Trial to Evaluate the Efficacy and Safety of HCA-N Solution for Preservation of Donor Kidneys in Renal Transplantation Study Design：Multicenter, randomized, double-blind, positive-controlled, non-inferiority trial Device Name：Test Group: HCA-N Solution；Control Group: HTK Solution； Regulatory Classification：Class III Study Objective：To evaluate the safety and efficacy of HCA-N Solution for the preservation of donor kidneys in renal transplantation, through a comparative study with HTK Solution in kidney organ transplantation.

Indication for Use：This product is intended for flushing and preserving isolated kidneys for clinical renal transplantation.

Sample Size：250 subjects in total, with 125 subjects in each of the test and control groups.

Study Centers：Approximately 20 centers Primary Endpoint：(1)Percentage of subjects experiencing delayed graft function (DGF) post-transplantation. (2)DGF is defined as the need for dialysis within 1 week after transplantation.

Secondary Endpoints：(1)Percentage of subjects with eGFR > 30 mL/(min·1.73 m²) within 28 days post-transplantation;(2)Time to first eGFR > 30 mL/(min·1.73 m²) within 28 days post-transplantation;(3)Change in eGFR from baseline (the last value before transplantation) at Days 1, 3, 7, 14, and 28 post-transplantation;(4)Device deficiencies.

Safety Evaluation Indicators：Adverse events (AEs) and serious adverse events (SAEs) and their incidence rates;Vital signs, physical examination, laboratory test parameters, etc.

Inclusion Criteria (Both donor and recipient must meet their respective inclusion criteria for enrollment) Recipients must meet all of the following criteria 1-4:(1)Age 18 to 65 years (inclusive), regardless of gender;(2)Diagnosed as eligible for allogeneic renal transplantation and willing to undergo allogeneic renal transplantation;(3)Understand and agree to comply with the study requirements and voluntarily sign the informed consent form;(4)Require renal transplantation and be first-time transplant recipients.

Donors must meet all of the following criteria 5-6:(5)Donor kidney source aged 18 to 65 years (inclusive), regardless of gender;(6)Donor's last serum creatinine before kidney procurement < 2 mg/dL (177 μmol/L), and not having received hemodialysis.

Exclusion Criteria (Recipients meeting any of the following criteria 1-8 will be excluded):(1)Planned for dual kidney transplantation;(2)Planned for multi-organ combined transplantation;(3)History of previous organ transplantation;(4)Concurrent severe diseases, such as severe hepatic impairment, cardiopulmonary insufficiency, coagulation disorders, etc.;(5)Diagnosis of malignant tumor within 5 years prior to enrollment (except for adequately treated cervical carcinoma in situ, localized cutaneous squamous cell carcinoma, basal cell carcinoma, prostate cancer not requiring antitumor therapy, thyroid cancer, breast ductal carcinoma in situ, and urothelial carcinoma below T1 stage);(6)Panel reactive antibody (PRA) > 10%;(7)Pregnant or lactating women;(8)Participation in other drug or device clinical trials within 3 months prior to enrollment.

Donors meeting any of the following criteria will be excluded:(1)Donor has received renal replacement therapy (hemodialysis/CRRT) prior to screening;(2)Donor has infectious diseases unsuitable for transplantation.(3)Other requirements:ABO blood type incompatibility between donor and recipient;Donor kidney warm ischemia time > 10 min, or cold ischemia time > 24 h;Mechanical perfusion preservation required as assessed by the investigator;Other conditions that the investigator deems inappropriate for participation in this trial.

Study Procedures

Screening Period (V1, D-14 to D-1):

Screen potential kidney transplant donors and recipients for eligibility. Obtain signed informed consent. Collect recipient demographic information, medical history, treatment history, and current disease history. Collect blood type (ABO and Rh), immunological test results (PRA, donor/recipient crossmatch test, HLA typing). Complete screening assessments: vital signs, physical examination, complete blood count, urinalysis (if applicable, same below), blood biochemistry, coagulation function, transfusion-transmitted infection markers, pregnancy test (for women of childbearing potential only), 12-lead ECG, and chest CT or X-ray. (Except for vital signs and physical examination, results from tests performed within 7 days prior to screening are acceptable.) Record the subject's preoperative eGFR baseline value (last value before transplantation).

Surgery Day (V2, D0) Enrollment/randomization assignment; Record vital signs; Renal transplantation surgery; Kidney preservation; Observe device deficiencies; Record post-transplant dialysis events; Record adverse events and concomitant treatments. Follow-up Visit (V3, D1) Record vital signs; Laboratory tests: complete blood count, blood biochemistry, and urinalysis; Record eGFR on Day 1 post-transplantation; Record dialysis events post-transplantation; Record adverse events and concomitant treatments. Follow-up Visit (V4, D3) Record vital signs; Laboratory tests: complete blood count, blood biochemistry, and urinalysis; Record eGFR on Day 3 post-transplantation; Record dialysis events post-transplantation; Record adverse events and concomitant treatments. Follow-up Visit (V5, D7 ± 1) Record vital signs; Laboratory tests: complete blood count, blood biochemistry, and urinalysis; Record eGFR on Day 7 post-transplantation; Record dialysis events post-transplantation; Record adverse events and concomitant treatments. Follow-up Visit (V6, D14 ± 2) Record vital signs;

Laboratory tests: complete blood count, blood biochemistry, and urinalysis; Record eGFR on Day 14 post-transplantation; Record dialysis events post-transplantation; Record adverse events and concomitant treatments. Follow-up Visit (V7, D28 ± 3) Record vital signs and physical examination; Laboratory tests: complete blood count, blood biochemistry, and urinalysis; Coagulation function, pregnancy test (for women of childbearing potential only); 12-lead ECG; Chest CT or X-ray; Record eGFR on Day 28 post-transplantation; Record dialysis events post-transplantation; Record adverse events and concomitant treatments. Long-term Follow-up Record eGFR; Record graft survival status and patient survival information; Record device-related adverse events. Statistical Analysis Primary Endpoint: The primary endpoint is the percentage of subjects experiencing delayed graft function (DGF) post-transplantation. Chi-square test / corrected chi-square test / Fisher's exact test will be used for comparison between groups, and 95% confidence intervals will be calculated.

Secondary Endpoints:

Percentage of subjects with eGFR > 30 mL/(min·1.73 m²) within 28 days post-transplantation: Chi-square test / corrected chi-square test / Fisher's exact test will be used for comparison between test and control groups, and 95% confidence intervals will be calculated; Time to first eGFR > 30 mL/(min·1.73 m²) within 28 days post-transplantation: Kaplan-Meier method will be used to estimate median time, 25%/75% percentiles, and their 95% confidence intervals; Kaplan-Meier curves will be plotted; Changes in eGFR from baseline at Days 1, 3, 7, 14, and 28 post-transplantation: Descriptive analysis (sample size, mean, standard deviation) will be performed for each group; between-group comparisons will be made using t-test / rank-sum test.

Safety Analysis: To be performed based on the Safety Set (SS). The number of cases, number of subjects, and incidence rates of adverse events and serious adverse events will be calculated. Adverse events will be summarized by severity, SOC/PT, relationship to the study product, etc., in terms of number of events, number of subjects, and incidence rates. Detailed listings of adverse events will be provided. Physical examination, vital signs, 12-lead ECG, laboratory, and other test results will be summarized descriptively.