The Effectiveness and Safety of Hypertonic Citrate Adenine-New (HCA-N) Solution for the Preservation of Kidney Grafts During Kidney Transplantation

This is a multicenter, randomized, double-blind, positive-controlled, non-inferiority clinical trial evaluating HCA-N Solution versus Histidine-Tryptophan-Ketoglutarate (HTK) Solution for the preservation of donor kidneys in renal transplantation. HCA-N Solution is a Class III device intended for flushing and preserving isolated kidneys for clinical renal transplantation. Approximately 250 subjects will be enrolled, with 125 subjects in the test group and 125 in the control group, across approximately 20 centers. Donor-recipient pairs must meet the protocol-defined eligibility criteria; eligibility details are provided in the Eligibility Criteria section, and randomization will be 1:1 to the test or control group.

During the screening period (Visit 1 [V1], Day -14 to Day -1 [D-14 to D-1]), potential donors and recipients will be screened for eligibility, informed consent will be obtained, and baseline demographic, medical, immunological, and laboratory information will be collected. The recipient's preoperative baseline estimated glomerular filtration rate (eGFR) value, defined as the last value before transplantation, will be recorded.

On surgery day (Visit 2 [V2], Day 0 [D0]), enrollment and randomization will occur. Vital signs will be recorded, renal transplantation surgery will be performed, and the donor kidney will be flushed and preserved using the assigned preservation solution. Device deficiencies, post-transplant dialysis events, adverse events (AEs), and concomitant treatments will be recorded.

Follow-up visits will occur at Visit 3 (V3, Day 1 [D1]), Visit 4 (V4, Day 3 [D3]), Visit 5 (V5, Day 7 [D7] ± 1), Visit 6 (V6, Day 14 [D14] ± 2), and Visit 7 (V7, Day 28 [D28] ± 3). At these visits, vital signs, laboratory tests including complete blood count, blood biochemistry, and urinalysis, eGFR, dialysis events, adverse events, and concomitant treatments will be recorded. The Day 28 visit will also include physical examination, coagulation function, pregnancy testing for women of childbearing potential, 12-lead electrocardiogram (ECG), and chest computed tomography (CT) or X-ray. Long-term follow-up will collect eGFR, graft survival status, patient survival information, and device-related adverse events.

Efficacy will be assessed primarily by the occurrence of delayed graft function (DGF) after transplantation, with additional renal function parameters within 28 days post-transplantation as specified in the Outcome Measures section. Safety will be evaluated through AEs, serious adverse events (SAEs), vital signs, physical examination, laboratory parameters, ECG, and other protocol-specified assessments.

Statistical analysis will be performed according to prespecified analysis sets. For the primary endpoint, between-group comparisons will use chi-square test, corrected chi-square test, or Fisher's exact test as appropriate, with 95% confidence intervals calculated. Binary secondary endpoints will be analyzed using similar categorical methods. Time-to-event endpoints will be analyzed using the Kaplan-Meier method, including median time, 25%/75% percentiles, 95% confidence intervals, and Kaplan-Meier curves. Continuous eGFR changes from baseline at Days 1, 3, 7, 14, and 28 post-transplantation will be summarized descriptively by group and compared using t-test or rank-sum test as appropriate. Safety analyses will be based on the Safety Set (SS) and will summarize AEs and SAEs by number of events, number of subjects, and incidence rates; AEs will be summarized by severity, System Organ Class (SOC)/Preferred Term (PT), and relationship to the study product. Physical examination, vital signs, 12-lead ECG, and laboratory results will be summarized descriptively.

Inclusion criteria

Recipients must meet all of the following criteria:

• Age 18 to 65 years (inclusive), regardless of gender.
• Diagnosed as eligible for allogeneic renal transplantation and willing to undergo allogeneic renal transplantation.
• Understand and agree to comply with the study requirements and voluntarily sign the informed consent form.
• Require renal transplantation and be first-time transplant recipients.

Donors must meet all of the following criteria:

• Donor kidney source aged 18 to 65 years (inclusive), regardless of gender.
• 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 will be excluded:

• Planned for dual kidney transplantation.
• Planned for multi-organ combined transplantation.
• History of previous organ transplantation.
• Concurrent severe diseases, such as severe hepatic impairment, cardiopulmonary insufficiency, coagulation disorders, etc.
• 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).
• Panel reactive antibody (PRA) > 10%.
• Pregnant or lactating women.
• Participation in other drug or device clinical trials within 3 months prior to enrollment.
• Donors meeting any of the following criteria will be excluded:
• Donor has received renal replacement therapy (hemodialysis or continuous renal replacement therapy [CRRT]) prior to screening.
• Donor has infectious diseases unsuitable for transplantation.

Other requirements:

• ABO blood group system incompatibility between donor and recipient.
• Donor kidney warm ischemia time > 10 minutes, or cold ischemia time > 24 hours.
• Mechanical perfusion preservation required as assessed by the investigator.
• Other conditions that the investigator deems inappropriate for participation in this trial.