Evaluation of Human Albumin Solution on Acute Kidney Injury Incidence Post-Liver Transplantation

The primary objective of this study is to evaluate whether the administration of **albumin** to maintain serum concentrations above 30 g/L for five days reduces the incidence of acute kidney injury (AKI) by Day 7 following liver transplantation, compared to a control group receiving albumin only when serum levels fall to 20 g/L or below. This is clinically relevant as AKI is a common complication post-liver transplantation, impacting patient outcomes and healthcare resources.

Secondary objectives include assessing:

• Occurrence and severity stages of AKI during the first 7 days post-transplantation.
• Hospital length of stay.
• Occurrence of calcineurin inhibitor-induced neurotoxicity and withdrawal.
• Occurrence of postoperative infections, acute graft rejection, and early graft dysfunction.
• Duration of mechanical ventilation and reintubation rate.
• Intensive Care Unit (ICU) length of stay and readmission rate.
• All-cause mortality.
• Impact of albumin administration on lymphopenia, lymphocyte proliferation, apoptosis, mitochondrial function, immunosuppression, and inflammation post-surgery.

The clinical trial involves **participants** who have undergone **liver transplantation**. The study population includes both male and female patients aged 18 years and older. Participants are recipients of primary liver allografts from deceased donors, including those after cardiac death, and the transplantation involves a single organ, specifically the liver. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants must have the capability to understand the purpose and risks of the study and provide written informed consent. No specific lifestyle considerations such as diet or physical activity are mentioned as part of the trial criteria.

The clinical trial is designed to evaluate the impact of **human albumin solution** supplementation on kidney dysfunction following liver transplantation. This is a phase IV, randomized, double-blind, controlled trial. The primary objective is to determine if maintaining serum albumin concentration above 30 g/L for five days post-transplantation reduces the incidence of acute kidney injury (AKI) by day 7, compared to a control group with restrained albumin administration. The trial is expected to commence recruitment on December 1, 2024, and conclude by July 1, 2028.

Participants will be randomly assigned to either the treatment group, receiving albumin to maintain serum levels above 30 g/L, or the control group, receiving albumin only when levels fall to 20 g/L or below. The study will involve several key visits: an initial screening visit to confirm eligibility, followed by regular monitoring visits during the first seven days post-transplantation to assess kidney function and albumin levels. Additional follow-up visits will occur up to 28 days post-transplantation to monitor secondary endpoints, including hospital length of stay, postoperative complications, and overall mortality.

The expected duration of participant involvement is approximately 28 days, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. Inclusion criteria require participants to be male or female, aged 18 years or older, and recipients of a primary liver allograft from a deceased donor. Participants must be capable of understanding the study's purpose and risks and provide written informed consent. The primary endpoint is the occurrence of AKI within the first seven days post-transplantation, assessed using KDIGO criteria. Secondary endpoints include the severity of AKI, postoperative complications, and overall survival within the first 28 days.

The clinical trial involves the administration of **HUMAN ALBUMIN SOLUTION**, which is the experimental medication under investigation. This product is a **solution for infusion** and is derived from blood, classified as a structurally diverse substance. The primary active ingredient is human albumin, and the solution is intended to be administered intravenously. The objective of the trial is to maintain serum albumin concentrations above 30 g/L in the treated group for a period of five days, with the aim of reducing the incidence of acute kidney injury (AKI) by Day 7 following liver transplantation. The maximum treatment period for the administration of this solution is five days, and the dosing is adjusted to achieve the desired serum concentration levels. The trial does not specify a maximum daily or total dose amount, indicating that dosing is tailored to individual patient needs to maintain the target serum concentration.

In addition to the experimental treatment, the study includes a control group that receives albumin administration only when serum concentrations fall to 20 g/L or below. This comparator treatment serves as a standard-of-care reference to evaluate the efficacy of the experimental regimen. The trial does not involve any pediatric formulations, and the human albumin solution is not classified as an orphan drug. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol and to accurately assess the impact of the treatment on kidney function post-transplantation.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints related to the occurrence and severity of **Acute Kidney Injury (AKI)** following liver transplantation. The primary endpoint is the occurrence of AKI during the first 7 days post-transplantation, assessed using the KDIGO criteria. Secondary endpoints include the severity of each AKI episode within the same timeframe, hospital length of stay, postoperative complications such as Tacrolimus-induced neurotoxicity, and the occurrence of postoperative infections, all measured at Day 28. Additional secondary endpoints include acute graft rejection, early graft dysfunction, duration of mechanical ventilation, reintubation, and Intensive Care Unit (ICU) length of stay, as well as ICU readmission and mortality within the first 28 days post-surgery.

These efficacy parameters will be collected and analyzed using standardized clinical criteria and laboratory tests. The KDIGO criteria will be employed to assess AKI, while other endpoints will be evaluated using a combination of clinical observations, laboratory measurements, and patient records. The trial will also utilize specific tools such as flow cytometry and the Seahorse analyzer for assessing immune function and mitochondrial respiration, respectively. The study will monitor plasmatic levels of IL-6 and other biomarkers to provide additional insights into the physiological responses post-transplantation. Data collection will occur at specified timepoints, including Day 7 and Day 28, to ensure comprehensive assessment of the treatment's efficacy over the course of the trial.