Biomarker‑Guided Personalized Human Serum Albumin Therapy in Decompensated Cirrhosis with Ascites: A Multinational Randomized Controlled Trial

The primary objective of the ALB-TRIAL is to validate the predictive **biomarker** of treatment response to human albumin therapy in patients with **liver cirrhosis** and ascites. This objective is clinically relevant as it aims to enhance the personalized treatment approach for individuals suffering from decompensated cirrhosis, potentially improving therapeutic outcomes and patient management. The study evaluates the efficacy of human albumin, administered as a solution for infusion, in predicting treatment response, which could lead to more targeted and effective interventions for this patient population.

The clinical trial involves a total of **30 participants** diagnosed with **liver cirrhosis**. The study population includes both male and female subjects, aged 18 years and older, who have been diagnosed with decompensated liver cirrhosis, as defined by a Child-Pugh score of 7-12, and have clinical and/or ultrasound evidence of ascites. Participants were selected based on specific inclusion criteria, including the requirement that at least five days have passed since the resolution of a decompensation event or any condition necessitating hospitalization. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The study population is considered vulnerable, indicating that additional ethical considerations are in place to protect the participants. The trial aims to validate the predictive biomarker of treatment response to human albumin therapy in this patient group.

The clinical trial is designed to evaluate the efficacy of **human serum albumin** therapy in patients with **liver cirrhosis** and ascites. This study is a randomized, double-blind, controlled trial involving two groups: one receiving Human Albumin Grifols 200 g/l solution for infusion and the other receiving Salina Fisiológica Grifols 0.9% solution for infusion as a placebo. The trial aims to validate a predictive biomarker for treatment response, with primary endpoints focusing on the cumulative number of liver-related clinical outcomes, including variceal bleeding, ascites, and spontaneous bacterial peritonitis. Secondary endpoints include 6-month survival, quality of life, and the incidence of various liver-related complications.

The trial is expected to last until March 31, 2025, with participant recruitment having commenced on January 1, 2023. Participants will be involved in the study for a maximum treatment period of 26 weeks. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as a Child-Pugh score of 7-12 and evidence of ascites, followed by regular follow-up visits to monitor treatment response and adverse events. The end-of-study visit will assess the overall outcomes and any long-term effects of the treatment.

Participants may be withdrawn from the study if they experience severe adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial is conducted under strict ethical guidelines, ensuring that all procedures are in line with regulatory standards for clinical research. The study's design and methodology are structured to provide robust data on the effectiveness and safety of human serum albumin in managing complications associated with liver cirrhosis.

The clinical trial involves the administration of **Human Albumin Grifols 200 g/l**, a **solution for infusion**. This experimental medication contains **human serum albumin** as the active substance, which is a structurally diverse substance derived from blood. The pharmaceutical form is a solution intended for intravenous infusion. The maximum daily dose is 500 ml, with a total maximum dose of 500 ml over a treatment period of up to 26 weeks. The administration is conducted via intravenous infusion, and the product is manufactured by Instituto Grifols, S.A. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, the study utilizes **Salina Fisiológica Grifols 0.9%**, a **solution for infusion** containing **sodium chloride** as the active substance. This non-experimental treatment serves as a comparator and is also administered via intravenous infusion. The maximum daily and total dose for this solution is 500 ml, matching the treatment period of up to 26 weeks. The sodium chloride solution is a chemically derived substance, produced by Laboratorios Grifols, S.A. Participant compliance with the administration schedule is similarly monitored to maintain the integrity of the trial data.

Efficacy in the clinical trial titled "ALB-TRIAL: Personalized Long-term Human Albumin Treatment in Patients With Decompensated Cirrhosis and Ascites" will be assessed using a combination of primary and secondary endpoints. The primary endpoint focuses on the cumulative number of liver-related clinical outcomes, including variceal bleeding, ascites, spontaneous bacterial peritonitis, infections requiring hospitalization, acute kidney injury, and overt hepatic encephalopathy, with death, liver transplantation, and TIPS as counting and censoring events.

Secondary endpoints include a range of clinical and patient-reported outcomes: 6-month survival, the number of episodes of acute-on-chronic liver failures, number of organ failures, time-to-first liver-related clinical outcome, patients' quality of life, time to first hospital admission, number of hospital admissions, days spent on hospitalization, number of intensive care unit admissions, length of intensive care unit admissions, number of large volume paracentesis, analysis of the cost/effectiveness ratio, health economic evaluation, changes in serum albumin levels, number of treatment-related adverse events, number of treatment-related serious adverse events, signatures associated with a poor prognosis as defined by the Microb-Predict biomarker, and incidences of refractory ascites, variceal bleeding, spontaneous bacterial peritonitis, infection requiring hospitalization, acute kidney injury, hepatorenal syndrome acute kidney injury, overt hepatic encephalopathy, liver transplantation, and TIPS insertion.