ALB-TRIAL: Personalized Long-term Human Albumin Treatment in Patients With Decompensated Cirrhosis and Ascites

The primary objective of the study is to validate the predictive **biomarker** of treatment response to human albumin therapy in patients with **liver cirrhosis** and ascites. This is clinically relevant as it aims to enhance the personalized treatment approach, potentially improving patient outcomes by identifying those who are most likely to benefit from human albumin therapy. The study involves the administration of Human Albumin Grifols 200 g/l, a solution for infusion, and compares its effects with a placebo, specifically Salina Fisiológica Grifols 0.9% solution for infusion, which contains sodium chloride. The trial seeks to provide insights into the efficacy of human albumin in managing complications associated with decompensated cirrhosis, thereby contributing to the optimization of therapeutic strategies for this patient population.

The clinical trial involves a total of **60 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 population is considered vulnerable, and the selection process ensures a representative sample of individuals with the condition under investigation. Lifestyle factors such as diet and physical activity are not specified in the available data.

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 with a duration of 26 weeks. Participants will be randomly assigned to receive either the investigational product, Human Albumin Grifols 200 g/l, or a placebo, Salina Fisiológica Grifols 0.9% solution, both administered via intravenous infusion. The trial aims to validate a predictive biomarker for treatment response, with primary endpoints including the cumulative number of liver-related clinical outcomes, such as variceal bleeding and spontaneous bacterial peritonitis, with death, liver transplantation, and TIPS as counting and censoring events.

The trial will commence with a screening visit to confirm eligibility based on criteria such as a Child-Pugh score of 7-12, evidence of ascites, and age of 18 years or older. Participants must have resolved any decompensation event or hospitalization condition at least five days prior to enrollment. Following the screening, participants will undergo regular follow-up visits to monitor treatment response and safety, with assessments including serum albumin levels, quality of life, and incidence of adverse events. The end-of-study visit will conclude the trial, evaluating the primary and secondary endpoints, including 6-month survival and the number of acute-on-chronic liver failure episodes.

Participant involvement is expected to last for the full 26-week treatment period unless early termination is warranted. Conditions for early termination include the occurrence of serious adverse events, withdrawal of consent, or any medical condition that contraindicates continued participation. The trial is set to end by September 2024, with recruitment having started in September 2022. The study is not classified as a low-intervention trial, as it involves the administration of authorized medicinal products in a clinical setting.

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 for infusion, and it is administered via **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 product is manufactured by Instituto Grifols, S.A., and is not a pediatric formulation. The trial aims to validate the predictive biomarker of treatment response in patients with decompensated cirrhosis and ascites.

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, with a treatment period of up to 26 weeks. The product is manufactured by Laboratorios Grifols, S.A., and is classified as a chemical substance. This comparator treatment is used to assess the efficacy and safety of the experimental medication in the clinical trial.

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 range 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 variety of measures such as 6-month survival, the number of episodes of acute-on-chronic liver failures, number of organ failures, time-to-first liver-related clinical outcome, and patients' quality of life. Additional secondary endpoints involve time to first hospital admission, number of hospital admissions, days spent on hospitalization, number of intensive care unit admissions, and length of intensive care unit admissions. The trial will also evaluate the number of large volume paracentesis, analysis of the cost/effectiveness ratio, health economic evaluation, changes in serum albumin levels, and the number of treatment-related adverse and serious adverse events.

Furthermore, the trial will assess signatures associated with a poor prognosis as defined by the Microb-Predict biomarker, incidence of refractory ascites, variceal bleeding, spontaneous bacterial peritonitis, infections requiring hospitalization, acute kidney injury, hepatorenal syndrome acute kidney injury, overt hepatic encephalopathy, liver transplantation, and TIPS insertion. These endpoints will be measured and analyzed throughout the trial duration to determine the efficacy of the treatment.