Does long-term albumin therapy prolong survival in cirrhotic patients?

Long-term human albumin (LTA) therapy among cirrhotic patients with existing or prior ascites and acute decompensation results in improved transplant-free survival (TFS), mortality, and disease-related complications, according to the results of the PRECIOSA trial.

However, the hypothesized primary endpoint of 1-year TFS assessed in the intent-to treat population is not met when compared with standard medical therapy (SMT) alone.

Treatment with LTA had a hazard ratio (HR) of 0.80 (95 percent confidence interval [CI], 0.58‒1.10; p=0.17) at 1 year. This failed to meet the hypothesized HR of 0.6 (2-sided α of 5 percent) for LTA relative to SMT alone, reported principal investigator Dr Javier Fernández of the Hospital Clínic de Barcelona in Barcelona, Spain. [EASL 2025, abstract LBO-003]

Fernández and his team conducted PRECIOSA, a phase III, randomized, active-controlled, parallel-group, open-label trial in 14 countries across North America and Europe. A total of 410 patients were randomly allocated to SMT plus albumin (1.5 g/kg body weight, maximum 100 g, every 10 days for up to 12 months; treatment group; n=203) or SMT alone (control group; n=207).

Apart from 1-year TFS assessed in the intent-to-treat population, other outcomes assessed included 1-year mortality, 3- and 6-month TFS and mortality, as well as the incidence of disease-related complications. For safety, the research team assessed treatment-emergent serious adverse events (TESAEs) and suspected adverse drug reactions (SADRs).

The two treatment groups had similar demographic and baseline characteristics, with alcohol being the dominant aetiology for cirrhosis in both arms.

Treatment with LTA increased and maintained higher serum albumin concentrations in the treatment group, from 0.5 to 0.65 g/dL on average, compared with the control group.

TFS and mortality

Clinically meaningful improvements in the outcomes were observed at 3 (TFS: HR, 0.58, 95 percent CI, 0.34‒0.99; p=0.044; mortality: HR, 0.65, 95 percent CI, 0.37‒1.17; p=0.15) and 6 months (TFS: HR, 0.73, 95 percent CI, 0.50‒1.08; p=0.11; mortality: HR, 0.68, 95 percent CI, 0.44‒1.05; p=0.08) and at 1 year (TFS: HR, 0.80, 95 percent CI, 0.58‒1.10; p=0.17; mortality: HR, 0.77, 95 percent CI, 0.53‒1.10; p=0.15).

Unfortunately, the assumed HR at 1 year was not achieved with long-term LTA.

In terms of safety, the profile of LTA administration was acceptable. The treatment group showed fewer TESAEs than the control group (77 in 52 patients vs 127 in 70 patients), while SADRs were scarce (20 in 14 patients). No new adverse reactions attributed to LTA were seen.

“The LTA dosing regimen showed favourable safety and tolerability profile with no new adverse reaction risks beyond that on label … to limit adoption of the therapy,” Fernández said.

Previous studies, such as ANSWER, reported improvements in overall survival (OS) with LTA administration in patients with decompensated cirrhosis. [Lancet 2018;391:2417-2429]

PRECIOSA, on the other hand, focused on TFS and not just OS. Furthermore, the albumin concentration at baseline was much lower in ANSWER patients, according to Fernández. [https://www.medpagetoday.com/meetingcoverage/easl/115547]