Safety and efficacy of a high quality human albumin solution in patients with decompensated cirrhosis (SUPERalbumin)

Liver cirrhosis represents a major health-care problem due to the high mortality rate, being the 8th leading cause of death in Europe, and to the elevated direct and indirect social costs.
Human albumin (HA) is the most abundant circulating protein and is provided of both oncotic and non-oncotic properties. In patients with decompensated cirrhosis, besides the onset of hypoalbuminemia, structural and functional damages accumulate in the molecule that parallel the severity of the disease. Thus, HA administration aims at restoring physiological functions that can counteract major pathophysiological drivers of the disease, such as circulatory dysfunction, systemic inflammation and oxidative stress, and immune dysfunction.
HA infusion is one of the most frequent therapeutic interventions in patients with decompensated cirrhosis.
However, randomized clinical trials (RCTs) assessing HA administration have so far produced controversial results, so that HA appears to be partially effective or even ineffective in many patients with decompensated cirrhosis. The cause of these variant findings is not clear and likely multifactorial.
A possible explanation could be searched in the low quality of the commercial HA, which presents a significant structural damage and functional dysfunction of the molecule, likely leading to a partial loss of the therapeutic efficacy.
Our hypothesis is that a high-quality HA (hq-HA) solution with enriched oncotic properties (SUPERalbumin), together with their transferability in clinical practice, is an attractive option to overcome the above-described shortcomings, which could limit the effectiveness of the standard commercial solutions.
In previous experimental research, we unveiled that, while the manufacturing process has no major impact, relevant structural alterations accumulate during the shelf-life of commercial HA at room temperature. We then developed a high- quality HA solution by combining two different approaches: first, an almost complete reversion of the oxidation that occurs at the main binding site of the molecule (Cys-34) was achieved by adding pharmaceutical grade glutathione (GSH); second, the structural damage of other molecular sites was largely prevented by storing HA vials at 4°C.
Taken together, these results support the possibility of producing, with marginal additional costs, an easy-to use hq-HA solution by adding GSH, at the bed of the patient 10 minutes before infusion, to the current commercial HA vials stored 4°C during shelf-life.
This proposal consists of a proof-of-concept phase 2 RCT including 80 patients (1:1) with cirrhosis and ascites and aiming to demonstrate the safety and efficacy of this hqHA solution as compared to the standard commercial HA solution in patients with decompensated cirrhosis and ascites. Besides safety, the evidence of efficacy will be assessed by a series of clinical end-points, as well as by exploratory end-points related to the main pathophysiological mechanisms of decompensated cirrhosis.
This clinical study will provide several critical information. If the results will prove their safety and show signals of a greater efficacy, we are confident that this newly developed hqHA formulation will open a new direction towards a more appropriate use of HA in decompensated cirrhosis, particularly in patients with a more severe illness where systemic inflammation is prominent, leading to an improvement of clinical outcomes and a reduction of healthcare costs.