Multicenter, randomized, double-blind trial comparing albumin and polygeline for intravascular fluid loading in patients with cirrhosis and tense ascites treated with paracentesis

Objectives

Patients with cirrhosis and tense ascites treated with paracentesis require repeated intravascular fluid loading with colloid solutions. In such patients, human albumin was suggested to be superior to a synthetic colloid for fluid loading, albeit at a higher cost. Thus, we started a 6-month trial aimed to compare the outcomes in patients with cirrhosis who were treated with albumin with the outcomes in those treated with bovine-derived polygeline. We also aimed to investigate hospital costs. This trial had to be prematurely interrupted due to theoretical concern regarding safety of bovine-derived products.

Methods

A multicenter, randomized, double-blind trial was conducted in patients with tense ascites who were randomly assigned to receive intravenously either 20% human albumin or polygeline. The prespecified primary end point was the time to a first liver-related event (a composite of death, episodes of recurrent tense ascites, renal impairment, hyponatremia, bacterial infection, encephalopathy, portal hypertensive bleeding, the occurrence of hepatocellular carcinoma, liver transplantation) during the in-trial period (i.e. the period during which patients had only received the assigned colloid). All events were blindly adjudicated.

Results

Thirty patients were assigned to albumin and 38 to polygeline. At baseline, all patients had therapeutic paracentesis. The duration of the in-trial period was higher in the albumin group than in the polygeline group (mean [± SD], 121 ± 64 days vs 77 ± 58 days; P = 0.004) due to lower frequencies of unblinded colloid infusions and of dropout in patients assigned to albumin. There were 24 liver-related first events in the albumin group (58.9 per 100 person-months) and 34 liver-related first events in the polygeline group (107.4 per 100 person-months; the hazard ratio for a first liver-related event with albumin therapy was 0.51 [95% confidence interval, 0.30–0.88];P = 0.016). The median time for the first event was higher in the albumin group than in the polygeline group (20 days [95% confidence interval, 11–46 days] vs 7 days [95% confidence interval, 6–13 days]; P = 0.044). The median total hospital cost was lower in the albumin group than in the polygeline group (€1915 for a 30-day period vs €4612 for a 30-day period, respectively; P = 0.004).

Conclusion

In patients with cirrhosis and tense ascites treated with paracentesis, human albumin is more effective than polygeline to prevent the occurrence of any first event related to liver disease. This beneficial effect seems to be associated with a decrease in hospitalization-related cost.