A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis

N Engl J Med. 2021 Mar 4;384(9):808-817. doi: 10.1056/NEJMoa2022166.

Abstract

Background: Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level of 30 g per liter or greater in these patients with repeated daily infusions of 20% human albumin solution, as compared with standard care, would reduce the incidences of infection, kidney dysfunction, and death is unknown.

Methods: We conducted a randomized, multicenter, open-label, parallel-group trial involving hospitalized patients with decompensated cirrhosis who had a serum albumin level of less than 30 g per liter at enrollment. Patients were randomly assigned to receive either targeted 20% human albumin solution for up to 14 days or until discharge, whichever came first, or standard care. Treatment commenced within 3 days after admission. The composite primary end point was new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment.

Results: A total of 777 patients underwent randomization, and alcohol was reported to be a cause of cirrhosis in most of these patients. A median total infusion of albumin of 200 g (interquartile range, 140 to 280) per patient was administered to the targeted albumin group (increasing the albumin level to ≥30 g per liter), as compared with a median of 20 g (interquartile range, 0 to 120) per patient administered to the standard-care group (adjusted mean difference, 143 g; 95% confidence interval [CI], 127 to 158.2). The percentage of patients with a primary end-point event did not differ significantly between the targeted albumin group (113 of 380 patients [29.7%]) and the standard-care group (120 of 397 patients [30.2%]) (adjusted odds ratio, 0.98; 95% CI, 0.71 to 1.33; P = 0.87). A time-to-event analysis in which data were censored at the time of discharge or at day 15 also showed no significant between-group difference (hazard ratio, 1.04; 95% CI, 0.81 to 1.35). More severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group.

Conclusions: In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target of 30 g per liter or more was not more beneficial than the current standard care in the United Kingdom. (Funded by the Health Innovation Challenge Fund; ATTIRE EudraCT number, 2014-002300-24; ISRCT number, N14174793.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albumins / administration & dosage
  • Albumins / adverse effects
  • Albumins / therapeutic use*
  • Ascites / etiology
  • Ascites / therapy
  • Female
  • Hospitalization
  • Humans
  • Infusions, Intravenous
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / therapy*
  • Liver Cirrhosis, Alcoholic / blood
  • Liver Cirrhosis, Alcoholic / therapy
  • Male
  • Middle Aged
  • Pulmonary Edema / etiology
  • Serum Albumin*
  • Treatment Failure

Substances

  • Albumins
  • Serum Albumin

Associated data

  • EudraCT/2014-002300-24
  • ISRCTN/14174793