Original Investigation 

Critical Care Medicine

Albumin Replacement Therapy in Septic Shock: A Randomized Clinical Trial

Yasser Sakr, Axel Nierhaus, Ulrike Schumacher, et al

JAMA Netw Open 2026;9;(2):e2559297. doi:10.1001/jamanetworkopen.2025.59297

Key Points

Question  Can the reported potential mortality reduction by albumin replacement in septic shock be confirmed in a randomized clinical trial?

Findings  In a multicenter randomized clinical trial, 440 adults with septic shock were treated with albumin therapy aiming to maintain serum albumin concentrations greater than 3.0 g/dL or with standard fluid therapy. Ninety-day mortality did not differ significantly between the albumin group (43.3%) and the controls (45.9%).

Meaning  These results suggest that albumin administration was safe but did not improve 90-day survival in patients with septic shock; results remain inconclusive due to premature trial termination.

Abstract

Importance  Albumin supplementation may reduce mortality in patients with septic shock; however, data from randomized clinical trials are limited.

Objective  To assess the impact of albumin administration on outcomes in patients with septic shock.

Design, Setting, and Participants  This multicenter, open-label randomized clinical trial was conducted between October 21, 2019, and May 2, 2022. Patients from 23 intensive care units in Germany enrolled within 24 hours of the onset of septic shock were followed up for outcome data up to 90 days. The statistical trial report was completed and filed with the federal authorities in December 2023; additional analyses were completed in October 2024. The study was terminated prematurely due to low enrollment rates.

Interventions  Protocol group patients received 20% albumin to maintain serum albumin levels of at least 3.0 g/dL for up to 28 days during their intensive care unit admission. The control group received standard fluid administration with crystalloids.

Main Outcomes and Measures  The primary end point was 90-day mortality; secondary end points included 28-day, 60-day, intensive care unit and in-hospital mortality, organ dysfunction or failure, total amount of fluid administration and total fluid balance while in the intensive care unit, duration of intensive care and hospital stays, and frequency of adverse events.

Results  Of 440 randomized patients (median [IQR] age, 69 [59-78] years; 290 [65.9%] male), 222 received albumin and 218 received standard fluids. Baseline characteristics were comparable. Ninety-day mortality was 43.3% (91 of 210) in the albumin group vs 45.9% (96 of 209) in controls (relative risk, 0.94; 95% CI, 0.76-1.17; P = .71). No significant differences were observed for secondary end points.

Conclusions and Relevance  In this randomized clinical trial of patients with septic shock, albumin administration was safe but did not improve 90-day survival. As this trial was prematurely terminated, results remain inconclusive and additional studies are recommended.

Trial Registration  ClinicalTrials.gov Identifier: NCT03869385