Albumin Replacement Therapy in Septic Shock: A Randomized Clinical Trial

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