TOPLINE:

In a multicenter randomized clinical trial of 440 patients with septic shock, albumin replacement therapy targeting serum levels ≥ 3.0 g/dL did not reduce 90-day mortality compared with standard crystalloid therapy. Albumin was safe; however, the trial ended early, leaving results inconclusive.

METHODOLOGY:

• Researchers conducted a prospective, multicenter, open-label randomized clinical trial across 23 ICUs in Germany and enrolled 440 adult patients (median age, 69 years; 65.9% men) within 24 hours of septic shock onset between 2019 and 2022.
• Patients were randomly assigned to receive either a 60-g loading dose of 20% human albumin, followed by dosing to maintain serum albumin levels ≥ 3.0 g/dL for up to 28 days during ICU admission (n = 222), or standard fluid administration with crystalloids (n = 218). All patients received standard ICU care and were followed up for 90 days.
• The primary outcome was the 90-day all-cause mortality rate, and secondary outcomes were 28-day and 60-day mortality rates, ICU and hospital mortality rates, organ dysfunction (assessed using the Sequential Organ Failure Assessment score), length of stay, ventilator-free and vasopressor-free days, fluid administration volumes, and adverse events.
• The study was terminated prematurely due to low enrollment rates during COVID. The primary outcome was available for analysis in 210 patients in the albumin group and 209 patients in the control group.

TAKEAWAY:

• The rates of 90-day mortality did not differ significantly between the albumin group and the control group (43.3% vs 45.9%; relative risk [RR], 0.94; P = .71).
• The rates of 28-day mortality (31.0% vs 38.1%; RR, 0.81) and 60-day mortality (38.9% vs 45.2%; RR, 0.86) were lower in the albumin group than in the control group, but the differences were not statistically significant.
• ICU and hospital mortality rates were similar between the groups, with no significant differences in median ICU length of stay, hospital length of stay, vasopressor-free days, or ventilator-free days.
• Adverse events occurred in 54.5% of patients in the albumin group and 48.1% of patients in the control group, with similar frequencies and severities of both sepsis-related and non-sepsis-related events between the groups.

IN PRACTICE:

"In this randomized clinical trial study of patients with septic shock, albumin administration aiming to maintain serum albumin concentrations greater than 3.0 g/dL was safe but did not improve 90-day survival in these patients," the authors wrote.

"Uncertainty remains due to premature termination of the study, and additional studies are recommended," they added.

SOURCE:

The study was led by Yasser Sakr, MD, Jena University Hospital, Jena, Germany. It was published online on February 19, 2026, in JAMA Network Open.

LIMITATIONS:

Premature termination of the trial due to low enrollment rates during the COVID pandemic left the study underpowered to detect potential benefits of albumin replacement therapy. Target serum albumin concentrations > 3.0 g/dL were not achieved in over half of the patients, likely due to high illness severity and pronounced dilutional effects from large fluid resuscitation volumes. The control group's use of albumin, permitted under current guidelines when excessive crystalloid fluid is required for hemodynamic stabilization, may have reduced separation between the treatment groups; however, this use was primarily limited to the early resuscitation phase rather than the sustained replacement strategy tested in the trial. Additionally, the predominantly postoperative patient population may have limited generalizability, as surgical factors beyond sepsis management could have affected outcomes.

DISCLOSURES:

This study was funded by Deutsche Forschungsgemeinschaft and Grifols. One author disclosed receiving grants from Biotest, CytoSorbents, Daiichi Sankyo, and Fresenius Medical Care and personal fees from ADVITOS, CSL Behring, Fresenius Medical Care, Gilead Sciences, MSD, Pfizer, Shionogi, Zoll, and AstraZeneca outside the submitted work. Another author disclosed receiving personal fees from CSL Behring.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.