The Albumin Replacement Therapy in Septic Shock (ARISS) trial, published in JAMA Network Open was designed to determine whether albumin replacement improves survival in patients with septic shock. The study was conducted on behalf of the SepNet Critical Care Trials Group and ARISS investigators.
Albumin is a natural colloid with physiological roles extending beyond maintenance of plasma oncotic pressure. It binds and transports endogenous and exogenous substances, exerts anti-inflammatory and antioxidant effects, and modulates nitric oxide metabolism. Despite these theoretical benefits, clinical evidence supporting albumin use in sepsis remains conflicting. Previous large trials such as SAFE demonstrated no overall mortality benefit in critically ill patients, although subgroup analyses suggested possible benefit in patients with sepsis. Similarly, the ALBIOS trial found no overall mortality difference but reported a potential survival advantage in patients with septic shock receiving albumin.
Based on these findings, the ARISS trial hypothesised that early administration of 20% albumin, initiated within 6–24 hours of septic shock onset and titrated to maintain serum albumin concentrations ≥3.0 g/dL for up to 28 days, would reduce 90-day all-cause mortality.
ARISS was conducted in 23 ICUs in Germany. Adult patients with septic shock were eligible if they had infection, required vasopressors to maintain a mean arterial pressure ≥65 mm Hg despite adequate fluid resuscitation, had serum lactate <18 mg/dL, and were within 24 hours of septic shock diagnosis.
Patients were randomised 1:1 to albumin therapy or standard care. The treatment group received a 60 g loading dose of 20% albumin within 6–24 hours of septic shock diagnosis, followed by daily dosing (40–80 g depending on measured serum albumin) to maintain concentrations ≥3.0 g/dL. Albumin could be administered for up to 28 days during ICU stay. The control group received standard care with crystalloids; albumin use was permitted if clinically indicated.
The primary endpoint was 90-day all-cause mortality. Secondary endpoints included 28- and 60-day mortality, ICU and in-hospital mortality, organ dysfunction assessed by Sequential Organ Failure Assessment (SOFA) score (excluding neurological component), ventilator- and vasopressor-free days, ICU and hospital length of stay, cumulative fluid balance, and adverse events (AEs). A total of 440 patients were enrolled (median age 69 years; 65.9% male), with 222 allocated to albumin and 218 to control.
Baseline characteristics were comparable between groups. The median Simplified Acute Physiology Score (SAPS II) was 54 in both groups. The median SOFA score was 11 in the albumin group and 10 in controls. The most common infection sources were abdominal (36.4%) and pulmonary (24.8%). Nearly half of the patients were admitted following emergency surgery. Median baseline serum albumin was 2.2 g/dL in both groups.
In the albumin group, median treatment duration was 5 days, with 15 patients receiving the full 28-day course. Despite protocolised dosing, more than half of patients failed to maintain albumin ≥3.0 g/dL throughout their ICU stay. Protocol deviations were frequent. Notably, 48.6% of control patients received albumin during their ICU stay, reflecting guideline-based allowance for early resuscitation.
Ninety-day mortality did not differ significantly between groups: 43.3% (91/210) in the albumin group versus 45.9% (96/209) in controls. Although 28-day mortality (31.0% vs 38.1%) and 60-day mortality (38.9% vs 45.2%) were numerically lower in the albumin group, these differences were not statistically significant.
ICU mortality (32.4% vs 34.8%) and in-hospital mortality (40.4% vs 44.8%) were also similar. There were no significant differences in ICU or hospital length of stay, ventilator-free days, vasopressor-free days, cumulative fluid balance, or total fluid administration.
SOFA scores, organ failure progression, haemodynamic parameters, and oxygenation indices were comparable between groups. Subgroup analyses stratified by lactate, SAPS II, SOFA, and APACHE II scores showed no survival benefit in any predefined subgroup. Per-protocol and modified per-protocol analyses confirmed the absence of significant mortality differences.
A total of 267 AEs occurred in 121 patients (54.5%) in the albumin group and 202 events in 105 patients (48.1%) in controls. The frequency and severity of AEs, including sepsis-related events, were similar between groups. No safety signal or excess harm was identified, supporting the safety profile of albumin under the trial protocol.
The ARISS trial demonstrated that albumin therapy, titrated to maintain serum concentrations ≥3.0 g/dL, did not improve 90-day survival in patients with septic shock. These findings do not support routine albumin replacement in this population.
Overall, in patients with septic shock, albumin replacement therapy targeting serum albumin ≥3.0 g/dL was safe but did not reduce 90-day mortality compared with standard care. Owing to premature trial termination and limited statistical power, uncertainty remains. Further adequately powered trials are required to clarify whether specific subgroups of septic shock patients may benefit from albumin therapy.
Source: JAMA
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