Clinical trial NCT05148286: Albumin and Crystalloid Administration in Septic Shock
Official title: Albumin and Crystalloid Administration in Septic Shock (ALCAMIST): Multi-center, Open Labelled Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Septic Shock
Keywords: Septic shock
Fluid resuscitation
Albumin
Crystalloid
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Samsung Medical Center
name: Gangnam Severance Hospital
name: Chungnam National University Hospital
name: Seoul National University Hospital
name: Seoul National University Bundang Hospital
name: SMG-SNU Boramae Medical Center
name: Hanyang University
name: Korea University Ansan Hospital
First posted: 2021-12-08
Enrollment: 2426
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The current guideline emphasizes fluid resuscitation as the mainstay of initial management for septic shock. Albumin has the oncotic activity to maintain intravascular volumes with additional beneficial properties in sepsis. Prior studies showed that the replacement of albumin might have survival advantages in patients with septic shock. The investigators aim to assess whether the early administration of albumin with crystalloid as initial fluid resuscitation improves survival in patients with septic shock compared to resuscitation without albumin.

Detailed description: Sepsis is a leading cause of mortality worldwide, contributing to an estimated 11 million deaths in 2017-or 20% of all global deaths. Due to recent advances in the medical management and treatment of sepsis, the mortality of sepsis has been declined in these years, but still stayed at a high level. From 2004, the Surviving Sepsis Campaign (SSC) suggested a protocolized bundle therapy to facilitate implementation at the bedside with a defined target. Recent guideline states that this resuscitation bundle treatment should be initiated within 1 h of the emergency department (ED) triage time, named as 1-h bundle.

Fluid resuscitation, which is the mainstay of treatment to restore a patient's tissue perfusion, is associated with outcome in emergency department patients. The current guideline recommends that crystalloid for initial fluid resuscitation in sepsis and albumin can be additionally administered when patients require substantial amounts of crystalloid. Besides its oncotic functions to provide adequate intravascular volume, albumin has several beneficial properties for sepsis patients, including binding and transport of various endogenous molecules, anti-inflammatory and anti-oxidative effects, and modulation of nitric oxide metabolism. In 2004, a large randomized, prospective, double-blind study was performed in 7000 critically ill patients (SAFE study) to evaluate the effect of volume replacement therapy with human albumin on the outcome compared to only crystalloid. Although the survival rates were similar between the groups, a post hoc analysis of 1218 patients with severe sepsis showed improved survival in the albumin group compared to crystalloid alone. Furthermore, the ALBumin Italian Outcome Sepsis (ALBIOS) study investigated the effect of albumin administration and maintenance of serum albumin concentrations to at least 30 g/l on outcome in patients with severe sepsis and septic shock. This study showed a similar result to SAFE study that no difference on the outcome between the groups. Nevertheless, in the 1121 patients with septic shock, 90-day mortality was lower in the albumin group (564 patients) than in the non-albumin group (43.6 vs. 49%, p = 0.03). Recently, a retrospective study which evaluated the effect of administration of albumin combined with crystalloids in septic patients showed improved survival in 28 days. Therefore, accumulating evidence suggests that early albumin administration may provide a survival benefit in patients with severe and advanced sepsis. However, no prospective, randomized trial has adequately studied this hypothesis in patients with septic shock.

The aim of the ALCAMIST (ALbumin and Crystalloid AdMinistration In SepTic shock) study is to investigate the effect of albumin and crystalloid administration as an initial fluid choice in septic shock compared to crystalloid alone on patient survival.

Eligibility criteria: Inclusion Criteria:

* Adult patients (≥ 18 years) who visit an ED directly and are suspected of sepsis with shock
* Shock is defined as hypotension (mean arterial blood pressure (MAP) \< 65 or systolic blood pressure \< 80) and tissue hypoperfusion such as an initial serum lactate level ≥ 4 mmol/dL.

Exclusion Criteria:

* patients who are transferred from another hospital after initial fluid administration
* patients who have set limitations on treatment (e.g. patients with a signed do-not-resuscitate order)
* patients with moribund conditions with life expectancy less than 28 days due to secondary diseases or advanced malignant disease and palliative situations with life expectancy less than 6 months
* patients who have been administered albumin before enrollment
* patients who have known hypersensitivity to albumin
* Clinical conditions, where albumin administration may be unfavorable (e.g. pulmonary edema, congestive heart failure, traumatic brain injury)
* lactation
* patients who do not voluntarily consent to participate in the trial.

Primary outcomes:
measure: 28-day all-cause mortality
timeFrame: 28-days
Secondary outcomes:
measure: 90-day all-cause mortality
timeFrame: 90 days
measure: ICU mortality
timeFrame: 28 days
measure: Hospital mortality
timeFrame: 28 days
measure: The Sequential organ Failure Assessment (SOFA) score
timeFrame: 28 days
measure: Intensive Care Unit (ICU) stay
timeFrame: 90 days
measure: 7-day mortality
timeFrame: 7 days
measure: Ventilator free days
timeFrame: 28 days
measure: Vasopressor free days
timeFrame: 28 days
measure: Total amount of fluid administration
timeFrame: 3 day, 7 day, 28 day
measure: Total fluid balance
timeFrame: 28 days
measure: Maximum dose of vasopressor use
timeFrame: 28 days
measure: Renal replacement therapy
timeFrame: 28 days
measure: Safety-related parameters
timeFrame: 28 days
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
References: