ALBumin Italian Outcome Septic Shock-BALANCED Trial (ALBIOSS-BALANCED)

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico1,319 enrolled

Overview

Septic shock is a devastating condition often observed in ICU. It is characterized by pro-inflammatory and immune responses, organ failures, high incidence of AKI and lethality. Fluid resuscitation is pivotal as supportive therapy. At present, there are no effective therapies to improve survival of such clinical condition, often characterized by a mortality as high as 40% during the first 90 days from diagnosis. This project proposes a large 2-by-2 factorial randomized clinical trial testing the efficacy of albumin and the low- chloride balanced crystalloid solutions (either Ringer Lactate, Ringer Acetate, or Crystalsol - BAL) in septic shock. The investigators have recently concluded a multicenter, randomized trial, the ALBIOS trial, in which, in a post-hoc analysis, albumin, in addition to crystalloids, reduced 90-day mortality in patients with septic shock, as compared to crystalloids alone (Caironi P et al, 2014). Crystalloids with supra-physiological chloride content may deteriorate renal perfusion, increasing the risk of acute kidney injury (AKI) and mortality.

The project will consist of a 2-by-2 factorial, investigator-initiated, open-label, multicenter, randomized, controlled trial, with PROBE design (Prospective Randomized Open Trial with Blinded Evaluation of Outcomes), in patients with septic shock, as defined according to clinical criteria. Patients will be randomized in a 1:1:1:1 ratio to one of the 4 study groups (Albumin + BAL, Albumin + NS, BAL, NS). Both the primary endpoints will include events evaluated objectively: 90-day mortality and incidence of AKI, as assessed by KDIGO criteria (KDIGO Acute Kidney Injury Work Group, 2012).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,319

Interventions

AlbuminBIOLOGICAL

Human Albumin In parallel with fluid administration for volume resuscitation, patients will receive 400 ml of 20% albumin solution both at randomization (D0) and at day 1 (D1). Subsequently, from day 2 (D2) until day 90 (D90) or ICU discharge (whichever comes first), 20% albumin will be administered on a daily basis, to maintain serum albumin concentration equal to or greater than 30 g/L, based upon serum albumin determination.

BalancedOTHER

Balanced crystalloid solutions are traditionally crystalloid solutions containing a relatively low concentration of chloride as compared to 0.9% NaCl containing solutions (Normal Saline).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: Patients with septic shock if they meet the two following criteria: 1. Presence of an infection (known or suspected) in at least one site: 1. Lung 2. Abdomen 3. Urinary tract 4. Others (blood, skin and soft tissues, central nervous system, bones and joints, cardiac system, reproductive organs). 2. Presence of a severe and acute, sepsis-related cardiovascular failure (as assessed by the SOFA score - see Annex 1), requiring vasopressor to maintain mean arterial pressure \>=65 mmHg, despite adequate volume resuscitation a) Cardiovascular SOFA score \> 2 (3 or 4) If the patient is unable to provide informed consent, she/he can be included in the trial provided that the requirements of ongoing laws are fulfilled; details on this approach are provided in the protocol, par 11.1 and related Annex 3. The patient will be informed about having been included in a clinical trial, as soon as she/he will regain consciousness. Exclusion Criteria: 1. Age \< 18 years 2. Moribund state 3. Known or suspected adverse reaction to albumin administration 4. Septic shock in patients with traumatic brain injury or a clinically active cerebral lesion (known or suspected) 5. Severe congestive heart failure (NYHA III and IV classes) 6. Clinical situations in which the use of albumin is known or supposed to be clinically beneficial (hepatic cirrhosis with ascites, malabsorption syndrome or protein-losing enteropathy, nephrotic syndrome, burns) 7. More than 24 hours after the onset of septic shock 8. Religious objection to the administration of human blood products 9. Presence of chronic end-stage renal disease 10. Severe hyperkalemia (\> 6 mmol/L) 11. Known or suspected pregnancy based on patient information 12. Enrollment in other experimental interventional studies 13. Laboratory confirmation for SARS-CoV-2 infection

Locations (37)

Ospedali Riuniti di Ancona

Ancona, AN, Italy

AOU Policlinico di Bari

Bari, BA, Italy

ASST Papa Giovanni XXIII

Bergamo, BG, Italy

ASST BG Est - Ospedale Bolognini

Seriate, BG, Italy

AST BG Ovest - PO Treviglio

Treviglio, BG, Italy

Policlinico Sant'Orsola-Malpighi

Outcomes

Primary Outcomes

All-cause 90-day mortality

All-cause death from randomization to 90 days

Time frame: Up to 90 days

Combined co-primary endpoint

The composite of all-cause death from randomization to 90 days and new occurrence of acute kidney injury (AKI).

Time frame: Up to 90 days

Secondary Outcomes

ICU mortality

All-cause death occurring in Intensive Care Unit (ICU)

Time frame: Up to ICU discharge, a median of 9 days

In-hospital mortality

All-cause death occurring during hospital stay

Time frame: Up to hospital discharge, a median of 20 days

1-year mortality

All-cause death from randomization to 1 year

Time frame: Up to 1 year

SOFA score

Severity and incidence of organ failures, as assessed by the Sequential Organ Failure Assessment (SOFA) score. SOFA score is used to determine the extent of organ function in a patient while in the intensive care unit. The score is based on 6 different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. The scale of each score ranges from 0 (no dysfunction) to 4 (maximal dysfunction). The 6 scores are then added up to provide a global score: the highest the value, the worst the condition of the patient.