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

NCT03654001 | Completed Phase 3 DMC

• 1 other identifier: RF-2016-02361583
• Study Type: interventional
• Target: 1,319
• Locations: 1 country
• Sites: 37

Brief Summary

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.

Conditions

Septic Shock

Keywords

Septic Shock; Albumin; Balanced crystalloids

Outcome Measures

Primary Outcomes (2)

• All-cause 90-day mortality

  All-cause death from randomization to 90 days

  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).

  Up to 90 days

Secondary Outcomes (12)

• ICU mortality

  Up to ICU discharge, a median of 9 days

• In-hospital mortality

  Up to hospital discharge, a median of 20 days

• 1-year mortality

  Up to 1 year

• SOFA score

  Up to 90 days or ICU discharge - a median of 9 days - whichever comes first

• Incidence of AKI during ICU stay

  Up to 90 days or ICU discharge - a median of 9 days - whichever comes first

Other Outcomes (2)

• Severe metabolic acidosis

  Up to 90 days or ICU discharge - a median of 9 days - whichever comes first

• Severe hyperkalemia

  Up to 90 days or ICU discharge - a median of 9 days - whichever comes first

Study Arms (4)

Albumin + Balanced

EXPERIMENTAL

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. Balanced crystalloid solutions According to the preference and the standard use of the participating center: * Ringer Lactate * Ringer Acetate * Crystalsol

Biological: Albumin; Other: Balanced

Albumin + Saline

EXPERIMENTAL

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. Normal Saline Na+ 154 mEq/L, Cl- 154 mEq/L (0.9% NaCl).

Biological: Albumin

Balanced

EXPERIMENTAL

Balanced crystalloid solutions (Ringer Lactate, Ringer Acetate, Crystalsol)

Other: Balanced

Saline

NO INTERVENTION

Normal Saline Na+ 154 mEq/L, Cl- 154 mEq/L (0.9% NaCl).

Interventions

Albumin BIOLOGICAL

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.

Albumin + Balanced; Albumin + Saline

Balanced OTHER

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

Also known as: Ringer Lactate, Ringer Acetate, Crystalsol

Albumin + Balanced; Balanced

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with septic shock if they meet the two following criteria:
• Presence of an infection (known or suspected) in at least one site:
• Lung
• Abdomen
• Urinary tract
• Others (blood, skin and soft tissues, central nervous system, bones and joints, cardiac system, reproductive organs).
• 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.

You may not qualify if:

• Age \< 18 years
• Moribund state
• Known or suspected adverse reaction to albumin administration
• Septic shock in patients with traumatic brain injury or a clinically active cerebral lesion (known or suspected)
• Severe congestive heart failure (NYHA III and IV classes)
• 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)
• More than 24 hours after the onset of septic shock
• Religious objection to the administration of human blood products
• Presence of chronic end-stage renal disease
• Severe hyperkalemia (\> 6 mmol/L)
• Known or suspected pregnancy based on patient information
• Enrollment in other experimental interventional studies
• Laboratory confirmation for SARS-CoV-2 infection

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• Istituto Di Ricerche Farmacologiche Mario Negri: collaborator

Study Sites (37)

Ospedali Riuniti di Ancona

Ancona, AN, 60126, Italy

Location

AOU Policlinico di Bari

Bari, BA, 70124, Italy

Location

ASST Papa Giovanni XXIII

Bergamo, BG, 24127, Italy

Location

ASST BG Est - Ospedale Bolognini

Seriate, BG, 24068, Italy

Location

AST BG Ovest - PO Treviglio

Treviglio, BG, 24047, Italy

Location

Policlinico Sant'Orsola-Malpighi

Bologna, BO, 40138, Italy

Location

Azienda Ospedaliero - Universitaria di Ferrara - Arcispedale Sant'Anna

Cona, FE, 44124, Italy

Location

Ospedale del Mugello

Borgo San Lorenzo, FI, 50032, Italy

Location

Ospedale San Giuseppe

Empoli, FI, 50053, Italy

Location

AOU Careggi

Florence, FI, 50134, Italy

Location

Ospedale Colline dell'Albegna

Orbetello, GR, 58045, Italy

Location

Presidio Ospedaliero di Desio

Desio, MB, 20039, Italy

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza, MB, Italy

Location

ASST Nord Milano - Ospedale Bassini

Cinisello Balsamo, MI, 20092, Italy

Location

ASST Ovest Milano

Legnano, MI, 20025, Italy

Location

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Milan, MI, 20122, Italy

Location

ASST Fatebenefratelli - Sacco P.O. Sacco

Milan, MI, 20157, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, MI, 20162, Italy

Location

IRCCS Policlinico San Donato

San Donato Milanese, MI, 20097, Italy

Location

Azienda Ospedaliero-Universitaria di Modena, Policlinico di Modena

Modena, MO, 41125, Italy

Location

AOU Policlinico Paolo Giaccone

Palermo, PA, 90127, Italy

Location

ISMETT

Palermo, PA, 90127, Italy

Location

AOU Pisana

Pisa, PI, 56126, Italy

Location

As FO Azienda sanitaria Friuli Occidentale

Pordenone, PN, 33170, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, PV, 27100, Italy

Location

IRCCS ASMN Reggio Emilia

Reggio Emilia, RE, 43123, Italy

Location

Ospedale Infermi di Rimini

Rimini, Rimini, 47923, Italy

Location

Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore

Roma, RM, 00168, Italy

Location

Ospedale Santa Chiara

Trento, TN, 38122, Italy

Location

Ospedale Santa Croce

Moncalieri, TO, 10024, Italy

Location

Azienda Ospedaliero - Universitaria S. Luigi Gonzaga

Orbassano, TO, 10043, Italy

Location

AOU Città della Salute e della Scienza di Torino

Torino, TO, 10126, Italy

Location

ASU Giuliano Isontina

Trieste, TS, 34128, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine

Udine, UD, 33100, Italy

Location

Ospedale di Circolo e Fondazione Macchi

Varese, VA, 21100, Italy

Location

Azienda Ospedaliera Universitaria Integrata di Verona

Verona, VR, 37126, Italy

Location

Ospedale SS. Antonio e Biagio e Cesare Arrigo

Alessandria, 15121, Italy

Location

Related Publications (5)

• Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, Fanizza C, Caspani L, Faenza S, Grasselli G, Iapichino G, Antonelli M, Parrini V, Fiore G, Latini R, Gattinoni L; ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014 Apr 10;370(15):1412-21. doi: 10.1056/NEJMoa1305727. Epub 2014 Mar 18.

  PMID: 24635772 BACKGROUND

• SAFE Study Investigators; Finfer S, McEvoy S, Bellomo R, McArthur C, Myburgh J, Norton R. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med. 2011 Jan;37(1):86-96. doi: 10.1007/s00134-010-2039-6. Epub 2010 Oct 6.

  PMID: 20924555 BACKGROUND

• Mehlman DJ, Bulkley BH, Wiernik PH. Serum alpha-1-fetoglobulin with gastric and prostatic carcinomas. N Engl J Med. 1971 Nov 4;285(19):1060-1. doi: 10.1056/NEJM197111042851907. No abstract available.

  PMID: 4106199 BACKGROUND

• Semler MW, Self WH, Rice TW. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018 May 17;378(20):1951. doi: 10.1056/NEJMc1804294.

  PMID: 29768150 BACKGROUND

• Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. No abstract available.

  PMID: 23984731 BACKGROUND

MeSH Terms

Conditions

Shock, Septic

Interventions

Albumins; Ringer's Lactate

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Pietro Caironi, MD

  AOU S. Luigi Gonzaga, Orbassano

  PRINCIPAL INVESTIGATOR

• Giacomo Grasselli, MD

  Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2-by-2 factorial design, open-label, multicenter, randomized, controlled trial, 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 groups (Albumin + BAL, Albumin + NS, BAL, NS).

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 31, 2018
• Study Start: May 7, 2019
• Primary Completion: October 31, 2024
• Study Completion: January 31, 2025
• Last Updated: March 5, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (37)