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

NCT ID: NCT03654001

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1319 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-07
• Study Completion Date: 2025-01-31

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.

Detailed Description

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).

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Albumin + Balanced

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

Group Type: EXPERIMENTAL

Albumin

Intervention Type: 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.

Balanced

Intervention Type: 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).

Albumin + Saline

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).

Group Type: EXPERIMENTAL

Albumin

Intervention Type: 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.

Balanced

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

Group Type: EXPERIMENTAL

Balanced

Intervention Type: 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).

Saline

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Albumin

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.

Intervention Type: BIOLOGICAL

Balanced

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

Intervention Type: OTHER

Other Intervention Names

Ringer Lactate, Ringer Acetate, Crystalsol

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Di Ricerche Farmacologiche Mario Negri

OTHER

Sponsor Role: collaborator

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pietro Caironi, MD

Role: PRINCIPAL_INVESTIGATOR

AOU S. Luigi Gonzaga, Orbassano

Giacomo Grasselli, MD

Role: PRINCIPAL_INVESTIGATOR

Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda

Locations

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

Bologna, BO, Italy

Azienda Ospedaliero - Universitaria di Ferrara - Arcispedale Sant'Anna

Cona, FE, Italy

Ospedale del Mugello

Borgo San Lorenzo, FI, Italy

Ospedale San Giuseppe

Empoli, FI, Italy

AOU Careggi

Florence, FI, Italy

Ospedale Colline dell'Albegna

Orbetello, GR, Italy

Presidio Ospedaliero di Desio

Desio, MB, Italy

Fondazione IRCCS San Gerardo dei Tintori

Monza, MB, Italy

ASST Nord Milano - Ospedale Bassini

Cinisello Balsamo, MI, Italy

ASST Ovest Milano

Legnano, MI, Italy

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Milan, MI, Italy

ASST Fatebenefratelli - Sacco P.O. Sacco

Milan, MI, Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, MI, Italy

IRCCS Policlinico San Donato

San Donato Milanese, MI, Italy

Azienda Ospedaliero-Universitaria di Modena, Policlinico di Modena

Modena, MO, Italy

AOU Policlinico Paolo Giaccone

Palermo, PA, Italy

ISMETT

Palermo, PA, Italy

AOU Pisana

Pisa, PI, Italy

As FO Azienda sanitaria Friuli Occidentale

Pordenone, PN, Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, PV, Italy

IRCCS ASMN Reggio Emilia

Reggio Emilia, RE, Italy

Ospedale Infermi di Rimini

Rimini, Rimini, Italy

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

Roma, RM, Italy

Ospedale Santa Chiara

Trento, TN, Italy

Ospedale Santa Croce

Moncalieri, TO, Italy

Azienda Ospedaliero - Universitaria S. Luigi Gonzaga

Orbassano, TO, Italy

AOU Città della Salute e della Scienza di Torino

Torino, TO, Italy

ASU Giuliano Isontina

Trieste, TS, Italy

Azienda Sanitaria Universitaria Integrata di Udine

Udine, UD, Italy

Ospedale di Circolo e Fondazione Macchi

Varese, VA, Italy

Azienda Ospedaliera Universitaria Integrata di Verona

Verona, VR, Italy

Ospedale SS. Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

PMID: 24635772 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20924555 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 4106199 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29768150 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23984731 (View on PubMed)

Other Identifiers

RF-2016-02361583

Identifier Type: -

Identifier Source: org_study_id