Volume Replacement With Albumin in Severe Sepsis

NCT00707122 | Completed Phase 3 DMC

• 1 other identifier: ALBIOS
• Study Type: interventional
• Target: 1,818
• Locations: 1 country
• Sites: 1

Brief Summary

BACKGROUND The association between mortality and hypoalbuminemia has been observed in several diseases. Nonetheless, the efficacy of albumin on survival in critically ill patients is controversial. Several meta-analyses have reported either negative, neutral, or beneficial effects of albumin administration. To clarify this controversy, a large multicenter prospective study has been performed, comparing the effects of 4% albumin vs. saline for volume replacement in critically ill patients. Although no difference in the overall mortality has been observed, a predefined subgroup analysis has shown a trend of longer survival in septic patients treated with albumin. As fluid replacement has been shown to be critical in sepsis, and based on both its primary (oncotic) and secondary properties (anti-inflammatory), it is conceivable that the use of albumin for volume replacement and for treating hypoalbuminemia may have a beneficial effects on survival of septic patients. OBJECTIVES Primary objective: to verify whether volume replacement with albumin (treated group) and its maintenance within plasmatic physiologic range (equal or above 30 g/l) improves survival of patients with severe sepsis of septic shock, as compared to crystalloids (control group). Secondary objectives: to verify the differences in organ dysfunctions, hospital and intensive care unit (ICU) length of stay between the treated and control group. METHODS About 1350 patients with severe sepsis or septic shock will be randomized to receive either albumin or crystalloids as fluid therapy. Volume replacement will be performed for both groups according to the early-goal directed therapy. Treated group will receive 60 gr albumin infusion after randomization, and 40-60 gr albumin daily infusion to maintain serum album level equal or above 30 g/l. Control group will receive crystalloids for the entire study; albumin administration will be allowed only when daily serum albumin level will be lower than 15 g/l. Patients will be treated until the 28th day after randomization or until ICU discharge, whichever comes first. EXPECTED RESULTS Primary outcomes: absolute risk reduction of overall mortality of 7.5% at 28th day, with a further control at 90th day, following randomization. Secondary outcomes: reduction of number and severity of organ dysfunctions (as assessed by the Sequential Organ Failure Assessment score), reduction of ICU and hospital length of stay.

Conditions

Severe Sepsis; Septic Shock

Keywords

serum albumin, severe sepsis, septic shock, fluid therapy, hypoalbuminemia, critically ill

Outcome Measures

Primary Outcomes (1)

• mortality rate at the 28th day after randomization, with a further control at 90th day.

  mortality at 28th and 90th day after randomization

Secondary Outcomes (3)

• Number and severity of organ dysfunction (as recorded by the SOFA score)

  At 28th day after randomization and at ICU discharge

• ICU length of stay

  ICU discharge

• Hospital length of stay

  Hospital discharge

Study Arms (2)

1, Albumin and Crystalloids

OTHER

Treatment

Other: Albumin and Crystalloids

2, Crystalloids

OTHER

Control

Other: Crystalloids

Interventions

Albumin and Crystalloids OTHER

From day 2 to day 28 (or until ICU discharge, whichever comes first), fluid will be administered as follows: 1\. treated group: albumin will be infused on a daily basis, aimed to maintain its serum concentration equal or above 30 g/l (8). In particular, after the daily determination of its serum level: 1. if lower than 25 g/l, 300 ml of 20% of albumin solution (total amount of 60 gr) will be infused; 2. if equal or higher than 25 g/l and below 30 g/l, 200 ml of 20% of albumin solution (total amount of 40 gr) will be infused; 3. if higher than or equal to 30 g/l, no albumin will be infused. Albumin solutions will be infused over a period of 3 hours. Further infusion of crystalloids will be allowed, when necessary, according to the clinical judgment. No infusion of colloids, other than albumin, will be admitted.

1, Albumin and Crystalloids

Crystalloids OTHER

Volume replacement will be performed in both the treated and the control group according to the "early-goal directed therapy". control group: crystalloids infusion will be allowed whenever necessary on a clinical basis. Albumin administration will be restricted to emergency use, as clinically judged and documented according to the standard criteria of each participating unit. No other colloids will be allowed.

2, Crystalloids

Eligibility Criteria

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

You may qualify if:

• Patients with severe sepsis or septic shock, if each one of the following criteria is satisfied:
• Proved or suspected infection in at least one site:
• lung
• abdomen
• genito-urinary tract
• other (blood, skin and soft tissue, central nervous system, bones and joints, cardiac system, catheter-related infection, other)
• Two or more of the following:
• a core temperature ≥ 38° C o ≤ 36° C
• a heart rate ≥ 90 beats/min
• a respiratory rate ≥ 20 breaths/min or PaCO2 ≤ 32 mmHg or use of mechanical ventilation for an acute process
• a white blood cell count ≥ 12000/ml or ≤ 4000/ml or immature neutrophils \> 10%
• Presence of at least a severe organ dysfunction, as measured by the modified Sequential Organ Failure Assessment (SOFA) score:
• respiratory score \> 1
• hematologic score \> 1
• hepatic score \> 1

You may not qualify if:

• Age below 18 years
• Terminal state
• Known adverse reaction to albumin administration
• Severe sepsis or septic shock in patients after proved or suspected head injury, clinically active
• Congestive heart failure (NYHA score III and IV)
• Pathological conditions in which albumin administration is clinically indicated (hepatic cirrhosis with ascites, intestinal malabsorption syndrome, nephritic syndrome, burns)
• Religious objection to the administration of human blood products

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead

Study Sites (1)

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico; Via F. Sforza 35

Milan, 20135, Italy

Location

Related Publications (9)

• Alagna L, Meessen JMTA, Bellani G, Albiero D, Caironi P, Principale I, Vivona L, Grasselli G, Motta F, Agnelli NM, Parrini V, Romagnoli S, Keim R, Di Marzo Capozzi F, Taccone FS, Taccone W, Bottazzi B, Bandera A, Cortegiani A, Latini R. Higher levels of IgA and IgG at sepsis onset are associated with higher mortality: results from the Albumin Italian Outcome Sepsis (ALBIOS) trial. Ann Intensive Care. 2021 Nov 26;11(1):161. doi: 10.1186/s13613-021-00952-z.

  PMID: 34825972 DERIVED

• Piotti A, Novelli D, Meessen JMTA, Ferlicca D, Coppolecchia S, Marino A, Salati G, Savioli M, Grasselli G, Bellani G, Pesenti A, Masson S, Caironi P, Gattinoni L, Gobbi M, Fracasso C, Latini R; ALBIOS Investigators. Endothelial damage in septic shock patients as evidenced by circulating syndecan-1, sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS. Crit Care. 2021 Mar 19;25(1):113. doi: 10.1186/s13054-021-03545-1.

  PMID: 33741039 DERIVED

• Bonaventura A, Carbone F, Vecchie A, Meessen J, Ferraris S, Beck E, Keim R, Minetti S, Elia E, Ferrara D, Ansaldo AM, Novelli D, Caironi P, Latini R, Montecucco F. The role of resistin and myeloperoxidase in severe sepsis and septic shock: Results from the ALBIOS trial. Eur J Clin Invest. 2020 Oct;50(10):e13333. doi: 10.1111/eci.13333. Epub 2020 Jul 13.

  PMID: 32585739 DERIVED

• Carbone F, Bonaventura A, Vecchie A, Meessen J, Minetti S, Elia E, Ferrara D, Ansaldo AM, Tulli G, Guarducci D, Rossi N, Bona F, Ferrari M, Caironi P, Latini R, Montecucco F. Early osteopontin levels predict mortality in patients with septic shock. Eur J Intern Med. 2020 Aug;78:113-120. doi: 10.1016/j.ejim.2020.04.035. Epub 2020 May 11.

  PMID: 32409206 DERIVED

• Vasques F, Duscio E, Romitti F, Pasticci I, Caironi P, Meessen J, Latini R, Cressoni M, Camporota L, Pesenti A, Fumagalli R, Quintel M, Gattinoni L. Septic shock-3 vs 2: an analysis of the ALBIOS study. Crit Care. 2018 Sep 27;22(1):237. doi: 10.1186/s13054-018-2169-8.

  PMID: 30261898 DERIVED

• Protti A, Masson S, Latini R, Fumagalli R, Romero M, Pessina C, Pasetti G, Tognoni G, Pesenti A, Gattinoni L, Caironi P. Persistence of Central Venous Oxygen Desaturation During Early Sepsis Is Associated With Higher Mortality: A Retrospective Analysis of the ALBIOS Trial. Chest. 2018 Dec;154(6):1291-1300. doi: 10.1016/j.chest.2018.04.043. Epub 2018 May 19.

  PMID: 29787743 DERIVED

• Caironi P, Latini R, Struck J, Hartmann O, Bergmann A, Maggio G, Cavana M, Tognoni G, Pesenti A, Gattinoni L, Masson S; ALBIOS Study Investigators. Circulating Biologically Active Adrenomedullin (bio-ADM) Predicts Hemodynamic Support Requirement and Mortality During Sepsis. Chest. 2017 Aug;152(2):312-320. doi: 10.1016/j.chest.2017.03.035. Epub 2017 Apr 12.

  PMID: 28411114 DERIVED

• Ferrario M, Cambiaghi A, Brunelli L, Giordano S, Caironi P, Guatteri L, Raimondi F, Gattinoni L, Latini R, Masson S, Ristagno G, Pastorelli R. Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach. Sci Rep. 2016 Feb 5;6:20391. doi: 10.1038/srep20391.

  PMID: 26847922 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic; Hypoalbuminemia; Critical Illness

Interventions

Albumins; Crystalloid Solutions

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Hypoproteinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes

Intervention Hierarchy (Ancestors)

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

Study Officials

• Luciano Gattinoni, MD

  Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche; Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

  PRINCIPAL INVESTIGATOR

• Pietro Caironi, MD

  Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche; Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

  STUDY CHAIR

• Antonio Pesenti, MD

  Dipartimento di Medicina Perioperatoria e Terapia Intensiva, Azienda Ospedaliera San Gerardo di Monza, Università degli Studi Milano-Bicocca

  STUDY CHAIR

• Roberto Fumagalli, MD

  Dipartimento di Medicina Perioperatoria e Terapia Intensiva, Azienda Ospedaliera San Gerardo di Monza, Università degli Studi Milano-Bicocca

  STUDY CHAIR

• Gianni Tognoni, MD

  Consorzio Mario Negri Sud, S. Maria Imbaro

  STUDY CHAIR

• Marilena Romero

  Consorzio Mario Negri Sud, S. Maria Imbaro

  STUDY CHAIR

• Roberto Latini, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY CHAIR

• Serge Masson

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: June 26, 2008
• First Posted: June 30, 2008
• Study Start: July 1, 2008
• Primary Completion: April 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 10, 2015

Record last verified: 2015-11

Locations

IT (1)