Volume Replacement With Albumin in Severe Sepsis - Full Text View

Sponsored by:	Fondazione Ospedale Maggiore Policlinico Milano
Information provided by:	Fondazione Ospedale Maggiore Policlinico Milano
ClinicalTrials.gov Identifier:	NCT00707122

Purpose

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.

Condition	Intervention	Phase
Severe Sepsis Septic Shock	Other: Albumin and Crystalloids Other: Crystalloids	Phase III

MedlinePlus related topics: Sepsis

Drug Information available for: Benzocaine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	Efficacy of Albumin Administration for Volume Replacement in Patients With Severe Sepsis or Septic Shock - the ALBumin Italian Outcome Sepsis (ALBIOS) Study

Further study details as provided by Fondazione Ospedale Maggiore Policlinico Milano:

Primary Outcome Measures:

mortality rate at the 28th day after randomization, with a further control at 90th day. [ Time Frame: mortality at 28th and 90th day after randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number and severity of organ dysfunction (as recorded by the SOFA score) [ Time Frame: At 28th day after randomization and at ICU discharge ] [ Designated as safety issue: No ]
ICU length of stay [ Time Frame: ICU discharge ] [ Designated as safety issue: No ]
Hospital length of stay [ Time Frame: Hospital discharge ] [ Designated as safety issue: No ]

Estimated Enrollment:	1350
Study Start Date:	July 2008
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1, Albumin and Crystalloids Treatment	Other: Albumin and Crystalloids 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: if lower than 25 g/l, 300 ml of 20% of albumin solution (total amount of 60 gr) will be infused; 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; 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.
2, Crystalloids Control	Other: Crystalloids 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.

Arms

Assigned Interventions

1, Albumin and Crystalloids

Treatment

Other: Albumin and Crystalloids

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:

if lower than 25 g/l, 300 ml of 20% of albumin solution (total amount of 60 gr) will be infused;
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;
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.

2, Crystalloids

Control

Other: Crystalloids

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.

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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
  - cardiovascular score equal to 1, 3 or 4
  - renal score > 1

Exclusion Criteria:

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)
More than 24 hours since inclusion criteria were met
Religious objection to the administration of human blood products
Inclusion in other experimental study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00707122

Contacts

Contact: Luciano Gattinoni, MD

+39 02 5503 3232

gattinon@policlinico.mi.it

Locations

Italy
Fondazione Ospedale Maggiore Policlinico Mangiagalli e Regina Elena	Recruiting
Milano, Italy, 20135
Contact: Luciano Gattinoni +390255033232 gattinon@policlinico.mi.it

Sponsors and Collaborators

Fondazione Ospedale Maggiore Policlinico Milano

Investigators

Principal Investigator:	Luciano Gattinoni, MD	Istituto di Anestesiologia e Rianimazione, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
Study Chair:	Pietro Caironi, MD	Istituto di Anestesiologia e Rianimazione, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
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

More Information

Responsible Party:	Fondazione Ospedale Maggiore Policlinico Milano ( Fondazione Ospedale Maggiore Policlinico Milano )
Study ID Numbers:	ALBIOS
Study First Received:	June 26, 2008
Last Updated:	October 27, 2008
ClinicalTrials.gov Identifier:	NCT00707122
Health Authority:	Italy: The Italian Medicines Agency

Keywords provided by Fondazione Ospedale Maggiore Policlinico Milano:

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

Study placed in the following topic categories:

Systemic Inflammatory Response Syndrome
Sepsis
Shock
Critical Illness

Hypoalbuminemia
Shock, Septic
Benzocaine
Inflammation

Additional relevant MeSH terms:

Pathologic Processes
Infection

ClinicalTrials.gov processed this record on January 16, 2009