Volume Replacement With Albumin in Severe Sepsis

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

Interventions

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: 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.

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.

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

  lead OTHER

Principal Investigators

• Luciano Gattinoni, MD · Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche; Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

• Pietro Caironi, MD · Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche; Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

• Antonio Pesenti, MD · Dipartimento di Medicina Perioperatoria e Terapia Intensiva, Azienda Ospedaliera San Gerardo di Monza, Università degli Studi Milano-Bicocca

• Roberto Fumagalli, MD · Dipartimento di Medicina Perioperatoria e Terapia Intensiva, Azienda Ospedaliera San Gerardo di Monza, Università degli Studi Milano-Bicocca

• Gianni Tognoni, MD · Consorzio Mario Negri Sud, S. Maria Imbaro

• Marilena Romero · Consorzio Mario Negri Sud, S. Maria Imbaro

• Roberto Latini, MD · Istituto Di Ricerche Farmacologiche Mario Negri

• Serge Masson · Istituto Di Ricerche Farmacologiche Mario Negri

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-07-31

Primary Completion

2013-04-30

Completion

2013-10-31

Countries

• Italy

Study Locations