Octapharma News June 22, 2004

June 22nd, 2004

S.A.F.E. Study: Increasing Confidence for the use of Albumin in Intensive Care Patients

The results are in: There is no difference in 28-day mortality between critically ill patients treated with saline or albumin, according to the S.A.F.E. (Saline versus Albumin Fluid Evaluation) study published May 27, 2004 in the New England Journal of Medicine.

Increasing Confidence in the treatment options...
"As the biggest trial ever attempted in ICUs the S.A.F.E. Study was a very ambitious project, but the results are clear – for Intensive Care patients there is no increase in mortality when we compare albumin with saline, and either can be used safely." Simon Finfer, Chair of the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group (CTG)

The multicenter, randomised, double-blind trial involving almost 7000 critically ill patients in New Zealand and Australia provides the best evidence to date that physicians can adhere to their Hippocratic oath to "first, do no harm" when choosing to treat patients with albumin, whose unique biochemical properties have been under investigation for many years for their potential benefit over crystalloids in particular conditions and patient populations.

The use of albumin in intensive care has been a controversial issue since the publication of a meta-analysis including 24 studies by the Cochrane Group that suggested that albumin could increase the risk of mortality. The validity of the Cochrane report has been debated since its publication. Dr. Simon Finfer, principal investigator of the S.A.F.E. study has pointed out that the Cochrane study on albumin was flawed because the studies included looked at different types of patients and different drugs. In addition to these comments, it has been noted that many of the 1300 randomized trials on albumin published since 1995 were conducted with fewer than 100 patients and only a small percentage of these were multicenter trials. The S.A.F.E. study marks a turning point in the design and control of clinical studies. “Albumin is widely used in ICUs across the world and there was a question mark over its safety. We felt it was vital to determine whether or not it increased mortality in critically ill patients as other researchers had suggested," said Simon Finfer.

The results of the S.A.F.E. study showed 28-day mortality was 21% in the saline group and 20.9% in the albumin group (relative risk (RR) of death was 0.99 for patients treated with albumin compared to those treated with saline). Secondary outcome measures included survival time during the first 28 days, changes in SOFA score, duration of mechanical ventilation, renal-replacement therapy, ICU and hospital stay. The results in these secondary outcome measures were also similar for both groups.

Related Story: Preliminary results and study methodology from S.A.F.E. were presented at several congresses including the International Society of Intensive Care and Emergency Medicine (ISICEM) congress in Brussels in March 2004. Octapharma reported on presentations given by the principal investigator Simon Finfer on April 13, 2004.

Now that the question of safety has been answered in a large heterogeneous population of ICU patients, the S.A.F.E. study suggests that the healthcare community must consider the differences in properties between crystalloids and colloids in order to determine efficacy in defined patient populations. The S.A.F.E. study points to a potential differences in physiological parameters in patients treated with albumin or saline that could impact survival in specific populations. While the S.A.F.E. study did not have the power to draw conclusive recommendations, differences in the relative risk of death among sepsis patients and patients with trauma were identified in the sub-group analysis.

The relative risk (RR) of death in patients with severe sepsis who received albumin vs saline was 0.87 (saline RR 1.05), pointing to a potential benefit from albumin. Opposite results were found in trauma patients with traumatic brain injury. Relative risk of death was 1.36 in the albumin group compared to the saline group (RR .96). However, excluding patients with traumatic brain injury resulted in no difference in mortality rates between saline and albumin among trauma patients. More studies are required to build the evidence in specific patient populations. The S.A.F.E. study investigators have discussed a follow up study on patients with traumatic brain injury, called "SAFE Brains."

"We have provided doctors working in intensive care with vastly superior scientific evidence to any they have had up to now,” said Dr Finfer. “Doctors around the world can now reliably use the results of the SAFE Study to guide them when deciding which of these fluids to use in the treatment of their patients,” adds Dr Finfer.

About Albumin

Albumin is a life-saving medication, derived from human plasma that has been used successfully for over 50 years to treat critically ill patients including those suffering from shock and burns. Albumin has previously shown to confer clinical benefit in special populations such as patients undergoing cardio-vascular surgery; however, these patients were excluded from the SAFE study (PPTA position on albumin).

Volume resusitation is achieved with less fluid when using albumin compared to saline (1:1.4 reported in the S.A.F.E. study). Albumin has several biological functions, in particular as a ligand binder. It also acts as an extracellular transition metal ion-binding and radical-scavenging antioxidant. In certain indications such as cardiac surgery and ascites, clear evidence indicates the cost-effectiveness of albumin. Calorie intake increases with albumin, while overall weight gain is reduced, compared to using crystalloids. For more information on the indications for 5% and 20% albumin, click here.

Useful References:
(Please note that clicking on the links below will take you outside of the Octapharma web site)

	The SAFE Study Investigators. A Comparison of Albumin and Saline for Fluid Resusutation in the Intensive Care Unit. N Engl J Med 2004 350: 2247-2256
	Media Release, May 27, 2004: World’s largest study in Intensive Care Australian research results provide answers for Doctors across the world. Australia and New Zealand Intensive Care Society.
	Cook D. Is albumin safe? N Engl J Med. 2004 May 27;350(22):2294-6. Editorial
	Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ 1998;317:235-40
	Liolios A. Volume Resuscutation: The Crystalloid vs Colloid Debate Revised. Medscape Conference Coverage, based on selected sessions at the 24th International Symposium on Intensive Care and Emergency Medicine. March 30, 2004 - April 2, 2004, Brussels, Belgium
	Quinlan GJ, Mumby S, Martin GS, Bernard GR, Gutteridge JM, Evans TW. Albumin influences total plasma antioxidant capacity favorably in patients with acute lung injury. Crit Care Med. 2004;32:755-759.
	Quinlan GJ, Margarson MP, Mumby S, et al. Administration of albumin to patients with sepsis syndrome: a possible beneficial role in plasma thiol repletion. Clin Sci. 1998;95:459-465.
	Sedrakyan A, Gondek K, Paltiel D, et al. Volume expansion with albumin decreases mortality after coronary artery bypass graft surgery. Chest. 2003;123:1853-1857.