Contact information
Type
Scientific
Primary contact
Prof Robyn Norton
ORCID ID
Contact details
The George Institute for International Health
Level 24
Maritime Trade Towers
207 Kent Street
Sydney
NSW 2021
Australia
+ 61 2 9657 0381
rnorton@george.org.au
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
153711
Study information
Scientific title
Acronym
SAFE Study (Saline versus Albumin Fluid Evaluation)
Study hypothesis
When 4% albumin is compared to 0.9% sodium chloride (normal saline) for intravascular fluid resuscitation in patients in the Intensive Care Unit (ICU) there is no difference in 28-day all-cause mortality.
Ethics approval
Ethics approval at Royal North Shore Hospital (affiliated with the University of Sydney and the Institute for International Health) was issued on 27 November 2000 (protocol ref: 0010-173M). Each participating institution also received ethics approval.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Critically ill patients requiring intravenous fluid resuscitation
Intervention
The study treatment will be randomly allocated with stratification within the ICU and across the study population for patients admitted for trauma causes or non-trauma causes. Administration of the study treatments will be double blinded. Each eligible participant will be randomised to receive either 4% human albumin or 0.9% sodium chloride.
Co-sponsor for this trial:
Australian and New Zealand Intensive Care Society Clinical Trials Group
Level 3, 10 Ievers Terrace
Carlton, Melbourne 3053
Australia
Phone: +61 3 9340 3400
Fax: +61 3 9340 3499
Contact person: Professor Simon Finfer (sfinfer@george.org.au)
Intervention type
Drug
Phase
Not Specified
Drug names
Human albumin solution or normal saline
Primary outcome measure
Death from all causes at 28 days after randomisation
Secondary outcome measures
1. Survival time during the first 28 days
2. The proportion of patients with one, two, three, four and five new organ failures (defined as documented change in cardiovascular, respiratory, renal, haematologic or hepatic component of the Sepsis-related Organ Failure [SOFA] score from zero, one or two at base-line to three or four during ICU stay)
3. Duration of mechanical ventilation
4. Duration of renal replacement therapy
5. Duration of ICU and hospital stay
Overall trial start date
01/01/2003
Overall trial end date
31/12/2004
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Patients are eligible for inclusion in the study if ALL the following requirements are met:
1. Fluid resuscitation is required for intravascular fluid depletion that is in addition to intravenous fluid that is required for nutrition or to replace ongoing insensible losses, urinary losses, ongoing losses from other sites (e.g., fistula losses from the gastrointestinal tract, urinary losses from diabetes insipidus, cerebral salt wasting syndrome or the polyuric phase of acute renal failure) or to restore normonatraemia
2. The ICU clinician considers that both 4% human albumin solution and 0.9% sodium chloride are equally appropriate for the patient and that no specific indication or contraindication for either exists
3. The requirement for fluid resuscitation must be supported by AT LEAST ONE of the following clinical signs:
a. Heart rate greater than 90 beats/min
b. Systolic Blood Pressure (SBP) less than 100 mmHg or Mean Arterial Pressure (MAP) less than 75 mmHg or a 40 mmHg decrease in SBP or MAP from the baseline recording
c. Central venous pressure less than 10 mmHg
d. Pulmonary artery wedge pressure less than 12 mmHg
e. Respiratory variation in systolic or mean arterial blood pressure of greater than 5 mmHg
f. Capillary refill time greater than one second
g. Urine output less than 0.5 ml/kg for one hour
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
7000
Participant exclusion criteria
Patients are excluded from the study if one or more of the following are present:
1. A known previous adverse reaction to human albumin solution
2. Any known religious objection to the administration of human blood products (for example if patient is a Jehovahs Witness)
3. A requirement for the patient to receive plasmapheresis during this ICU admission
4. An admission to the ICU following cardiac surgery
5. An admission to the ICU for the treatment of body burn
6. An admission to the ICU following liver transplantation surgery
7. Age less than 18 years
8. Brain death or brain death that is likely to be diagnosed within in the next 24 hours of fluid resuscitation being required
9. If the patient is moribund and expected to die within the next 24 hours - defined as having a treatment limitation order in place that exceeds a not for resuscitation order and that indicates the treating clinicians are not committed to full supportive care
10. If the patient has previously been enrolled and has completed follow up in the SAFE study
11. If the patient has previously received fluid resuscitation that was prescribed within the study ICU and during this current ICU admission
12. If the patient has been transferred to the study ICU from a non-study ICU and received a fluid bolus or fluid resuscitation for the treatment of volume depletion in that non-study ICU
Recruitment start date
01/01/2003
Recruitment end date
31/12/2004
Locations
Countries of recruitment
Australia, New Zealand
Trial participating centre
The George Institute for International Health
Sydney
NSW 2021
Australia
Sponsor information
Organisation
The George Institute for International Health (Australia)
Sponsor details
c/o Professor Simon Finfer
The George Institute for International Health
Level 24
Maritime Trade Towers
207 Kent Street
Sydney
NSW 2021
Australia
Sponsor type
Research organisation
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Funding has been from several organisations (listed in alphabetical order):
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Location
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Auckland Hospital (New Zealand)
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Commonwealth Department of Health and Aged Care (Australia)
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CSL Limited, Melbourne (Australia)
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Middlemore Hospital, Auckland (New Zealand)
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National Health and Medical Research Council (Australia) - three year project grant (ref: 153711)
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National Health Research Council (New Zealand) (ref: 01/386)
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New South Wales Health Department
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Northern Territory Health Services (Australia) - grant from the Australian Health Care Agreement 1998 - 2003 Quality Improvement and Enhancement Funds
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Queensland Health Services Department (Australia)
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Royal Hobart Hospital, Tasmania (Australia)
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South Australia Department of Human Services (Australia)
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Victoria Department of Human Services (Australia)
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Western Australia Health Department (Australia)
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The SAFE study was initiated and designed by the Australian and New Zealand Intensive Care Society Clinical Trials Group and the Australian and Red Cross Blood Service. The study design, protocol and procedures have been finalised in collaboration with the Institute for International Health, independently of the aforementioned funding bodies. The data will be collected, analysed and published independent of the funding bodies and a copy of the final report will be distributed to them on completion of the study.
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Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
Results on:
1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17040925
2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17761591
Publication citations
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, Finfer S, Bellomo R, McEvoy S, Lo SK, Myburgh J, Neal B, Norton R, Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the saline versus albumin fluid evaluation (SAFE) study., BMJ, 2006, 333, 7577, 1044, doi: 10.1136/bmj.38985.398704.7C.
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, , , , Myburgh J, Cooper DJ, Finfer S, Bellomo R, Norton R, Bishop N, Kai Lo S, Vallance S, Saline or albumin for fluid resuscitation in patients with traumatic brain injury., N. Engl. J. Med., 2007, 357, 9, 874-884, doi: 10.1056/NEJMoa067514.