Condition category
Signs and Symptoms
Date applied
19/09/2002
Date assigned
19/09/2002
Last edited
05/09/2007
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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 Jehovah’s 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

http://www.thegeorgeinstitute.org

Funders

Funder type

Hospital/treatment centre

Funder name

Funding has been from several organisations (listed in alphabetical order):

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Auckland Hospital (New Zealand)

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Funder name

Commonwealth Department of Health and Aged Care (Australia)

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CSL Limited, Melbourne (Australia)

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Funder name

Middlemore Hospital, Auckland (New Zealand)

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Funder name

National Health and Medical Research Council (Australia) - three year project grant (ref: 153711)

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Location

Funder name

National Health Research Council (New Zealand) (ref: 01/386)

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Funder name

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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Funder name

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.

Alternative name(s)

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Location

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

Results - basic reporting

Publication summary

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

  1. , 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.

  2. , , , , 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.

Additional files

Editorial Notes