Plain English Summary
Background and study aims:
When a person is badly injured and there is significant loss of blood, one of the most important strategies for aiding recovery is to replace the lost volume of blood with suitable intravenous fluid (fluid resuscitation). There is considerable controversy regarding the nature of the fluid that should be used. Simple salt solutions (crystalloids) are widely used and are recommended on the basis that they are cheap and have few side effects. On the other hand, more complex solutions containing large molecules (colloids) designed to remain in the bloodstream longer are widely supported because they provide faster initial resuscitation with smaller volumes of fluid and this may lead to better outcomes, particularly in terms of swelling of the tissues (oedema). However, the colloids do have some side effects in that they are associated with an increased risk of bleeding, carry a very small risk of severe allergic reactions and have a possible association with kidney injury. The controversy between these two types of fluid relates to the fact that various studies have failed to demonstrate a consistent benefit from the use of colloids and that colloids are significantly more expensive. The aim of this study is to compare resuscitation with crystalloids and colloids in patients who have suffered severe injury (trauma), either blunt (e.g. motor vehicle accidents) or penetrating (e.g. gunshot or stab wounds). The intention is to study the amount of each fluid type required in either blunt or penetrating trauma and to investigate possible differences in patient outcomes as a result of the use of one type of fluid or the other.
Who can participate?
Patients aged 18 to 60 who have suffered sufficiently severe injuries to require a minimum of 3 litres of fluid resuscitation
What does the study involve?
Participants are randomly allocated to undergo fluid resuscitation using either standard crystalloid solution (normal salt solution) or a widely used colloid solution (hydroxy ethyl starch [HES]). All participants are otherwise treated identically in a manner appropriate to the injuries received. The main measurements to be made are the volumes of fluid required in the first 24 hours, including these study fluids, and the requirement for blood and blood products. The major outcome to study is the speed of recovery of bowel function after injury. Safety markers to examine include markers of kidney damage and measurements of blood clotting. In addition, other factors to measure include the length of stay in intensive care and markers of overall organ function.
What are the possible benefits and risks of participating?
Participants benefit from being treated by experts in the field from the moment they reach the hospital. Side effects from the crystalloid might include fluid overload, with tissue swelling and possible swelling in the abdominal area that may increase the risk of complications from the injury. Side effects related to the colloid might include increased risk of bleeding, a possibility of long-term skin itching and a possibility of kidney injury related to the colloid.
Where is the study run from?
Groote Schuur Hospital (South Africa)
When is the study starting and how long is it expected to run for?
December 2007 to December 2009
Who is funding the study
1. University of Cape Town (South Africa)
2. Fresenius-Kabi (Germany)
Who is the main contact?
Prof. Michael James
mike.james@uct.ac.za
Trial website
Contact information
Type
Scientific
Primary contact
Prof Michael James
ORCID ID
Contact details
Department of Anaesthesia
University of Cape Town
Anzio Road
Observatory
Western Cape
Cape Town
7925
South Africa
+27 (0)21 406 6143
mike.james@uct.ac.za
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Comparison of crystalloid-blood resuscitation with crystalloid-colloid-blood resuscitation in severe trauma patients: a randomised double-blind trial
Acronym
FIRST (Fluids In Resuscitation of Severe Trauma)
Study hypothesis
Colloid (hydroxyethyl starch HES 130/0.4 in saline) used for trauma resuscitation is superior to crystalloid (0.9% saline) solutions in terms of volumes required for resuscitation and consequent morbidity, particularly the recovery of gastrointestinal function and the incidence of complications.
Ethics approval
University of Cape Town Research Ethics Committee, 23/01/2007, ref: 217/2006
Study design
Randomised single-centre double-blind interventional study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Available in English/Afrikaans/Xhosa from mike.james@uct.ac.za
Condition
Severe blunt or penetrating trauma
Intervention
1. Intravenous fluid administration to haemodynamic and physiological endpoints as required, 0.9% saline
2. HES 130/0.4 in saline (Voluven®)
Time taken to achieve haemodynamic goals is recorded. Duration of treatment is until study endpoint (return of bowel function) is satisfied; follow-up for 30 days from enrolment or death.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
1. Volumes of fluids required to meet resuscitation goals over the first 24 hours from study entry
2. Time (days) until recovery of bowel function as determined by tolerance of oral of parenteral feeding
Secondary outcome measures
1. Days free of gastrointestinal dysfunction during first 30 days
2. Median and maximal sequential organ failure assessment (SOFA) score
3. Length of stay in Intensive Care Unit (LOS in ICU)
4. Fluid volumes used during initial surgical procedures
5. Time to initial achievement of resuscitation target values
6. Intra-abdominal pressure following resuscitation
7. Time to first passage of stool
Overall trial start date
06/12/2007
Overall trial end date
31/12/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients suffering severe trauma requiring at least 3 litres of estimated resuscitation fluid admitted to Groote Shuur Hospital Trauma Unit
2. Penetrating or blunt trauma (separately randomised)
3. Aged greater than 18 years and less than 60 years, either sex
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
140
Participant exclusion criteria
1. Fluid overload pulmonary oedema
2. Known allergy to hydroxyethyl starch
3. Known pre-existing renal failure with oliguria including anuria, severe intracranial bleeding, severe hypernatremia or severe hyperchloremia on admission
4. Severe head injury from which they are unlikely to recover
5. Severe crush injury
6. Unrecordable blood pressure unresponsive to 2 l fluid loading
7. Clinically obvious cardiac tamponade
8. Neurogenic shock (high spinal)
9. Known acquired immune deficiency syndrome (AIDS) or AIDS related complex
10. Patients receiving dialysis treatment
11. Patients admitted greater than 6 hours following injury
12. Patients who have already received non-study colloids
13. Patients taking part in another clinical trial at the same time
14. Patients refusing consent
Recruitment start date
06/12/2007
Recruitment end date
31/12/2009
Locations
Countries of recruitment
South Africa
Trial participating centre
University of Cape Town
Cape Town
7925
South Africa
Sponsor information
Organisation
University of Cape Town (South Africa)
Sponsor details
Department of Anaesthesia
Anzio Road
Observatory
Western Cape
7925
South Africa
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
University of Cape Town (South Africa) - supported by an unrestricted educational grant from Fresenius Kabi Deutschland GmbH (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
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
Basic results (scientific)
Publication list
1. 2011 results in http://bja.oxfordjournals.org/content/early/2011/08/19/bja.aer229