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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
Date results information initially provided
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot trial of a hypertonic saline bolus in early sepsis
Scientific title
A pilot randomised trial comparing the inflammatory response to hypertonic saline versus normal saline as the initial fluid bolus in adults presenting to the emergency department with presumed early sepsis
Secondary ID [1] 263088 0
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis 270839 0
Condition category
Condition code
Infection 271019 271019 0 0
Other infectious diseases
Inflammatory and Immune System 271023 271023 0 0
Other inflammatory or immune system disorders

Study type
Description of intervention(s) / exposure
Single intravenous bolus of 5ml/kg of hypertonic (3%) saline solution
Intervention code [1] 269437 0
Treatment: Other
Comparator / control treatment
Single intravenous bolus of 10ml/kg of normal (0.9%) saline solution
Control group

Primary outcome [1] 279680 0
Circulating levels of interleukin-1 (used as an indicative inflammatory cytokine) compared to baseline level before fluid bolus. 3.5 mL serum tubes are collected from the patients at the requisite timepoints, allowed to stand at room temperature for 30 minutes to clot then centrifuged at 800g for 10 minutes at 4 deg C. Serum and plasma samples are aliquotted, stored immediately at -80 deg C and subsequently analysed using ELISA.
Timepoint [1] 279680 0
1, 3 and 24 hours after fluid bolus
Secondary outcome [1] 294186 0
Inflammatory gene activation and expression measured using qPCR compared to baseline level before fluid bolus. At the requisite timepoints 2.5mL PAXGene tubes are collected. The PAXgene tube is placed immediately at 4 deg C before being transferred to -20 deg C with 72 hours, and then transferred to -80 deg C for long-term storage and subsequent qPCR analysis.
Timepoint [1] 294186 0
1, 3 and 24 hours after fluid bolus
Secondary outcome [2] 294187 0
Bacterial load compared to baseline level before fluid bolus. Bacterial load is measured from PAXGene tubes as above.
Timepoint [2] 294187 0
1, 3 and 24 hours after fluid bolus
Secondary outcome [3] 294188 0
Haemodynamic parameters (e.g. mean arterial pressure, systolic pressure, heart rate measured non-invasively using standard equipment) compared to baseline level before fluid bolus
Timepoint [3] 294188 0
1, 3 and 24 hours after fluid bolus
Secondary outcome [4] 294189 0
Mortality measured by review of medical records and, where necessary, telephone follow up
Timepoint [4] 294189 0
28 days from enrolment

Key inclusion criteria
1. Suspected or proven infection
2. Two or more SIRS criteria (HR>90/min, RR>20/min, T>38 deg C, WCC>12 (or temp<36 deg C and WCC<4))
3. Fluid bolus indicated clinically
4. Informed consent
Minimum age
16 Years
Maximum age
No limit
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
1. Contraindication to volume loading (e.g. coexistent acute pulmonary oedema)
2. Severe hypotension (SBP<90) requiring immediate resuscitation
3. Plasma sodium concentration outside normal range (135-145 mEq/L)
4. Established significant metabolic acidosis (venous pH <7.25)
5. Established significant renal failure eGFR < 45 mL/min/1.73m2
6. Pregnancy
7. Age less than 16 years of age
8. Deemed for palliative/supportive care only
9. Received prehospital IV fluids >500 mL in total

Study design
Purpose of the study
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible patients will be identified by clinical staff working in the emergency department and , once informed consent is obtained, allocation will occur by logging on to a secure website that will randomise the patient to their treatment group. The staff identifying inclusion criteria is therefore unaware to which arm the patient will be randomised until after they consent the patient and log on to the website.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomised in real time utilising a web based randomisation system
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?

Intervention assignment
Other design features
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment status
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 269910 0
Name [1] 269910 0
Royal Perth Hospital
Address [1] 269910 0
GPO Box X2213
Perth WA
Country [1] 269910 0
Primary sponsor type
Royal Perth Hospital
GPO Box X2213
Perth WA
Secondary sponsor category [1] 268922 0
Name [1] 268922 0
Address [1] 268922 0
Country [1] 268922 0

Ethics approval
Ethics application status
Ethics committee name [1] 271878 0
Royal Perth Hospital HREC
Ethics committee address [1] 271878 0
GPO Box X2213
Perth WA
Ethics committee country [1] 271878 0
Date submitted for ethics approval [1] 271878 0
Approval date [1] 271878 0
Ethics approval number [1] 271878 0
EC 2011-091

Brief summary
Patients with sepsis have the potential to become very unwell in a rapid period. The progression from being moderately unwell to severely unwell may be due to the body’s immune system responding to the infection, rather than the infection itself.
A fundamental and accepted practice in the management of patients with suspected sepsis is the administration of intravenous fluids. There is no consensus that any particular fluid is better than the other. In particular, we do not know whether any time of fluid has a beneficial effect on this immune response to infection.
Hypertonic saline fluid has been shown in some animal and human studies to influence the immune response to infection. In this pilot study we will assess whether hypertonic saline has an advantage over normal saline in producing beneficial immunomodulation. If this can be shown, it will inform the design of a larger multicentre trial with clinical endpoints.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 33190 0
A/Prof Glenn Arendts
Address 33190 0
CCREM Emergency Department, Royal Perth Hospital GPO Box X2213 Perth WA 6847
Country 33190 0
Phone 33190 0
61 8 92248458
Fax 33190 0
Email 33190 0
Contact person for public queries
Name 16437 0
Ms Sophie Damianopoulos
Address 16437 0
Emergency Department, Royal Perth Hospital
GPO Box X2213
Perth WA 6847
Country 16437 0
Phone 16437 0
61 8 92248458
Fax 16437 0
Email 16437 0
Contact person for scientific queries
Name 7365 0
A/Prof Glenn Arendts
Address 7365 0
Emergency Department, Royal Perth Hospital
GPO Box X2213
Perth WA 6847
Country 7365 0
Phone 7365 0
61 8 92248458
Fax 7365 0
Email 7365 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
Trial was envisaged, designed and approved before these requirements became commonplace.The PICF for this trial clearly states that only the investigators will have access to participant data, and it is unethical to now share these data
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Journal publication details
Publication date and citation/details [1] 2951 0
J Crit Care. 2019 Aug;52:33-39. doi: 10.1016/j.jcrc.2019.03.009. (Epub 29/03/2019)
Attachments [1] 2951 0
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary