Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611001021965
Ethics application status
Approved
Date submitted
22/09/2011
Date registered
23/09/2011
Date last updated
10/07/2019
Date data sharing statement initially provided
10/07/2019
Date results information initially provided
10/07/2019
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
Nil
Universal Trial Number (UTN)
U1111-1124-7095
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

Intervention/exposure
Study type
Interventional
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
Active

Outcomes
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

Eligibility
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
Sex
Both males and females
Can healthy volunteers participate?
No
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
Treatment
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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2011
Actual
19/11/2011
Date of last participant enrolment
Anticipated
Actual
5/04/2015
Date of last data collection
Anticipated
Actual
5/05/2015
Sample size
Target
70
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 269910 0
Hospital
Name [1] 269910 0
Royal Perth Hospital
Country [1] 269910 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
GPO Box X2213
Perth WA
6847
Country
Australia
Secondary sponsor category [1] 268922 0
None
Name [1] 268922 0
Address [1] 268922 0
Country [1] 268922 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271878 0
Royal Perth Hospital HREC
Ethics committee address [1] 271878 0
GPO Box X2213
Perth WA
6847
Ethics committee country [1] 271878 0
Australia
Date submitted for ethics approval [1] 271878 0
06/07/2011
Approval date [1] 271878 0
12/09/2011
Ethics approval number [1] 271878 0
EC 2011-091

Summary
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

Contacts
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
Australia
Phone 33190 0
61 8 92248458
Fax 33190 0
Email 33190 0
glenn.arendts@uwa.edu.au
Contact person for public queries
Name 16437 0
Ms Sophie Damianopoulos
Address 16437 0
CCREM
Emergency Department, Royal Perth Hospital
GPO Box X2213
Perth WA 6847
Country 16437 0
Australia
Phone 16437 0
61 8 92248458
Fax 16437 0
Email 16437 0
sophie.damianopoulos@health.wa.gov.au
Contact person for scientific queries
Name 7365 0
A/Prof Glenn Arendts
Address 7365 0
CCREM
Emergency Department, Royal Perth Hospital
GPO Box X2213
Perth WA 6847
Country 7365 0
Australia
Phone 7365 0
61 8 92248458
Fax 7365 0
Email 7365 0
glenn.arendts@uwa.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes J Crit Care. 2019 Aug;52:33-39. doi: 10.1016/j.jcr... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseBolus therapy with 3% hypertonic saline or 0.9% saline in emergency department patients with suspected sepsis: A pilot randomised controlled trial.2019https://dx.doi.org/10.1016/j.jcrc.2019.03.009
N.B. These documents automatically identified may not have been verified by the study sponsor.