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Trial registered on ANZCTR


Registration number
ACTRN12615000158561
Ethics application status
Approved
Date submitted
6/02/2015
Date registered
18/02/2015
Date last updated
2/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot, randomized, blinded, multi-centre, feasibility, safety and biochemical and physiological study of normal saline versus plasmalyte in intensive therapy
Scientific title
A multi-centre randomized clinical trial involving normal saline versus plasmalyte intravenous fluid solutions for patients admitted to the intensive care unit
Secondary ID [1] 286118 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Pilot ICU SPLIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical Illness 294119 0
Condition category
Condition code
Other 294435 294435 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We plan to enrol 60 patients (30 treated with normal saline and 30 treated with plasmalyte) and to use base excess during the first four days of intensive care admission as the primary outcome.

Eligible patients will be aged 18 years or greater, admitted to the intensive care unit and require fluid resuscitation.

Patients will then receieve either the study fluid either (a) intravenous normal saline 0.9% or (b) intravenous plasmalyte 148) from the time of enrollment in the intensive care unit until discharge from the intensive care unit. All other clinical care decisions and management decisions will be those of the patient's treating clinical team.
Intervention code [1] 291116 0
Treatment: Other
Comparator / control treatment
Patients are their own controls and will receive only 0.9% normal saline or Plasmalyte 148 as a blinded study fluid. Both study fluids are considered standard care in Australian intensive care units.
Control group
Active

Outcomes
Primary outcome [1] 294231 0
Base excess as obtained from routine pathology testing and assessed via medical record review
Timepoint [1] 294231 0
Daily from ICU admission until day four of ICU care.
Secondary outcome [1] 312847 0
Acute kidney injury as per the RIFLE criteria as obtained from routine pathology testing and assessed via medical record review
Timepoint [1] 312847 0
Daily changes in the patient's serum creatinine, serum chloride and urinary output occurring from the admission to ICU until ICU discharge
Secondary outcome [2] 312848 0
Delta creatine (the difference between baseline and peak creatinine) as determined by medical record review
Timepoint [2] 312848 0
Daily from ICU admission until ICU discharge
Secondary outcome [3] 312849 0
Requirement for renal replacement therapy assessed via medical record review
Timepoint [3] 312849 0
Daily from admission to ICU through to discharge from ICU
Secondary outcome [4] 312850 0
Mortality - intensive care unit assessed via medical record review
Timepoint [4] 312850 0
Daily from ICU admission until ICU discharge
Secondary outcome [5] 312851 0
Mortality - hospital assessed via medical record review
Timepoint [5] 312851 0
Daily from hospital admission until hospital discharge

Eligibility
Key inclusion criteria
Patients aged 18 years or older admitted to study ICU’s who receive any crystalloid fluid resuscitation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who are transferred from another hospital to a study ICU in order to receive renal replacement therapy for acute kidney injury
2. Patients who are admitted to the ICU for consideration of organ donation.
3. Patients admitted to ICU after cardiac surgery

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)
Once the clinician decides that fluid resuscitation is needed, the sealed envelope will be opened and the treatment fluid number will be made available to the treating team.

The team will then obtain the bag of blinded study fluid with the corresponding number from a 10 litre batch of fluid with the same study number. Thereafter, all fluid resuscitation and all crystalloid fluid therapy will be performed with such blinded fluid until discharge from ICU.

If more than 10 litres of fluid are given, the patient will be allocated by the research co-ordinator to a second batch of fluid containing the same type of fluid thus maintaining blinding of treating doctors, nurses and of patient.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will be conducted using a computer-based randomisation program and sealed envelopes. A member of the research office, not involved in the study will be responsible for performing the randomisation and creating the opaque sealed envelopes.

Randomization will be in permuted blocks. Patients will be randomly assigned to one of two groups: normal saline or Plasmalyte.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
Our hypothesis is that the acid-base effects of saline are greater than Plasmalyte and that the base excess will be different between the two groups with greater metabolic acidosis (more negative base excess) with saline therapy.
Using data from previous studies, we estimate that a sample size of 27 patients in each group, will have a statistical power > 0.9 at an alpha of 0.05, if we assume a standard deviation of 2 mmol/L base-excess for each group. We plan to include 30 patients in each arm to allow for any errors in randomization or other factors that might invalidate inclusion.

Analysis will be on intention-to-treat.

Adjusted analyses will be performed using Poisson regression for binary outcomes and linear regression for continuous outcomes. Baseline covariates will include presence or absence of trauma (based on APACHE-III admission diagnosis), age, ICU admission source, APACHE-III score, and baseline serum creatinine level. Survival times will be compared using log-rank tests and presented as Kaplan-Meier curves

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/04/2015
Actual
16/06/2016
Date of last participant enrolment
Anticipated
1/04/2016
Actual
22/10/2016
Date of last data collection
Anticipated
Actual
20/12/2016
Sample size
Target
60
Accrual to date
Final
70
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3423 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 3424 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [3] 3425 0
Western Hospital - Footscray

Funding & Sponsors
Funding source category [1] 290698 0
Hospital
Name [1] 290698 0
Austin Hospital
Austin Health
Country [1] 290698 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Austin Health
145 Studley Road
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 289390 0
Individual
Name [1] 289390 0
Professor Rinaldo Bellomo
Director, Intensive Care Research
Austin Hospital
Address [1] 289390 0
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country [1] 289390 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292335 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 292335 0
Austin Health
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 292335 0
Australia
Date submitted for ethics approval [1] 292335 0
28/10/2013
Approval date [1] 292335 0
02/04/2014
Ethics approval number [1] 292335 0
HREC/13/Austin/177

Summary
Brief summary
The administration of intravenous fluid is a common intervention in acutely unwell patients. Although normal saline has been the dominant crystalloid fluid worldwide for more than century, at present, intensive care specialists in Australia and New Zealand (ANZ) broadly regard all intravenous crystalloid solutions, including normal saline and plasmalyte as equivalent. They will administer one of these two fluids for resuscitation or rehydration according to personal preference or clinical judgment in the absence of evidence that one is superior to the other in terms of clinical outcomes.

Before definitive multicenter double-blind randomized controlled trials can be performed, pilot studies are necessary to guide their optimal execution. Such pilot work makes it possible to assess the following crucial aspects of trial execution: feasibility of study design, degree of biochemical and physiological separation achieved with study interventions, safety of study approach, likely recruitment rate, likely effects, likely amounts of fluids used per patient, and power calculations.

Accordingly, we propose to perform a pilot multicenter randomized double-blind controlled trial to compare the feasibility, safety, biochemical and physiological effects of treating patients requiring fluid resuscitation with either normal saline or plasmalyte. On the basis of previous comparative data, we plan to study 60 patients (30 treated with saline vs. 30 treated with plasmalyte) and to use base excess during the first 4 days (when most of fluid administration takes place) in ICU as the primary outcome measure.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 301 301 0 0
/AnzctrAttachments/367913-hrec13austin177 (app amended))HREC Ethics Full Approval- after changes for SERP (Reviewing HREC) V3 15FEB13.pdf

Contacts
Principal investigator
Name 54710 0
Prof Rinaldo Bellomo
Address 54710 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 54710 0
Australia
Phone 54710 0
+61 3 9496 5992
Fax 54710 0
+61 3 9496 3932
Email 54710 0
[email protected]
Contact person for public queries
Name 54711 0
Glenn Eastwood
Address 54711 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 54711 0
Australia
Phone 54711 0
+61 3 9496 4835
Fax 54711 0
+61 3 9496 3932
Email 54711 0
[email protected]
Contact person for scientific queries
Name 54712 0
Rinaldo Bellomo
Address 54712 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 54712 0
Australia
Phone 54712 0
+61 3 9496 5992
Fax 54712 0
+61 3 9496 3932
Email 54712 0
[email protected]

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