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Trial registered on ANZCTR
Registration number
ACTRN12613001370796
Ethics application status
Approved
Date submitted
10/12/2013
Date registered
13/12/2013
Date last updated
6/09/2016
Type of registration
Prospectively registered
Titles & IDs
Public title
0.9% saline vs. Plasma-Lyte 148 for Intensive Care Fluid Therapy. (the SPLIT study)
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Scientific title
A multi-centre, cluster randomised, double cross over, feasibility trial investigating the effect of using 0.9% saline or Plasma-lyte 148 as fluid therapy on the risk of developing acute kidney injury in intensive care patients
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Secondary ID [1]
283744
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None
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Universal Trial Number (UTN)
U1111-1136-3741
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Trial acronym
The SPLIT study
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Intravenous Fluid Management in Critical Illness
290712
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Condition category
Condition code
Cardiovascular
291080
291080
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0
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Other cardiovascular diseases
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Anaesthesiology
291081
291081
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0
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Other anaesthesiology
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Infection
291082
291082
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0
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Other infectious diseases
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
0.9% saline for intravenous fluid therapy in intensive care. The rate, duration, and frequency of fluid administration will determined by the treated clinician. All fluid used for either fluid resuscitation or crystalloid rehydration will be 0.9% saline unless a specific indication exists for another fluid. Each of the four study ICUs will be randomly assigned, in alternating seven week blocks, to use blinded 0.9% saline or Plasma-Lyte 148 as the default resuscitation fluid. There will be no wash-out period between treatments. Each patient will receive the treatment they were assigned at the time of their ICU admission for the entire duration of their ICU admision irrespective of whether a cross-over occurs while they are admitted.
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Intervention code [1]
288431
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Treatment: Other
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Comparator / control treatment
Plasma-lyte 148 for intravenous fluid therapy in intensive care. The rate, duration, and frequency of fluid administration will determined by the treated clinician. All fluid used for either fluid resuscitation or crystalloid rehydration will be Plasma-Lyte 148 unless a specific indication exists for another fluid. Each of the four study ICUs will be randomly assigned, in alternating seven week blocks, to use blinded 0.9% saline or Plasma-Lyte 148 as the default resuscitation fluid. There will be no wash-out period between treatments. Each patient will receive the treatment they were assigned at the time of their ICU admission for the entire duration of their ICU admision irrespective of whether a cross-over occurs while they are admitted.
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Control group
Active
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Outcomes
Primary outcome [1]
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The proportion of patients with either acute kidney injury or failure based on on creatinine levels in accordance with RIFLE criteria
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Assessment method [1]
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Timepoint [1]
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Highest value measured during the patient's stay in the Intensive Care Unit (censored at day 90)
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Secondary outcome [1]
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Delta creatinine (the difference between the pre-randomisation creatinine and the peak creatinine). The creatinine values used will be serum creatinine measures taken for clinical purposes.
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Assessment method [1]
305947
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Timepoint [1]
305947
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The baseline creatinine will be the creatinine measured at study enrolment. The peak creatinine will be the highest creatinine measured in the Intensive Care Unit (censored at day 90). The creatinine values used will be serum creatinine measures taken for clinical purposes.
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Secondary outcome [2]
305948
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the cumulative incidence of acute kidney injury by category based on creatinine levels and classified into the following groups: Risk, Injury, Failure, Loss, and End stage renal failure. The creatinine values used will be serum creatinine measures taken for clinical purposes.
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Assessment method [2]
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Timepoint [2]
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based on the highest value measured during the patient's stay in the Intensive Care Unit (censored at day 90)
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Secondary outcome [3]
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proportion of patients requiring renal replacement therapy
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Assessment method [3]
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Timepoint [3]
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during the course of their ICU admission
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Secondary outcome [4]
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proportion of patients requiring renal replacement therapy (among those patients who require renal replacement therapy in the Intensive Care Unit)
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Assessment method [4]
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Timepoint [4]
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after hospital discharge
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Secondary outcome [5]
305951
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proportion of patients requiring mechanical ventilation
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Assessment method [5]
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Timepoint [5]
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during the course of their ICU admission
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Secondary outcome [6]
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duration of mechanical ventilation (among patients who require mechanical ventilation)
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Assessment method [6]
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Timepoint [6]
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during the course of their ICU admission
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Secondary outcome [7]
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Length of ICU admission (days)
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Assessment method [7]
305953
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Timepoint [7]
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Time from enrolment until ICU discharge
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Secondary outcome [8]
305956
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Length of hospital admission (days)
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Assessment method [8]
305956
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Timepoint [8]
305956
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time from enrolment until hospital discharge
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Secondary outcome [9]
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proportion of patients who require readmission to ICU
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Assessment method [9]
305957
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Timepoint [9]
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within their index hospital admission
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Secondary outcome [10]
308113
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the cumulative incidence of acute kidney injury by KDIGO stage category based on creatinine levels and classified into the following groups: KDIGO stage 1, KDIGO stage 2, and KDIGO stage 3. The creatinine values used will be serum creatinine measures taken for clinical purposes.
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Assessment method [10]
308113
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Timepoint [10]
308113
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based on the highest serum creatinine value measured during the patient's stay in the Intensive Care Unit (censored at day 90)
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Eligibility
Key inclusion criteria
Patients admitted to the study ICU who require crystalloid fluid therapy
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Minimum age
No limit
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. patients currently receiving or expected to require renal replacement therapy within six hours of ICU admission 2. patients who are usually on dialysis for end stage renal failure 3. patients who are admitted to the ICU solely for consideration of organ donation or for palliative care 4. patients previously enrolled in the SPLIT study
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The study is a cluster cross over trial in which the entire ICU will be randomly assigned to using either 0.9% saline or plasma-lyte 148 for routine fluid therapy. Each of four study ICUs will use each treatment strategy twice over the 28 weeks of the study. The allocation of study treatments in each cluster will be determined ahead of time by the study statistician. Masked study fluid appropriate for each study block which is labelled either 'fluid A' or 'fluid B' will be delivered to each study unit by Baxter Pty Ltd (who will prepare blinded study fluids for this study). Allocation concealment will be maintained until all analyses (including post hoc analyses) are complete.
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The order of study treatments will be determined at random by the study statistician using a computer algorithm.
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Masking / blinding
Blinded (masking used)
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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
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Intervention assignment
Crossover
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Other design features
Multicentre, cluster, double cross over.
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Phase
Phase 3
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Type of endpoint/s
Efficacy
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Statistical methods / analysis
Analyses will be conducted on an intention-to-treat basis. Primary and secondary outcomes will be analysed using longitudinal analysis techniques accounting for attending hospital and drug sequence. Binomial outcomes will be assessed using generalized estimating equations (GEE) with results reported as Odds Ratios (95%CI) while continuous outcomes will be analysed using generalised linear modelling (GLM) and reported as either differences (95%CI) or ratios (95%CI) as appropriate. Sensitivity analysis will be performed adjusting for an a-priori defined list of covariates (presence or absence of trauma, APACHE-III admission diagnosis, age, ICU admission source, APACHE-II score, and baseline serum creatinine level) with results reported both overall and at an individual hospital level. All analysis will be performed using SAS version 9.3 (SAS Institute Inc., Cary, USA) and a two-sided p-value of 0.05 will be considered to be statistically significant.
Due to the current lack of established statistical methodologies for calculating sample size for cluster cross over trials with binary outcome variables, we have not performed any sample size calculations for this study. However, the data obtained in this study will be used to facilitate modelling of sample size requirements for a larger scale study. This study will enrol between 2,000 and 3,000 patients over a 28-week period and will be the largest prospective clinical trial comparing 0.9% saline to plasma-lyte 148 ever conducted.
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Recruitment
Recruitment status
Completed
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Date of first participant enrolment
Anticipated
15/03/2014
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Actual
1/04/2014
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Date of last participant enrolment
Anticipated
14/10/2014
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Actual
14/10/2014
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Date of last data collection
Anticipated
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Actual
5/01/2016
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Sample size
Target
2500
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Accrual to date
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Final
2262
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Recruitment outside Australia
Country [1]
5672
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New Zealand
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State/province [1]
5672
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Auckland, Wellington, and Christchurch
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Funding & Sponsors
Funding source category [1]
288414
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Government body
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Name [1]
288414
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Health Research Council of New Zealand
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Address [1]
288414
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PO Box 5541, Wellesley Street, Auckland 1141
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Country [1]
288414
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New Zealand
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Funding source category [2]
288415
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Commercial sector/Industry
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Name [2]
288415
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Baxter Pty Ltd
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Address [2]
288415
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Baxter Dr, Old Toongabbie NSW 2146, Australia
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Country [2]
288415
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Australia
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Primary sponsor type
Charities/Societies/Foundations
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Name
Medical Research Institute of New Zealand
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Address
Private Bag 7902
Wellington 6242
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Country
New Zealand
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Secondary sponsor category [1]
287122
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None
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Name [1]
287122
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Address [1]
287122
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Country [1]
287122
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Other collaborator category [1]
277723
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Hospital
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Name [1]
277723
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Capital Coast District Health Board
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Address [1]
277723
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Private Bag 7902
Wellington South 6242
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Country [1]
277723
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New Zealand
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Other collaborator category [2]
277724
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Hospital
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Name [2]
277724
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Canterbury District Health Board
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Address [2]
277724
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Private Bag 4710
Christchurch 8104
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Country [2]
277724
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New Zealand
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Other collaborator category [3]
277725
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Hospital
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Name [3]
277725
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Auckland District Health Board
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Address [3]
277725
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Private Bag 92024
Auckland Mail Centre
Auckland 1142
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Country [3]
277725
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New Zealand
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
290294
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Northern B Health and Disability Ethics Committee
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Ethics committee address [1]
290294
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Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6011
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Ethics committee country [1]
290294
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New Zealand
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Date submitted for ethics approval [1]
290294
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Approval date [1]
290294
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10/12/2013
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Ethics approval number [1]
290294
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12NTB57
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Summary
Brief summary
The administration of intravenous fluid is a common therapy in acutely unwell patients. The study will provide preliminary data from a large interventional trial to inform clinicians looking after acutely unwell patients as to whether 0.9% saline or Plasma-Lyte 148 'Registered Trademark' is the preferred fluid for routine use in the ICU.
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Trial website
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Trial related presentations / publications
Manuscript published. Young P, Bailey M, Beasley R, Henderson S, Mackle D, McArthur C, McGuinness S,
Mehrtens J, Myburgh J, Psirides A, Reddy S, Bellomo R; SPLIT Investigators;
ANZICS CTG. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney
Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical
Trial. JAMA. 2015 Oct 27;314(16):1701-10. doi: 10.1001/jama.2015.12334. Erratum
in: JAMA. 2015 Dec 15;314(23):2570.
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Public notes
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Contacts
Principal investigator
Name
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Dr Paul Young
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Address
44898
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c/o Intensive Care Unit
Wellington Hospital
Private Bag 7902
Newtown
Wellington 6242
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Country
44898
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New Zealand
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Phone
44898
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+6448060441
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Fax
44898
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Email
44898
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[email protected]
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Contact person for public queries
Name
44899
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Ms Diane Mackle
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Address
44899
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Medical Research Institute of New Zealand
Private Bag 7902
Wellington 6242
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Country
44899
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New Zealand
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Phone
44899
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+64 4 805 0147
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Fax
44899
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Email
44899
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[email protected]
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Contact person for scientific queries
Name
44900
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Ms Diane Mackle
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Address
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Medical Research Institute of New Zealand
Private Bag 7902
Wellington 6242
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Country
44900
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New Zealand
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Phone
44900
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+64 4 805 0147
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Fax
44900
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Email
44900
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[email protected]
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No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Documents added manually
No documents have been uploaded by study researchers.
Documents added automatically
Source
Title
Year of Publication
DOI
Embase
Balanced crystalloids versus normal saline as intravenous fluid therapy among critically ill patients: A meta-analysis of randomized controlled trials.
2019
Embase
Sepsis Resuscitation: Fluid Choice and Dose.
2016
https://dx.doi.org/10.1016/j.ccm.2016.01.007
Embase
Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: The SPLIT randomized clinical trial.
2015
https://dx.doi.org/10.1001/jama.2015.12334
Dimensions AI
Overview of the study protocols and statistical analysis plan for the Saline versus Plasma-Lyte 148 for Intravenous Fluid Therapy (SPLIT) research program
2015
https://doi.org/10.1016/s1441-2772(23)01524-7
N.B. These documents automatically identified may not have been verified by the study sponsor.
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