ANZCTR - Registration

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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]

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

Condition category

Condition code

Other

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]

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]

Base excess as obtained from routine pathology testing and assessed via medical record review

Timepoint [1]

Daily from ICU admission until day four of ICU care.

Secondary outcome [1]

Acute kidney injury as per the RIFLE criteria as obtained from routine pathology testing and assessed via medical record review

Timepoint [1]

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]

Delta creatine (the difference between baseline and peak creatinine) as determined by medical record review

Timepoint [2]

Daily from ICU admission until ICU discharge

Secondary outcome [3]

Requirement for renal replacement therapy assessed via medical record review

Timepoint [3]

Daily from admission to ICU through to discharge from ICU

Secondary outcome [4]

Mortality - intensive care unit assessed via medical record review

Timepoint [4]

Daily from ICU admission until ICU discharge

Secondary outcome [5]

Mortality - hospital assessed via medical record review

Timepoint [5]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [2]

Barwon Health - Geelong Hospital campus - Geelong

Recruitment hospital [3]

Western Hospital - Footscray

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Austin Hospital
Austin Health

Address [1]

145 Studley Road
Heidelberg VIC 3084

Country [1]

Australia

Primary sponsor type

Hospital

Name

Austin Hospital

Address

Austin Health
145 Studley Road
Heidelberg VIC 3084

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Professor Rinaldo Bellomo
Director, Intensive Care Research
Austin Hospital

Address [1]

Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research Ethics Committee

Ethics committee address [1]

Austin Health
145 Studley Road
Heidelberg VIC 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

28/10/2013

Approval date [1]

02/04/2014

Ethics approval number [1]

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]

/AnzctrAttachments/367913-hrec13austin177 (app amended))HREC Ethics Full Approval- after changes for SERP (Reviewing HREC) V3 15FEB13.pdf

Contacts

Principal investigator

Name

Prof Rinaldo Bellomo

Address

Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9496 5992

Fax

+61 3 9496 3932

rinaldo.bellomo@austin.org.au

Contact person for public queries

Name

Glenn Eastwood

Address

Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9496 4835

Fax

+61 3 9496 3932

glenn.eastwood@austin.org.au

Contact person for scientific queries

Name

Rinaldo Bellomo

Address

Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9496 5992

Fax

+61 3 9496 3932

rinaldo.bellomo@austin.org.au

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

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Current Study Results

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Update to Study Results

Doc. No.	Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
5290	Study results article	Yes	https://doi.org/ PMID: 27604335.	Verma B, Luethi N, Cioccari L, Lloyd-Donald P, Cri... [More Details]

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