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Trial registered on ANZCTR


Registration number
ACTRN12614000289617
Ethics application status
Approved
Date submitted
7/03/2014
Date registered
19/03/2014
Date last updated
2/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A single centre nested cohort study investigating the safety and efficacy of using 0.9 % saline or Plasma-Lyte(Registered Trademark) 148 as post-operative fluid therapy in adults undergoing cardiac surgery
Scientific title
A single centre nested cohort study investigating the safety and efficacy of using 0.9 % saline or Plasma-Lyte "(Registered Trademark)" as post-operative fluid therapy in adults undergoing cardiac surgery
Secondary ID [1] 284218 0
Nil
Universal Trial Number (UTN)
U1111-1152-2216
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac Surgery 291328 0
Condition category
Condition code
Surgery 291684 291684 0 0
Other surgery
Cardiovascular 291720 291720 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is conducted as a single centre nested cohort study within the SPLIT study (0.9 % Saline versus Plasma-Lyte 148 for Intensive Care Fluid Therapy).

Patients enrolled into the SPLIT study, following cardiac surgery .During the study period the intensive care unit will be randomly assigned to a 7 week period of administration of trial fluid. There is a double crossover approach so that the each strategy is given twice.

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.
Intervention code [1] 288919 0
Treatment: Other
Comparator / control treatment
During the study period patients will receive 0.9% saline (control arm) the rate, duration, and frequency of fluid administration will determined by the treated clinician.
Control group
Active

Outcomes
Primary outcome [1] 291627 0
Chest tube output at from time of arrival to Intensive care Unit til 12 hours post operatively.
- Outcome will be recorded as the volume in chest tube at 12 hours
Timepoint [1] 291627 0
12 hours after arrival to ICU
Secondary outcome [1] 307187 0
Volume of fluid in chest drains at 24 hours
- Outcome will be recorded as the volume in chest tube at 24 hours
Timepoint [1] 307187 0
24 hours after arrival to ICU, if still in ICU
Secondary outcome [2] 307188 0
Total volume of fluid in chest drains at time of ICU discharge
- Outcome will be recorded as the volume in chest tube at time of ICU discharge
Timepoint [2] 307188 0
Assessed at time of ICU discharge or when chest tube is taken out
Secondary outcome [3] 307189 0
Proportion of patients requring a return to theatre for bleeding
Timepoint [3] 307189 0
Monitored daily throughout duration of hospital stay of each participant
Secondary outcome [4] 307190 0
Proportions of patients requiring blood products, type of blood product, and volume administered
- As recorded on patient clinical records
Timepoint [4] 307190 0
Monitored daily throughout duration of ICU stay of each participant
Secondary outcome [5] 307191 0
Total amount of study fluid given
- As recorded on patient clinical records
Timepoint [5] 307191 0
Monitored daily throughout duration of ICU stay of each participant
Secondary outcome [6] 307192 0
Daily Haemoglobin level. The haemoglobin values used will be serum heamoglobin measures taken for clinical purposes
Timepoint [6] 307192 0
Monitored daily throughout duration of ICU stay of each participant
Secondary outcome [7] 307193 0
Duration of mechanical ventilation
- As recorded on patient clinical records
Timepoint [7] 307193 0
Monitored daily throughout duration of ICU stay of each participant
Secondary outcome [8] 307194 0
Time until free from inotropes
- As recorded on patient clinical records
Timepoint [8] 307194 0
Monitored daily throughout duration of ICU stay of each participant
Secondary outcome [9] 307195 0
Daily fluid balance
- As recorded on patient clinical records
Timepoint [9] 307195 0
Monitored daily throughout duration of ICU stay of each participant
Secondary outcome [10] 307196 0
Difference between pre-operative weight and ICU discharge weight
Timepoint [10] 307196 0
Weight at time of ICU discharge
Secondary outcome [11] 307197 0
Composite outcome of major postoperative complication
- Death during hospital admisision
- Myocardial infraction
- Renal failure (requring dialysis)
- Cerebrovascular event

As recorded on medical discharge summary
Timepoint [11] 307197 0
Assessed at discharge from hospital
Secondary outcome [12] 307198 0
ICU re-admisison
Recorded as a review of patient records
Timepoint [12] 307198 0
At discharge from hospital
Secondary outcome [13] 307199 0
ICU length of stay
Timepoint [13] 307199 0
At discharge from ICU

Eligibility
Key inclusion criteria
Adult patients > 18 years
Elective or emergency cardiac surgery
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are <18 years in age
Patients who are expected to require renal replacement therapy within six hours of ICU admission
Patients who are usually on dialysis for end stage renal failure
Patients who are admitted to the ICU solely for consideration of organ donation or for palliative care
Patients previously enrolled in the SPLIT trial

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)
The ICU at Wellington Regional Hospital will be randomly assigned, in alternating seven week blocks, to use blinded 0.9% saline or Plasma- Lyte "(Registered Trademark) 148 as the default fluid.
Any patient who remains in the ICU after a crossover period will continue to receive the study fluid to which they were originally assigned up to 90 days after enrolment. As a result, no washout is required between crossover
periods.


The treatments will be administered ‘blind’ to both
investigators and patients. We will use a double crossover approach so each treatment strategy is used twice. Any patients readmitted to the ICU within the index hospital admission will continue to receive the fluid they were originally assigned to even if the unit-wide crossover has
occurred. If patients are readmitted to the ICU beyond their index hospital admission, they will not be required to receive study fluid.

The allocation of study treatments in 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.
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.
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
Crossover
Other design features
This study utilises a novel design in order to assess the relative efficacy of two standard treatment approaches. Although this study is clearly an interventional study on the basis of the Guidelines, it has many features that are more akin to an observational study than an interventional one.
Specifically, the study involves no departure from standard care and does not involve the collection of any data that are not already being collected for clinical and / or quality assurance purposes. In this study, whether or not ICU patients receive 0.9% saline or Plasma-Lyte (Registered Trademark) 148 as default therapy will be determined, on the basis of whether they are cared for in ICU.

All patients in this study will receive standard treatment except that the default therapy they receive will be randomly allocated according to the 7 week block with a double crossover .

Attending ICU specialists will have full discretion to use whichever study fluid they choose if a specific indication for one fluid or the other arises. As a result of these factors, this study involves negligible risk
Phase
Phase 4
Type of endpoint/s
Safety
Statistical methods / analysis
Currently there is a lack of established statistical methodologies for calculating sample size for cluster cross over trials with binary outcome variables. The data obtained in this study will be used to facilitate modelling of sample size requirements for a larger scale study.

There have been no studies done in this population to be able to predict an anticipated effect size of the IV fluid intervention. However, from a yet to be published pilot study of 50 patients undergoing cardiac surgery at Wellington Regional Hospital there was an estimated chest tube drainage at 24 hours or until time of ICU discharge of 706.08 mL, Standard deviation = 462.648 mL. A total sample size of 246 patient has 80% power to detect differences with a magnitude expressed as effect size of 0.36 using bilateral tests and significance level 0.05.

A complete description of the statistical analyses will be specified in a statistical analyses plan, finalised prior to completion of the study. All analyses will be conducted on an intention-to-treat basis. The primary analyses will be unadjusted analyses in which binary outcomes will be compared using relative risks with 95% confidence
intervals and chi square tests and continuous outcomes will be compared with the use of mean differences and un-paired T-tests assuming that normality assumptions are meet. If normality assumptions are not met then we plan to attempt simple data transformation, such as
a logarithm transformation, and if this fails to proceed to a Mann- Whitney rank based test. Adjusted analyses will be performed using Poisson regression for binary outcomes and linear regression for continuous outcomes. Baseline covariates will include age, gender, and specialty of admission. 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
1/04/2014
Actual
1/04/2014
Date of last participant enrolment
Anticipated
Actual
13/10/2014
Date of last data collection
Anticipated
Actual
13/10/2014
Sample size
Target
260
Accrual to date
Final
251
Recruitment outside Australia
Country [1] 5871 0
New Zealand
State/province [1] 5871 0
Wellington

Funding & Sponsors
Funding source category [1] 288843 0
Commercial sector/Industry
Name [1] 288843 0
Baxter Healthcare
Country [1] 288843 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Medical Research Institute of New Zealand
Address
Private Bag 7902, Wellington 6242
Country
New Zealand
Secondary sponsor category [1] 287536 0
None
Name [1] 287536 0
Address [1] 287536 0
Country [1] 287536 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290681 0
Multiregion Ethics Committee of the Health Research Council of New Zealand
Ethics committee address [1] 290681 0
Ethics committee country [1] 290681 0
New Zealand
Date submitted for ethics approval [1] 290681 0
Approval date [1] 290681 0
12/02/2014
Ethics approval number [1] 290681 0
14/NTB/12

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 46758 0
Dr Sumeet Reddy
Address 46758 0
Medical Research Institute of New Zealand
Private Bag 7902, Wellington 6242
Country 46758 0
New Zealand
Phone 46758 0
(+64 4 8050239)
Fax 46758 0
Email 46758 0
sumeet.reddy@mrinz.ac.nz
Contact person for public queries
Name 46759 0
Sumeet Reddy
Address 46759 0
Medical Research Institute of New Zealand
Private Bag 7902, Wellington 6242
Country 46759 0
New Zealand
Phone 46759 0
(+64 4 8050239)
Fax 46759 0
Email 46759 0
sumeet.reddy@mrinz.ac.nz
Contact person for scientific queries
Name 46760 0
Sumeet Reddy
Address 46760 0
Medical Research Institute of New Zealand
Private Bag 7902, Wellington 6242
Country 46760 0
New Zealand
Phone 46760 0
(+64 4 8050239)
Fax 46760 0
Email 46760 0
sumeet.reddy@mrinz.ac.nz

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
SourceTitleYear of PublicationDOI
Dimensions AIOverview of the study protocols and statistical analysis plan for the Saline versus Plasma-Lyte 148 for Intravenous Fluid Therapy (SPLIT) research program2015https://doi.org/10.1016/s1441-2772(23)01524-7
EmbaseEffect of 0.9% Saline or Plasma-Lyte 148 as Crystalloid Fluid Therapy in the Intensive Care Unit on Blood Product Use and Postoperative Bleeding After Cardiac Surgery.2017https://dx.doi.org/10.1053/j.jvca.2017.04.023
N.B. These documents automatically identified may not have been verified by the study sponsor.