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Trial registered on ANZCTR


Registration number
ACTRN12614000269639
Ethics application status
Approved
Date submitted
7/03/2014
Date registered
13/03/2014
Date last updated
11/02/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A single centre nested cohort study investigating the effect of using 0.9 % saline or Plasmalyte 148 as primary fluid therapy on gastrointestinal complications in mechanically ventilated patients with nasogastric enteral nutrition
Scientific title
A single centre nested cohort study investigating the effect of using 0.9 % saline or Plasmalyte 148 as primary fluid therapy on gastrointestinal complications in mechanically ventilated patients with nasogastric enteral nutrition
Secondary ID [1] 284216 0
Nil
Universal Trial Number (UTN)
U1111-1152-4609
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical Illness 291324 0
Mechanical Ventilation 291325 0
Condition category
Condition code
Oral and Gastrointestinal 291681 291681 0 0
Normal oral and gastrointestinal development and function
Diet and Nutrition 291682 291682 0 0
Other diet and nutrition disorders

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 (Registered Trademark) 148 for Intensive Care Fluid Therapy).

Intervention = Plasma-Lyte (Registered Trademark) 148, this will be given at intravenously at the discretion of the treating clinician during the ICU stay.

Fluid will be given in alternating seven week blocks. 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 cross-over periods. The treatments will be administered ‘blind’ to both investigators and patients.

Patients enrolled into the SPLIT study, expected to be mechanically ventilated for longer than 48 hours, and receiving enteral nutrition via nasogastric tube will be eligible for this pilot study.

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.
Intervention code [1] 288916 0
Treatment: Other
Comparator / control treatment
During the study period patients will receive 0.9% saline (control arm) solution. These will be given intravenously at the discretion of the treating clinician.
Control group
Active

Outcomes
Primary outcome [1] 291623 0
Composite outcome of proportion of patients with gastrointestinal complications :
High gastric residual volume (Gastric residual volume > 500 ml)
Patients with vomiting
Patients with diarrhoea
Method to assess outcome- review from patients clinical records.
Timepoint [1] 291623 0
Monitored daily throughout duration of mechanical ventilation of each participant
Secondary outcome [1] 307177 0
Diet volume ratio (volume received/ volume prescribed)
Timepoint [1] 307177 0
At 48 hours after commencement of nasogastric feeding
Secondary outcome [2] 307178 0
Duration of nasogastric (NG) enteral feeding
Method to assess outcome - Review of patient records
Timepoint [2] 307178 0
Monitored daily throughout duration of ICU stay of each participant
Secondary outcome [3] 307179 0
Cause of NG enteral feeding finalization
Method to assess outcome - Review of patient records
Timepoint [3] 307179 0
Monitored daily throughout duration of ICU stay of each participant
Secondary outcome [4] 307180 0
Days of mechanical ventilation
Method to assess outcome - Review of patient records
Timepoint [4] 307180 0
Monitored daily throughout duration of ICU stay of each participant
Secondary outcome [5] 307181 0
ICU length of stay
Timepoint [5] 307181 0
At discharge from ICU
Secondary outcome [6] 307182 0
ICU re-admission
Method of assess outcome - review of patient records
Timepoint [6] 307182 0
At discharge from hospital
Secondary outcome [7] 307183 0
Hospital length of stay
Timepoint [7] 307183 0
At discharge from hospital
Secondary outcome [8] 307184 0
In-Hospital mortality
Timepoint [8] 307184 0
Duration of Hospital stay

Eligibility
Key inclusion criteria
Adult patients > 18 years.

Patients who are expected to be mechanically ventilated for greater than 48 hours and receiving NG enteral nutrition.
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 expected to require mechanical ventilation for less than 48 hours.
Patients mechanically ventilated and not receiving enteral nutrition.
Patients receiving duodenal or jejunal feeding.
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 cross-over 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 in which they are admitted to the study hospital. There will be a double crossover design, so each intervention is used twice.

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
Due to the current lack of established statistical methodologies for calculating sample size for cluster cross over trials with binary outcome variables we are not able to do a power calculation. 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. The development of GI complications in mechanically ventilated patients as defined by our criteria has been reported at 50 – 60% in literature.

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
Active, not recruiting
Date of first participant enrolment
Anticipated
1/04/2014
Actual
5/04/2014
Date of last participant enrolment
Anticipated
Actual
11/10/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment outside Australia
Country [1] 5869 0
New Zealand
State/province [1] 5869 0
Wellington

Funding & Sponsors
Funding source category [1] 288839 0
Commercial sector/Industry
Name [1] 288839 0
Baxter Healthcare
Country [1] 288839 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Medical Research Institute of New Zealand
Address
Private Bag 7902, Wellington 6242
New Zealand
Country
New Zealand
Secondary sponsor category [1] 287533 0
None
Name [1] 287533 0
Address [1] 287533 0
Country [1] 287533 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290679 0
Multiregion Ethics Committee of the Health Research Council of New Zealand
Ethics committee address [1] 290679 0
c/- Ministry of Health
PO Box 5013
1 The Terrace
Wellington 6011
Ethics committee country [1] 290679 0
New Zealand
Date submitted for ethics approval [1] 290679 0
Approval date [1] 290679 0
12/02/2014
Ethics approval number [1] 290679 0
14/NTB/10

Summary
Brief summary
0.9% saline has been used in clinical practice for fluid resuscitation and general fluid therapy since the 1880s. While it is the most commonly used IV resuscitation fluid in the world, some data raise the possibility that using 0.9% saline for intravenous therapy may be related to altered gastrointestinal (GI) function .Current data are insufficient to recommend clinical practice change and further data from an interventional trial are urgently needed. However, the design of such a Trial requires sufficient pilot data to establish feasibility, safety, power calculations, and define an optimal study protocol.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 46750 0
Dr Sumeet Reddy
Address 46750 0
Medical Research Institute of New Zealand
Private Bag 7902, Wellington 6242
New Zealand
Country 46750 0
New Zealand
Phone 46750 0
+64 4 805 0245
Fax 46750 0
Email 46750 0
sumeet.reddy@mrinz.ac.nz
Contact person for public queries
Name 46751 0
Dr Sumeet Reddy
Address 46751 0
Medical Research Institute of New Zealand
Private Bag 7902, Wellington 6242
New Zealand
Country 46751 0
New Zealand
Phone 46751 0
+64 4 805 0245
Fax 46751 0
Email 46751 0
sumeet.reddy@mrinz.ac.nz
Contact person for scientific queries
Name 46752 0
Dr Sumeet Reddy
Address 46752 0
Medical Research Institute of New Zealand
Private Bag 7902, Wellington 6242
New Zealand
Country 46752 0
New Zealand
Phone 46752 0
+64 4 805 0245
Fax 46752 0
Email 46752 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
N.B. These documents automatically identified may not have been verified by the study sponsor.