Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001670460p
Ethics application status
Submitted, not yet approved
Date submitted
11/11/2016
Date registered
5/12/2016
Date last updated
12/11/2018
Date data sharing statement initially provided
12/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Conservative use of intravenous fluid in critically ill adults - pilot study
Scientific title
Randomised controlled feasibility study of conservative versus usual fluid management in critically ill adults
Secondary ID [1] 290525 0
None
Universal Trial Number (UTN)
U1111-1189-7486
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical illness 300945 0
Shock 300946 0
Condition category
Condition code
Other 300743 300743 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
The intervention is a conservative fluid practice guideline, regarding the use intravenous fluids in adult patients who are admitted to ICU. The intention to minimise overall fluid exposure such that patients in this group will consistently receive an amount of fluid in the lower range of usual fluid exposure in ICU. The study procedures will continue until the patient is discharged from ICU or dies..

The guideline is categorised into 5 areas: maintenance fluid, replacement of ongoing fluid losses, bolus (resuscitation) fluid, drug and other infusions, and enteral nutrition. Maintenance fluid in the intervention group will be 0.5 ml/kg/hr. Fluid resuscitation boluses will be 250 ml in the intervention group. The study will accommodate and report deviations from the guideline where this is opted into by clinicians; adherence to the guideline will otherwise be encouraged as much as possible. Replacement of fluid losses will be prescribed separately to maintenance fluid in the conservative fluid guideline group. Fluids used for drug administration will be minimised by encouraging use of any existing local instructions for this purpose but will not be mandated or altered by the study. The intervention group guideline will prompt ICU staff to consider higher caloric density enteral feeds but this will not be mandated.

The guideline will be implemented by research staff via education of ICU staff. Unit-wide education sessions will be held for registrars, residents and nursing at the commencement of the study period. Staff caring for patients who are randomised will be detailed personally by research staff and provided with the guideline. Laminated card copies of the guideline will be attached to the bed area for patients who are in the study.

The guideline was developed by the authors of the study who are senior practicing Australian ICU clinicians (medical and nursing) with scientific experience in this area. The guideline development was also informed by a survey of more than 400 ICU clinicians in Australia concerning their beliefs and usual fluid practices.

A synopsis of the fluid guideline is attached to the ANZCTR registration form.
Intervention code [1] 296376 0
Treatment: Other
Comparator / control treatment
The intervention is a USUAL fluid practice guideline, regarding the use intravenous fluids in adult patients who are admitted to ICU. The intention to expose patients to an overall amount of intravenous fluid that is typical of the mid- or upper range of normal usage. The guideline is categorised into 5 areas: maintenance fluid, replacement of ongoing fluid losses, bolus (resuscitation) fluid, drug and other infusions, and enteral nutrition.

The guideline is categorised into 5 areas: maintenance fluid, replacement of ongoing fluid losses, bolus (resuscitation) fluid, drug and other infusions, and enteral nutrition. Maintenance fluid in the usual care group will be 1 ml/kg/hr. Fluid resuscitation boluses will be 500ml in the usual care group. The study will accommodate and report deviations from the guideline where this is opted into by clinicians; adherence to the guideline will otherwise be encouraged as much as possible. There will be no advice or instructions in the usual care group in the areas of fluid loss replacement, drug administration fluid, or enteral feeds.

The guideline will be implemented by research staff via education of ICU staff. Unit-wide education sessions will be held for registrars, residents and nursing at the commencement of the study period. Staff caring for patients who are randomised will be detailed personally by research staff and provided with the guideline. Laminated card copies of the guideline will be attached to the bed area for patients who are in the study.

The guideline was developed by the authors of the study who are senior practicing Australian ICU clinicians (medical and nursing) with scientific experience in this area. The guideline development was also informed by a survey of more than 400 ICU clinicians in Australia concerning their beliefs and usual fluid practices.

A synopsis of the fluid guideline is attached to the ANZCTR registration form
Control group
Active

Outcomes
Primary outcome [1] 300159 0
Mean hourly fluid intake. This will be collected by ICU research staff who will review the daily flowsheet in the ICU.
Timepoint [1] 300159 0
From the time of randomisation until 08:00 on the morning of day 2 post-randomisation
Secondary outcome [1] 329208 0
Total fluid intake. This will be collected by ICU research staff who will review the daily flowsheet in the ICU.
Timepoint [1] 329208 0
From the time of randomisation until 08:00 on the morning of day 7 post-randomisation (or ICU discharge if earlier than day 7)
Secondary outcome [2] 329209 0
Cumulative fluid balance. This will be collected by ICU research staff who will review the daily flowsheet in the ICU.
Timepoint [2] 329209 0
From the time of randomisation until 08:00 on the morning of day 2 and day 7 post-randomisation (or ICU discharge if earlier than day 7)
Secondary outcome [3] 329212 0
Feasibility outcome - adherence to guideline: count of episodes of deviation from the fluid guideline, maintenance fluid rate. This will be collected but ICU research staff using the ICU flowsheet (medical record)
Timepoint [3] 329212 0
Until time of ICU discharge or death
Secondary outcome [4] 329213 0
Exploratory outcome: mortality. This will collected from the medical record by ICU research staff.
Timepoint [4] 329213 0
At ICU and hospital dicharge
Secondary outcome [5] 329215 0
Exploratory outcome: urine output. This will be collected by ICU research staff who will review the daily flowsheet in the ICU.
Timepoint [5] 329215 0
At ICU discharge
Secondary outcome [6] 329847 0
Cumulative fluid balance. This will be collected by ICU research staff who will review the daily flowsheet in the ICU.
Timepoint [6] 329847 0
From the time of ICU admission until 08:00 on the morning of day 2 and day 7 post-randomisation (or ICU discharge if earlier than day 7)
Secondary outcome [7] 329848 0
Median hourly fluid intake. This will be collected by ICU research staff who will review the daily flowsheet in the ICU.
Timepoint [7] 329848 0
from the time of randomisation until 08:00 on the morning of day 2 post-randomisation
Secondary outcome [8] 329849 0
Feasibility outcome - adherence to guideline: count of episodes of deviation from the fluid guideline, bolus fluid. This will be collected but ICU research staff using the ICU flowsheet (medical record)
Timepoint [8] 329849 0
until time of ICU discharge or death
Secondary outcome [9] 329850 0
Feasibility outcome - reasons for nonadherence to guideline. This will be collected as free text by ICU research staff from a convenience sample of staff
Timepoint [9] 329850 0
until time of ICU discharge or death
Secondary outcome [10] 329852 0
Exploratory outcome: ICU length of stay. This will collected from the medical record by ICU research staff.
Timepoint [10] 329852 0
until time of ICU discharge or death
Secondary outcome [11] 329853 0
Exploratory outcome: peak creatinine. This will be collected from the electronic pathology record.
Timepoint [11] 329853 0
until time of ICU discharge or death
Secondary outcome [12] 329854 0
Exploratory outcome: lowest ratio of partial pressure of oxygen in arterial blood (PaO2) to fraction of inspired oxygen (FiO2). This will be collected by ICU research staff from the medical record
Timepoint [12] 329854 0
until time of ICU discharge or death
Secondary outcome [13] 329855 0
Exploratory outcome: ventilator free hours. This will be collected from the ICU daily flowsheet.
Timepoint [13] 329855 0
until time of ICU discharge or death

Eligibility
Key inclusion criteria
1. The treating ICU team expects the patient will continue to require management in the ICU on the day after tomorrow
2. Patient has an arterial line or placement is imminent
3. Less than 12 hours since ICU admission
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age less than 18 years
2. Patient has been admitted to intensive care for treatment of burns
3. Patient has been admitted to intensive care for treatment of liver failure
4. Patient has been admitted to intensive care immediately following solid organ transplantation
5. Patient has been admitted to intensive care immediately following cardiac or lung surgery
6. Patient has been admitted to intensive care immediately following subarachnoid haemorrhage or traumatic brain injury
7. Patient has been admitted to a neurosurgical intensive care unit
8. Documented limits pertaining to end-of life management, or expectation of this in the following 48 hours
9. Women who are pregnant
10. Patients or persons responsible who are unable to read and understand the information and opt-out (English language) brochure provided for the study

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)
Allocation will be concealed by the use of the randomization module within REDCap research software.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A randomisation table will be created using computerised sequence generation by a statistician or research staff member that is independent from the study personnel
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The study will enrol 100 patients (50 in each group). Mean daily fluid intake in local practice (adult Australians in ICU) is 2.8 litres per day (SD=0.9). Assumptions are: alpha =0.05, power 90%, m = 1 (1:1 intervention: control), primary outcome is mean hourly fluid intake until the morning of day 2. The minimum clinically significant difference in mean hourly fluid intake during Stage 1 is considered to be 25ml/h. This corresponds to a minimum clinically significant difference in daily fluid intake (24h) of 600mL.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Slow development of project. Eventual impact likely to be low due to other results being published in this topic area,
Date of first participant enrolment
Anticipated
1/03/2018
Actual
Date of last participant enrolment
Anticipated
1/03/2019
Actual
Date of last data collection
Anticipated
1/04/2019
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6918 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 6919 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 6920 0
St George Hospital - Kogarah
Recruitment postcode(s) [1] 14591 0
2050 - Camperdown
Recruitment postcode(s) [2] 14592 0
2065 - St Leonards
Recruitment postcode(s) [3] 14593 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 294943 0
Charities/Societies/Foundations
Name [1] 294943 0
Intensive Care Foundation
Country [1] 294943 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The George Institute for Global Health
Address
Level 10, King George V Building
Royal Prince Alfred Hospital, Missenden Rd
Camperdown NSW 2050 Australia
Country
Australia
Secondary sponsor category [1] 293772 0
None
Name [1] 293772 0
Address [1] 293772 0
Country [1] 293772 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 296312 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 296312 0
Missenden Rd, Camperdown NSW 2050
Ethics committee country [1] 296312 0
Australia
Date submitted for ethics approval [1] 296312 0
05/11/2016
Approval date [1] 296312 0
Ethics approval number [1] 296312 0

Summary
Brief summary
The conservative fluid feasibility study is a phase II, prospective parallel-group (1:1) randomised controlled study (N=100).

The aim is to determine if a conservative fluid management strategy, compared to usual care, can achieve a clinically significant reduction in intravenous fluid intake in critically ill adults admitted to ICU for more than 48 hours.

Most general adult intensive care unit (ICU) patients who are expected to remain in ICU for more than 2 days will be eligible.

Patients in the intervention (conservative) group will receive intravenous fluid therapy according to a succinct fluid practice guideline comprising bolus fluid, maintenance fluid, replacement of lost fluid, and fluid administered with drugs or other infusions.
Patients in the control group will receive fluid in a usual way using a basic guideline.

The primary outcome is mean hourly fluid intake from the time of randomisation until the morning of day 2 after randomisation. Secondary outcomes include adherence to the fluid guidelines and fluid balance
Trial website
None
Trial related presentations / publications
Public notes
Attachments [1] 1283 1283 0 0
/AnzctrAttachments/371838-Conservative Fluid Pilot study synopsis of fluid guideline for ANZCTR 2Dec2016.pdf (Other)

Contacts
Principal investigator
Name 70410 0
A/Prof David Gattas
Address 70410 0
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 70410 0
Australia
Phone 70410 0
+61295156111
Fax 70410 0
+61295155040
Email 70410 0
[email protected]
Contact person for public queries
Name 70411 0
A/Prof David Gattas
Address 70411 0
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 70411 0
Australia
Phone 70411 0
+61295156111
Fax 70411 0
+61295155040
Email 70411 0
[email protected]
Contact person for scientific queries
Name 70412 0
A/Prof David Gattas
Address 70412 0
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 70412 0
Australia
Phone 70412 0
+61295156111
Fax 70412 0
+61295155040
Email 70412 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Study has been withdrawn (not conducted)


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
No additional documents have been identified.