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Trial registered on ANZCTR


Registration number
ACTRN12618001622291p
Ethics application status
Not yet submitted
Date submitted
26/09/2018
Date registered
2/10/2018
Date last updated
2/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial of buffered salt solution versus 0.9% sodium chloride as fluid therapy for patients with diabetic ketoacidosis.
Scientific title
A randomised controlled trial of buffered salt solution versus 0.9% sodium chloride as fluid therapy for patients with diabetic ketoacidosis.
Secondary ID [1] 295812 0
Nil
Universal Trial Number (UTN)
U1111-1220-9417
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic ketoacidosis 309247 0
Condition category
Condition code
Metabolic and Endocrine 308123 308123 0 0
Diabetes
Metabolic and Endocrine 308638 308638 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two different types of intravenous fluid will be compared in this trial:

1. 0.9% Sodium Chloride
2. Buffered salt solution (for the purpose of this trial, the buffered salt solution that will be used is Plasma-lyte 148)

The mode of administration will be intravenous via either a peripheral intravenous cannula or a central venous catheter. The dosage will be at the discretion of the treating physician.

There will be two intervention periods of 6 months each, separated by a 1 month washout between these two periods. All participating sites will be randomised to either 0.9% saline or Plasma-lyte 148 for the first 6 month period during which all patients admitted with DKA will will be treated with the assigned fluid for the first 48 hours of ICU admission at each site. Following the first 6 month period and the 1 month washout, all sites will crossover to the other fluid for the next 6 month period.
Intervention code [1] 312142 0
Treatment: Drugs
Comparator / control treatment
The control group will receive 0.9% sodium chloride for all fluid boluses and maintenance for the first 48 hours of ICU admission.
Control group
Active

Outcomes
Primary outcome [1] 307098 0
Change in base excess on arterial blood gas from hospital admission to 48 hours post-admission or ICU discharge (whichever occurs earlier)
Timepoint [1] 307098 0
Upto 48 hours from hospital admission
Secondary outcome [1] 350683 0
ICU mortality (collected routinely by all participating ICU's as part of their reporting responsibility to Government authorities)
Timepoint [1] 350683 0
Duration of ICU admission
Secondary outcome [2] 350684 0
Hospital Mortality (collected routinely by all participating ICU's as part of their reporting responsibility to Government authorities)
Timepoint [2] 350684 0
Duration of hospital admission
Secondary outcome [3] 350685 0
Time to resolution of ketosis (routinely collected as part of usual care of patients with DKA and stored in the medical record- research co-ordinators at individual sites will transcribe this data into the trial case report form)
Timepoint [3] 350685 0
Duration of hospital admission in days (routinely collected for administrative purposes)
Secondary outcome [4] 350686 0
Cumulative insulin dosage (routinely collected as part of usual care of patients with DKA and stored in the medical record- research co-ordinators at individual sites will transcribe this data into the trial case report form)
Timepoint [4] 350686 0
48 hours post-ICU admission
Secondary outcome [5] 350687 0
Acute kidney injury as measured by rise in serum creatinine to above 1.5 times baseline serum creatinine level (routinely collected as part of usual care of patients with DKA and stored in the medical record- research co-ordinators at individual sites will transcribe this data into the trial case report form)
Timepoint [5] 350687 0
48 hours post-ICU admission
Secondary outcome [6] 350688 0
Serum sodium (routinely collected as part of usual care of patients with DKA and stored in the medical record- research co-ordinators at individual sites will transcribe this data into the trial case report form)
Timepoint [6] 350688 0
48 hours post-ICU admission
Secondary outcome [7] 352382 0
Serum potassium (routinely collected as part of usual care of patients with DKA and stored in the medical record- research co-ordinators at individual sites will transcribe this data into the trial case report form)
Timepoint [7] 352382 0
48 hrs post-ICU admission
Secondary outcome [8] 352383 0
Serum chloride (routinely collected as part of usual care of patients with DKA and stored in the medical record- research co-ordinators at individual sites will transcribe this data into the trial case report form)

- please note, this is a safety outcome for 0.9% saline- this fluid contains supraphysiological quantities of chloride and has been implicated in the development and maintenance of hyperchloraemic metabolic acidosis
Timepoint [8] 352383 0
48 hrs post-ICU admission
Secondary outcome [9] 352384 0
Serum bicarbonate (routinely collected as part of usual care of patients with DKA and stored in the medical record- research co-ordinators at individual sites will transcribe this data into the trial case report form)
Timepoint [9] 352384 0
48 hrs post-ICU admission
Secondary outcome [10] 352385 0
Serum acetoacetate (routinely collected as part of usual care of patients with DKA and stored in the medical record- research co-ordinators at individual sites will transcribe this data into the trial case report form)


- please note this is a safety outcome for the use of Plasma-lyte 148- it can theoretically provide substrate (acetate) for the generation of acetoacetate and hence may cause prolonged ketonaemia in patients with DKA
Timepoint [10] 352385 0
48 hrs post-ICU admission
Secondary outcome [11] 352386 0
serum beta-hydroxybutyrate (routinely collected as part of usual care of patients with DKA and stored in the medical record- research co-ordinators at individual sites will transcribe this data into the trial case report form)
Timepoint [11] 352386 0
48 hrs post-ICU admission

Eligibility
Key inclusion criteria
Patients greater than or equal to 16 years of age, admitted to the emergency department at participating sites with a diagnosis of diabetic ketoacidosis, which was defined as:
• Blood glucose level greater than 14 mmol/L
AND
• pH less than 7.25 OR serum bicarbonate less than 15 mmol/L
AND
• ICU admission required in the judgement of the treating clinician
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Age less than 16
• Serum potassium greater than 6.5 mmol/L prior to randomisation
• Patients with hyperosmotic hyperglycaemic, non-ketotic syndrome
• Patients who have previously been included in this 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)
This will be a cluster cross-over randomised controlled trial where the individual sites will be randomised to control or intervention for a 6 month period followed by a 1 month washout period and then crossover to the other arm for 6 months.

The allocation of individual sites will be concealed by use of an allocation schedule that will be held at an off-site location by the trial statistician, who will have to be contacted for allocations at the time of commencement of the trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation of sites using a computer-generated sequence.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Cluster crossover trial
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
All analyses will be conducted on an intention to treat basis using standard statistical methods for categorical and continuous data. The primary outcome will be analysed using t-tests and ANOVA will be used for repeated measures. Pre-defined subgroups will include Type I vs. Type II diabetes, and moderate vs. severe DKA. Other outcomes will include mortality and length of stay in hospital and ICU.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,WA
Recruitment hospital [1] 11976 0
Caboolture Hospital - Caboolture
Recruitment hospital [2] 11977 0
Cairns Base Hospital - Cairns
Recruitment hospital [3] 11978 0
Logan Hospital - Meadowbrook
Recruitment hospital [4] 11979 0
Mackay Base Hospital - Mackay
Recruitment hospital [5] 11980 0
Ipswich Hospital - Ipswich
Recruitment hospital [6] 11981 0
Rockhampton Base Hospital - Rockhampton
Recruitment hospital [7] 11982 0
Hervey Bay Hospital - Pialba
Recruitment hospital [8] 11983 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [9] 11984 0
Rockingham General Hospital - Cooloongup
Recruitment hospital [10] 11985 0
The Townsville Hospital - Douglas
Recruitment hospital [11] 11986 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [12] 12003 0
Queen Elizabeth II Jubilee Hospital - Coopers Plains
Recruitment postcode(s) [1] 24123 0
4510 - Caboolture
Recruitment postcode(s) [2] 24124 0
4870 - Cairns
Recruitment postcode(s) [3] 24125 0
4131 - Meadowbrook
Recruitment postcode(s) [4] 24126 0
4740 - Mackay
Recruitment postcode(s) [5] 24127 0
4305 - Ipswich
Recruitment postcode(s) [6] 24128 0
4700 - Rockhampton
Recruitment postcode(s) [7] 24129 0
4655 - Pialba
Recruitment postcode(s) [8] 24130 0
4575 - Birtinya
Recruitment postcode(s) [9] 24131 0
6168 - Cooloongup
Recruitment postcode(s) [10] 24132 0
4814 - Douglas
Recruitment postcode(s) [11] 24133 0
5011 - Woodville
Recruitment postcode(s) [12] 24162 0
4108 - Coopers Plains

Funding & Sponsors
Funding source category [1] 300406 0
Hospital
Name [1] 300406 0
Caboolture Hospital
Address [1] 300406 0
McKean Street
Caboolture QLD 4510
Country [1] 300406 0
Australia
Funding source category [2] 300800 0
Hospital
Name [2] 300800 0
Cairns Base Hospital
Address [2] 300800 0
165 Esplanade
Cairns North
QLD 4870
Country [2] 300800 0
Australia
Funding source category [3] 300801 0
Hospital
Name [3] 300801 0
The Townsville Hospital
Address [3] 300801 0
100 Angus Smith Drive, Douglas QLD 4814
Country [3] 300801 0
Australia
Funding source category [4] 300802 0
Hospital
Name [4] 300802 0
Mackay Base Hospital
Address [4] 300802 0
475 Bridge Rd, Mackay QLD 4740
Country [4] 300802 0
Australia
Funding source category [5] 300803 0
Hospital
Name [5] 300803 0
Rockhampton Hospital
Address [5] 300803 0
Canning St, Rockhampton City QLD 4700
Country [5] 300803 0
Australia
Funding source category [6] 300804 0
Hospital
Name [6] 300804 0
Hervey Bay Hospital
Address [6] 300804 0
Urraween Rd, Pialba QLD 4655
Country [6] 300804 0
Australia
Funding source category [7] 300805 0
Hospital
Name [7] 300805 0
Sunshine Coast University Hospital
Address [7] 300805 0
6 Doherty Street, Birtinya Qld 4575

Country [7] 300805 0
Australia
Funding source category [8] 300806 0
Hospital
Name [8] 300806 0
Logan Hospital
Address [8] 300806 0
Armstrong Rd & Loganlea Rd, Meadowbrook QLD 4131
Country [8] 300806 0
Australia
Funding source category [9] 300807 0
Hospital
Name [9] 300807 0
Ipswich Hospital
Address [9] 300807 0
Chelmsford Ave, Ipswich QLD 4305
Country [9] 300807 0
Australia
Funding source category [10] 300808 0
Hospital
Name [10] 300808 0
Queen Elizabeth II Jubilee Hospital
Address [10] 300808 0
Troughton Rd & Kessels Rd, Coopers Plains QLD 4108
Country [10] 300808 0
Australia
Funding source category [11] 300809 0
Hospital
Name [11] 300809 0
Rockhingham Hospital
Address [11] 300809 0
Elanora Dr, Cooloongup WA 6168
Country [11] 300809 0
Australia
Funding source category [12] 300810 0
Hospital
Name [12] 300810 0
The Queen Elizabeth Hospital
Address [12] 300810 0
28 Woodville Rd, Woodville South SA 5011
Country [12] 300810 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Trial Management Committee
Address
Intensive Care Unit
Wesley Hospital
Auchenflower QLD 4066
Country
Australia
Secondary sponsor category [1] 299864 0
None
Name [1] 299864 0
None
Address [1] 299864 0
None
Country [1] 299864 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 301547 0
Royal Brisbane and Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 301547 0
Human Research Ethics Office
Lower ground floor, Executive Offices
James Mayne Building
Butterfield Street
HERSTON QLD 4029
Phone: (07) 3646 5490
Ethics committee country [1] 301547 0
Australia
Date submitted for ethics approval [1] 301547 0
28/09/2018
Approval date [1] 301547 0
Ethics approval number [1] 301547 0

Summary
Brief summary
This is a cluster crossover trial to determine whether fluid therapy with a buffered salt solution (Plasmalyte-148) reduces the time to resolution of acidosis compared to 0.9% sodium chloride (saline) in critically ill patients presenting to the emergency department with diabetic ketoacidosis (DKA).

• We hypothesise that the use of PL as fluid therapy in these patients will lead to earlier resolution of acidosis and avoidance of hyperchloraemia, thereby reducing morbidity and length of stay
Trial website
nil
Trial related presentations / publications
nil
Public notes
nil

Contacts
Principal investigator
Name 86242 0
Prof Balasubramanian Venkatesh
Address 86242 0
ICU
Wesley Hospital
Auchenflower QLD 4066
Country 86242 0
Australia
Phone 86242 0
+61 7 31762111
Fax 86242 0
+61 7 32326518
Email 86242 0
bmvenkat@bigpond.net.au
Contact person for public queries
Name 86243 0
Dr Mahesh Ramanan
Address 86243 0
ICU
Caboolture Hospital
McKean Street, Caboolture QLD 4510
Country 86243 0
Australia
Phone 86243 0
+61 7 38837822
Fax 86243 0
Email 86243 0
mahesh.ramanan@health.qld.gov.au
Contact person for scientific queries
Name 86244 0
Dr Mahesh Ramanan
Address 86244 0
ICU
Caboolture Hospital
McKean Street, Caboolture QLD 4510
Country 86244 0
Australia
Phone 86244 0
+61 7 38837822
Fax 86244 0
Email 86244 0
mahesh.ramanan@health.qld.gov.au

No data has been provided for results reporting
Summary results
Not applicable