Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001622291
Ethics application status
Approved
Date submitted
26/09/2018
Date registered
2/10/2018
Date last updated
4/08/2022
Date data sharing statement initially provided
15/11/2019
Date results information initially provided
16/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Sodium Chloride Or Plasmalyte Evaluation for patients with Diabetic
KetoAcidosis (SCOPE-DKA)
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
Sex
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
Continuous variables will be assessed for parametricity and reported as mean?±?standard deviation (SD) or median and interquartile range (IQR). Categorical variables will be reported as frequencies and proportions. Feasibility will be evaluated with descriptive, summary statistics. For clinical outcomes, comparisons between the NS and PL groups will be performed using the Mann-Whitney U test for continuous variables and the Fisher exact test for categorical variables. To adjust for cluster-level correlation, generalized, linear mixed models will be used with fixed effects (group allocation) and site as a random effect with patients nested within sites. Differences between groups will be reported as odds ratio (OR) with 95% confidence intervals. P values will be reported but there will be no threshold for statistical significance given this trial was not powered to specifically investigate differences in any of the clinical outcomes between groups. Pre-specified sensitivity analyses will be performed using two alternate definitions for the primary outcome: 1) resolution of diabetic ketoacidosis at 24 hours AND 2) resolution of diabetic ketoacidosis according to the American Diabetes Association.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/02/2019
Actual
2/09/2019
Date of last participant enrolment
Anticipated
30/09/2020
Actual
30/09/2020
Date of last data collection
Anticipated
28/02/2021
Actual
31/01/2021
Sample size
Target
100
Accrual to date
Final
93
Recruitment in Australia
Recruitment state(s)
QLD,SA,WA
Recruitment hospital [1] 11976 0
Caboolture Hospital - Caboolture
Recruitment hospital [2] 11979 0
Mackay Base Hospital - Mackay
Recruitment hospital [3] 11980 0
Ipswich Hospital - Ipswich
Recruitment hospital [4] 11981 0
Rockhampton Base Hospital - Rockhampton
Recruitment hospital [5] 11982 0
Hervey Bay Hospital - Pialba
Recruitment hospital [6] 11983 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [7] 12003 0
Queen Elizabeth II Jubilee Hospital - Coopers Plains
Recruitment postcode(s) [1] 24123 0
4510 - Caboolture
Recruitment postcode(s) [2] 24126 0
4740 - Mackay
Recruitment postcode(s) [3] 24127 0
4305 - Ipswich
Recruitment postcode(s) [4] 24128 0
4700 - Rockhampton
Recruitment postcode(s) [5] 24129 0
4655 - Pialba
Recruitment postcode(s) [6] 24130 0
4575 - Birtinya
Recruitment postcode(s) [7] 24162 0
4108 - Coopers Plains

Funding & Sponsors
Funding source category [1] 300406 0
Hospital
Name [1] 300406 0
Caboolture Hospital
Country [1] 300406 0
Australia
Funding source category [2] 300800 0
Hospital
Name [2] 300800 0
Cairns Base Hospital
Country [2] 300800 0
Australia
Funding source category [3] 300801 0
Hospital
Name [3] 300801 0
The Townsville Hospital
Country [3] 300801 0
Australia
Funding source category [4] 300802 0
Hospital
Name [4] 300802 0
Mackay Base Hospital
Country [4] 300802 0
Australia
Funding source category [5] 300803 0
Hospital
Name [5] 300803 0
Rockhampton Hospital
Country [5] 300803 0
Australia
Funding source category [6] 300804 0
Hospital
Name [6] 300804 0
Hervey Bay Hospital
Country [6] 300804 0
Australia
Funding source category [7] 300805 0
Hospital
Name [7] 300805 0
Sunshine Coast University Hospital
Country [7] 300805 0
Australia
Funding source category [8] 300806 0
Hospital
Name [8] 300806 0
Logan Hospital
Country [8] 300806 0
Australia
Funding source category [9] 300807 0
Hospital
Name [9] 300807 0
Ipswich Hospital
Country [9] 300807 0
Australia
Funding source category [10] 300808 0
Hospital
Name [10] 300808 0
Queen Elizabeth II Jubilee Hospital
Country [10] 300808 0
Australia
Funding source category [11] 300809 0
Hospital
Name [11] 300809 0
Rockhingham Hospital
Country [11] 300809 0
Australia
Funding source category [12] 300810 0
Hospital
Name [12] 300810 0
The Queen Elizabeth Hospital
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
Approved
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
03/12/2018
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
[email protected]
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
[email protected]
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
[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
IPD sharing was not part of the ethics approval.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Ramanan M, Attokaran A, Murray L, et al. Sodium ch... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseSodium chloride or Plasmalyte-148 evaluation in severe diabetic ketoacidosis (SCOPE-DKA): a cluster, crossover, randomized, controlled trial.2021https://dx.doi.org/10.1007/s00134-021-06480-5
N.B. These documents automatically identified may not have been verified by the study sponsor.