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Balanced Multi-Electrolyte Solution Versus Saline Trial for Diabetic KetoAcidosis (BEST-DKA)

Primary Purpose

Diabetic Ketoacidosis

Status
Not yet recruiting
Phase
Phase 3
Locations
Australia
Study Type
Interventional
Intervention
Plasma-Lyte 148
0.9% sodium chloride
Sponsored by
The George Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Ketoacidosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients in the ED with a primary diagnosis of moderate to severe DKA for whom both saline and Plasma-Lyte® 148 are considered appropriate fluids Blood glucose level > 14mmol/L pH < 7.25 Serum bicarbonate <15 mmol/L Elevated anion gap > 12mEq/L Ketones positive on finger prick measurements In the judgement of the treating clinician critical care area admission is required Exclusion Criteria: Age less than 18 years Patients who have received more than 2000ml of non study fluid prior to study enrolment Serum Na > 155 or <120 mmol/L Contraindication to either study fluid e.g. previous allergic reaction to Plasma-Lyte® 148 Patients with hyperosmotic hyperglycaemic non-ketotic syndrome Other clinical conditions that preclude large volumes of fluid resuscitation Previous inclusion in BEST-DKA trial

Sites / Locations

  • Royal North Shore Hospital
  • Redcliffe Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Plasma-Lyte® 148

0.9% sodium chloride

Arm Description

Plasma-Lyte® 148 fluid 1L given intravenously for fluid replacement

Normal saline fluid 1L given intravenously for fluid replacement

Outcomes

Primary Outcome Measures

Hospital free days (HFD) up to day-28 after study enrolment
Number of hospital free days from time of hospital discharge

Secondary Outcome Measures

ICU free days up to 28 days after study enrolment
Number of ICU free days from time of ICU discharge
ICU and hospital readmissions up to 28 days after study enrolment
Number of days free from ICU and hospital from time of hospital discharge
Acute kidney injury assessed by comparing serum creatinine using Kidney Disease: Improving Global Outcomes (KDIGO) criteria
injury assessed by comparing change in serum creatinine using Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Episodes of post-study enrolment decrease in Glasgow Coma Scale (GCS) by more than 2 in the first 24 hours
decrease in Glasgow Coma Score by more than 2 points
Time to resolution of ketosis
resolution of acidosis
Cumulative insulin dosage in the first 48 hours
Total amount of insulin given to the patient from enrolment to 48 hours
Duration of IV insulin infusion
Total amount of IV insulin given to the patient from time of enrolment to day 28
Cumulative potassium replacement
Total amount of potassium given to the patient from time of enrolment to day 28

Full Information

First Posted
February 7, 2023
Last Updated
February 28, 2023
Sponsor
The George Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05752279
Brief Title
Balanced Multi-Electrolyte Solution Versus Saline Trial for Diabetic KetoAcidosis
Acronym
BEST-DKA
Official Title
Balanced Multi-electrolyte Solution Versus 0.9% Sodium Chloride as Fluid Therapy for Patients Presenting With Moderate to Severe Diabetic Ketoacidosis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 2023 (Anticipated)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The George Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this blinded, cluster cross-over, randomised controlled trial is to determine whether fluid therapy with Plasma-Lyte® 148 increases the number of days alive and days out of hospital to day-28 compared to 0.9% sodium chloride ('0.9% saline') in critically ill patients presenting to the Emergency Department (ED) and deemed to require admission to a critical care area (ICU, HDU) with moderate to severe diabetic ketoacidosis (DKA).
Detailed Description
DKA is a life-threatening complication of diabetes mellitus, described in patients with both type-1 diabetes, and type-2 diabetes(1). Data from the Australian Institute of Health and Welfare suggest that between 2009-10 to 2014-15, there has been a 21% increase in the hospitalisation amongst young people with DKA(2). An interrogation of the Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcomes Research (CORE) database revealed that the incidence of ICU admission of patients with DKA in Australia and New Zealand increased 5-fold between 2000 and 2013 (0.97/100000, 95%CI 0.84 to1.10) in 2000 to (5.3/100000, 95%CI 4.98to 5.53, (P<0.0001)(3). Increasing incidences were observed predominantly in rural and metropolitan hospitals (Figure 1), about 88% of the admissions to the ICU were from the ED. The median (IQR) ICU and hospital length of stay were 1.8 (1-2.8) and 4 (2.6-7.4) days respectively. Recent data from the ANZICS-CORE database confirmed the persistent high admission rate of severe DKA to Australian ICUs - 2849 and 2862 admissions in 2019 and 2020. A major review of DKA management protocols in 2017 concluded that there are major deficiencies in evidence for optimal management of DKA(33). Current practice is guided by weak evidence and consensus opinion. Studies comparing Plasma-Lyte® 148 vs. 0.9% saline in DKA demonstrate a trend towards a more rapid resolution of acidosis, equivalent glucose control and stable ketones with Plasma-Lyte® 148. In addition, there are trends towards reduced length of ICU and hospital stay with the use of Plasma-Lyte® 148. Given the clinical uncertainty and substantial variability in practice. there is a scientific, clinical and health economic imperative to conduct a high-fidelity study to provide definitive evidence to inform clinicians regarding the choice of resuscitation fluids for patients with DKA. BEST-DKA will address this critical knowledge gap. BEST-DKA is a multi-centre, blinded, cluster-crossover trial conducted in 20 Australian hospitals, consisting of two 12-month intervention periods with a one-month inter-period gap. Each hospital is a single cluster, with all patients admitted with DKA to that hospital's ED during the intervention periods will potentially be eligible for inclusion in the trial. After the first 12-month intervention period during which recruited patients will receive either Plasma-Lyte® 148 or 0.9% saline, there will be a one-month inter-period gap during which patients will not be recruited into the trial. Following this each critical care area will change to using the fluid to which they were not assigned for the first period (Figure 4). All included patients will receive blinded fluids (Plasma-Lyte® 148 or 0.9% saline) as part of their DKA therapy depending on the fluid assigned to the site for the relevant intervention period. Both study fluids are manufactured by Baxter Healthcare Pty Ltd (Old Toongabbie, NSW) and will be labelled, packed and distributed by the company directly to the study sites in periodic shipments. Study fluid will be coded and labelled in compliance with applicable regulations, and in a manner that protects the blinding. All clinicians involved in the prescription of blinded study treatment must read Product Information for both Plasma-Lyte® 148 and 0.9% saline which provide detailed information about the composition, indications, side effects, suggested dosage and contraindications of the study treatments. The volume and rate of blinded study fluid administered will be guided by the standard clinical endpoints determined by the treating clinician. Study treatments will be started following study enrolment and continue until discharge from a critical care area or for a maximum of 72 hrs, whichever is earlier. If patients are re-admitted to the critical care area within 72 hours with a relapse of ketoacidosis, the clinician may use open label fluids for the managements of ketoacidosis. within 72 hours they will continue to receive blinded treatment fluid. Glucose containing solutions can be added in as required for blood glucose or ketosis management. The use of bicarbonate therapy and the need for potassium, phosphate and magnesium supplementation will be at the discretion of the treating clinician and data on its use will be collected. The primary outcome will be evaluated at day-28 and patients contacted via telephone. End-user/consumer representatives have been involved in all components of the research program including protocol development, choice of primary outcome, funding applications, and membership of the management committee. End-user/consumer representatives will continue to be involved in the conduct of the study and play a key role in the dissemination of results. Currently, membership of the study management committee includes the President of the advocacy group, Diabetes Australia; Director of Australian Centre for Accelerating Diabetes Innovations (ACADI); and a consumer who lives with diabetes. This study aligns with the Medical Research Future Fund (Australia Government grant) funded ACADI objective to address the acute complications of diabetes including management of DKA. The study has been endorsed by the Australasian College for Emergency Medicine (ACEM) and a letter of support from for the study from Diabetes Australia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Ketoacidosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
680 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Plasma-Lyte® 148
Arm Type
Active Comparator
Arm Description
Plasma-Lyte® 148 fluid 1L given intravenously for fluid replacement
Arm Title
0.9% sodium chloride
Arm Type
Active Comparator
Arm Description
Normal saline fluid 1L given intravenously for fluid replacement
Intervention Type
Drug
Intervention Name(s)
Plasma-Lyte 148
Other Intervention Name(s)
Balanced multi-electrolyte solution
Intervention Description
Plasma-Lyte® 148 intravenous fluid for resuscitation in patients with keto-acidosis
Intervention Type
Drug
Intervention Name(s)
0.9% sodium chloride
Other Intervention Name(s)
normal saline
Intervention Description
0.9% sodium chloride intravenous fluid for resuscitation in patients with keto-acidosis
Primary Outcome Measure Information:
Title
Hospital free days (HFD) up to day-28 after study enrolment
Description
Number of hospital free days from time of hospital discharge
Time Frame
from time of enrolment to 28 days
Secondary Outcome Measure Information:
Title
ICU free days up to 28 days after study enrolment
Description
Number of ICU free days from time of ICU discharge
Time Frame
28 days after enrolment
Title
ICU and hospital readmissions up to 28 days after study enrolment
Description
Number of days free from ICU and hospital from time of hospital discharge
Time Frame
28 days after enrolment
Title
Acute kidney injury assessed by comparing serum creatinine using Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Description
injury assessed by comparing change in serum creatinine using Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Time Frame
28 days after enrolment
Title
Episodes of post-study enrolment decrease in Glasgow Coma Scale (GCS) by more than 2 in the first 24 hours
Description
decrease in Glasgow Coma Score by more than 2 points
Time Frame
first 24 hours from enrolment
Title
Time to resolution of ketosis
Description
resolution of acidosis
Time Frame
from time of enrolment to day 28
Title
Cumulative insulin dosage in the first 48 hours
Description
Total amount of insulin given to the patient from enrolment to 48 hours
Time Frame
first 48 hours from time of enrolment
Title
Duration of IV insulin infusion
Description
Total amount of IV insulin given to the patient from time of enrolment to day 28
Time Frame
from time of enrolment to day 28
Title
Cumulative potassium replacement
Description
Total amount of potassium given to the patient from time of enrolment to day 28
Time Frame
from time of enrolment to day 28
Other Pre-specified Outcome Measures:
Title
Cost-effectiveness
Description
Calculation of the incremental cost-effectiveness ratios
Time Frame
from time of enrolment to day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients in the ED with a primary diagnosis of moderate to severe DKA for whom both saline and Plasma-Lyte® 148 are considered appropriate fluids Blood glucose level > 14mmol/L pH < 7.25 Serum bicarbonate <15 mmol/L Elevated anion gap > 12mEq/L Ketones positive on finger prick measurements In the judgement of the treating clinician critical care area admission is required Exclusion Criteria: Age less than 18 years Patients who have received more than 2000ml of non study fluid prior to study enrolment Serum Na > 155 or <120 mmol/L Contraindication to either study fluid e.g. previous allergic reaction to Plasma-Lyte® 148 Patients with hyperosmotic hyperglycaemic non-ketotic syndrome Other clinical conditions that preclude large volumes of fluid resuscitation Previous inclusion in BEST-DKA trial
Facility Information:
Facility Name
Royal North Shore Hospital
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anthony Delaney
Facility Name
Redcliffe Hospital
City
Redcliffe
State/Province
Queensland
ZIP/Postal Code
4020
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Balanced Multi-Electrolyte Solution Versus Saline Trial for Diabetic KetoAcidosis

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