Intravenous Fluids in Adults With Diabetic Ketoacidosis in the Emergency Department

NCT04926740 | Completed Results

• 1 other identifier: 119430
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetes mellitus is a common chronic disease. It is estimated that up to 40% of adults may develop diabetes in their lifetime. Patients with poorly controlled blood sugars often visit the emergency department for treatment of potentially dangerous and life-threatening complications of diabetes, including "diabetic ketoacidosis" (DKA), a condition where the body does not have enough insulin or cannot effectively use the insulin that is produced. As a result, the body produces a chemical called "ketones" as another source of energy, which increase the acid levels of blood and impairs organ function throughout the body. In the emergency department, patients with DKA are usually treated with insulin and large amounts of intravenous fluid. Recent research suggests the fluid type used may be important in treating DKA. Normal saline (0.9% sodium chloride) is the most commonly used intravenous fluid in treating DKA, but it has a very high concentration of chloride and can lead to additional acid production when given in large volumes. Ringer's lactate is another type of intravenous fluid that more closely matches the chemistry of fluid in our bodies and in theory, does not increase the acidity of blood. While there may be benefits to giving Ringer's lactate instead of normal saline, past studies have included very few patients and thus, definite recommendations on preferred fluid type still cannot be made. This study's research question is: In adults with DKA, does giving Ringer's Lactate result in faster resolution of DKA compared to normal saline? The investigators hypothesize that patients who are given Ringer's Lactate will have faster resolution of DKA. If the hypothesis is correct, results will provide scientific proof that current diabetic ketoacidosis guidelines should change with respect to fluid choice. In this study, patients with DKA presenting to the emergency department will be randomly assigned to receive either normal saline or Ringer's Lactate. As this is an exploratory (pilot) study, the main goal is to ensure that a larger study will be practical and feasible on a scale involving multiple emergency departments across Canada. Completion of a larger study across multiple sites with more patients will improve our understanding of how fluid choice influences patient-important outcomes such as faster resolution of DKA (meaning patients can leave hospital sooner), fewer admissions to the intensive care unit, fewer deaths and fewer cases of permanent kidney damage. A total of 52 participants (26 per group) will be recruited for this pilot trial. This pilot study will assess the practicality of enrolling patients in London and help identify barriers and problems with running a larger trial. The overall goal is to determine if Ringer's Lactate will resolve DKA faster than normal saline. If this is true, patients may spend less time in the hospital, which benefits both individual patients and the healthcare system overall. If this hypothesis is correct, findings could provide high-level proof to change current practice guidelines and affect DKA management globally.

Conditions

Diabetic Ketoacidosis

Keywords

randomized controlled trial; emergency department; intravenous fluids; normal saline; Ringer's lactate/balanced crystalloid

Outcome Measures

Primary Outcomes (2)

• Patient Recruitment Rate (Feasibility Outcome)

  The primary feasibility outcome is patient recruitment rate over the one-year study period. We will also measure adherence to the protocol for this pilot study. This pilot is not powered to determine differences in treatment groups; however, a priori outcome definition and accurate outcome assessment is needed to inform the future study.

  One year

• Time to DKA Resolution (Efficacy Outcome)

  Time to DKA resolution (hours), defined as the time elapsed between ED presentation and ketoacidosis resolution, following criteria from the American Diabetes Association Consensus Statement on Hyperglycemic Crises1 (plasma glucose \<11.1 mmol/L and two of: plasma bicarbonate ≥15mmol/L, venous pH \>7.3 or anion gap ≤12mmol/L).

  Up to 48 hours

Secondary Outcomes (7)

• Time to Insulin Infusion Discontinuation

  Up to 48 hours

• Intensive Care Unit Admission

  30 days

• In-hospital Death

  30 days

• Hospital Length of Stay

  30 days

• Hyper- or Hypo-kalemia Post-emergency Department

  30 days

Study Arms (2)

Ringer's lactate

EXPERIMENTAL

The intervention is administration of IV Ringer's lactate. Rate of study fluid will be at the treating physician's (both ED and inpatient, if consulted for admission) discretion. Apart from fluid administered, there will be no other changes to the patient's clinical care, and patients will receive standard DKA treatment which may include insulin, electrolyte replacement, and/or supportive management. Pharmacy-prepared kits of 8 x 1L bags of study fluid (in Self et al., a maximum of 7090mL was given8) will be kept in a secure space within the ED. Once packaged, IV bags are useable for 30 days before expiration. If a kit is opened but not used completely, individual 1L bags may be returned to the pharmacy to save on costs.

Other: Ringer's lactate

Normal saline

ACTIVE COMPARATOR

The comparator is administration of IV normal saline. Rate of study fluid will be at the treating physician's (both ED and inpatient, if consulted for admission) discretion. Apart from fluid administered, there will be no other changes to the patient's clinical care, and patients will receive standard DKA treatment which may include insulin, electrolyte replacement, and/or supportive management. Pharmacy-prepared kits of 8 x 1L bags of study fluid (in Self et al., a maximum of 7090mL was given8) will be kept in a secure space within the ED. Once packaged, IV bags are useable for 30 days before expiration. If a kit is opened but not used completely, individual 1L bags may be returned to the pharmacy to save on costs.

Other: Ringer's lactate

Interventions

Ringer's lactate OTHER

Ringer's lactate is the most commonly used balanced crystalloid. Compared to normal saline, balanced crystalloids have chloride concentrations similar to human plasma; therefore, treatment with balanced crystalloids may lead to faster DKA resolution.

Also known as: Lactated ringers

Normal saline; Ringer's lactate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• There are no definitive criteria for diagnosing DKA.3 Thus, using the criteria employed by Self et al.8 and the Diabetes Canada guidelines3 we will include ED patients ≥18 years with a clinical diagnosis and laboratory values consistent with DKA, including:
• plasma glucose concentration ≥14mmol/L
• plasma bicarbonate concentration ≤18mmol/L and/or blood pH ≤7.30
• calculated anion gap \>10mmol/L
• presence of ketones/beta-hydroxybutyrate in serum and/or urine

You may not qualify if:

• We will exclude patients who:
• Are initially seen at another ED and transferred to LHSC for care and/or admission
• Receive \>1L of IV fluid prior to enrolment (e.g. pre-hospital by EMS or while waiting to be seen) - this may cause study contamination
• Are initially enrolled due to clinical suspicion of DKA based on elevated point-of-care glucose, but ultimately do not meet clinical/laboratory criteria for DKA (e.g. "hyperglycemia" only)
• Have euglycemic DKA (generally those on SGLT-2 inhibitors)

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

London Health Sciences Centre - Victoria Campus

London, Ontario, N6A5W9, Canada

Location

Related Publications (18)

• Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43. doi: 10.2337/dc09-9032. No abstract available.

  PMID: 19564476 BACKGROUND

• Roberts A, James J, Dhatariya K; Joint British Diabetes Societies (JBDS) for Inpatient Care. Management of hyperglycaemia and steroid (glucocorticoid) therapy: a guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care group. Diabet Med. 2018 Aug;35(8):1011-1017. doi: 10.1111/dme.13675.

  PMID: 30152586 BACKGROUND

• Diabetes Canada Clinical Practice Guidelines Expert Committee; Goguen J, Gilbert J. Hyperglycemic Emergencies in Adults. Can J Diabetes. 2018 Apr;42 Suppl 1:S109-S114. doi: 10.1016/j.jcjd.2017.10.013. No abstract available.

  PMID: 29650082 BACKGROUND

• Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med. 2013 Sep 26;369(13):1243-51. doi: 10.1056/NEJMra1208627. No abstract available.

  PMID: 24066745 BACKGROUND

• Casey JD, Brown RM, Semler MW. Resuscitation fluids. Curr Opin Crit Care. 2018 Dec;24(6):512-518. doi: 10.1097/MCC.0000000000000551.

  PMID: 30247219 BACKGROUND

• Morgan TJ, Venkatesh B, Hall J. Crystalloid strong ion difference determines metabolic acid-base change during acute normovolaemic haemodilution. Intensive Care Med. 2004 Jul;30(7):1432-7. doi: 10.1007/s00134-004-2176-x. Epub 2004 Feb 28.

  PMID: 14991093 BACKGROUND

• Omron EM, Omron RM. A physicochemical model of crystalloid infusion on acid-base status. J Intensive Care Med. 2010 Sep;25(5):271-80. doi: 10.1177/0885066610371633.

  PMID: 20622258 BACKGROUND

• Self WH, Evans CS, Jenkins CA, Brown RM, Casey JD, Collins SP, Coston TD, Felbinger M, Flemmons LN, Hellervik SM, Lindsell CJ, Liu D, McCoin NS, Niswender KD, Slovis CM, Stollings JL, Wang L, Rice TW, Semler MW; Pragmatic Critical Care Research Group. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA Netw Open. 2020 Nov 2;3(11):e2024596. doi: 10.1001/jamanetworkopen.2020.24596.

  PMID: 33196806 BACKGROUND

• Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):829-839. doi: 10.1056/NEJMoa1711584. Epub 2018 Feb 27.

  PMID: 29485925 BACKGROUND

• Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, Slovis CM, Lindsell CJ, Ehrenfeld JM, Siew ED, Shaw AD, Bernard GR, Rice TW; SALT-ED Investigators. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):819-828. doi: 10.1056/NEJMoa1711586. Epub 2018 Feb 27.

  PMID: 29485926 BACKGROUND

• Mahler SA, Conrad SA, Wang H, Arnold TC. Resuscitation with balanced electrolyte solution prevents hyperchloremic metabolic acidosis in patients with diabetic ketoacidosis. Am J Emerg Med. 2011 Jul;29(6):670-4. doi: 10.1016/j.ajem.2010.02.004. Epub 2010 May 1.

  PMID: 20825879 BACKGROUND

• Van Zyl DG, Rheeder P, Delport E. Fluid management in diabetic-acidosis--Ringer's lactate versus normal saline: a randomized controlled trial. QJM. 2012 Apr;105(4):337-43. doi: 10.1093/qjmed/hcr226. Epub 2011 Nov 22.

  PMID: 22109683 BACKGROUND

• Yung M, Letton G, Keeley S. Controlled trial of Hartmann's solution versus 0.9% saline for diabetic ketoacidosis. J Paediatr Child Health. 2017 Jan;53(1):12-17. doi: 10.1111/jpc.13436.

  PMID: 28070957 BACKGROUND

• Williams V, Jayashree M, Nallasamy K, Dayal D, Rawat A. 0.9% saline versus Plasma-Lyte as initial fluid in children with diabetic ketoacidosis (SPinK trial): a double-blind randomized controlled trial. Crit Care. 2020 Jan 2;24(1):1. doi: 10.1186/s13054-019-2683-3.

  PMID: 31898531 BACKGROUND

• Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA; PAFS consensus group. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016 Oct 24;355:i5239. doi: 10.1136/bmj.i5239.

  PMID: 27777223 BACKGROUND

• Wang X, Ji X. Sample Size Estimation in Clinical Research: From Randomized Controlled Trials to Observational Studies. Chest. 2020 Jul;158(1S):S12-S20. doi: 10.1016/j.chest.2020.03.010.

  PMID: 32658647 BACKGROUND

• Yan JW, Slim A, Van Aarsen K, Choi YH, Byrne C, Poonai N, Collins H, Clemens KK. Balanced crystalloids (RInger's lactate) versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department (BRISK-ED): a pilot randomised controlled trial. Emerg Med J. 2024 Jan 22;41(2):103-111. doi: 10.1136/emermed-2023-213290.

  PMID: 38050056 DERIVED

• Yan JW, Slim A, Van Aarsen K, Choi YH, Byrne C, Poonai N, Collins H, Clemens KK. Balanced crystalloids (RInger's lactate) versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department (BRISK-ED): a protocol for a pilot randomized controlled trial. Pilot Feasibility Stud. 2023 Jul 13;9(1):121. doi: 10.1186/s40814-023-01356-5.

  PMID: 37443083 DERIVED

MeSH Terms

Conditions

Diabetic Ketoacidosis; Emergencies

Interventions

Ringer's Lactate

Condition Hierarchy (Ancestors)

Ketosis; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Kristine Van Aarsen (Research Associate)
• Organization: Lawson Health Research Institute

kristine.vanaarsen@lhsc.on.ca

5196858500

Study Officials

• Justin W Yan, MD, MSc

  Lawson Health Research Institute/Western University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The patients, treating physicians, and outcome assessors will be blinded to assigned treatment. Our pharmacy will prepare an opaque covering over each fluid bag within study kits, which will not be removed during the infusion to maintain blinding. Each bag will be labelled with a kit number and scannable bar code to ensure the patient receives study fluid as ordered which will be entered on their Medication Administration Record.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a single-centre, triple-blind pilot RCT evaluating the superiority of IV RL (intervention) compared to saline (comparator) in treating adult ED patients presenting with DKA over a one-year period.

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 15, 2021
• Study Start: October 12, 2021
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022
• Last Updated: January 13, 2025
• Results First Posted: January 13, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)