Trial Outcomes & Findings for Intravenous Fluids in Adults With Diabetic Ketoacidosis in the Emergency Department (NCT NCT04926740)

NCT ID: NCT04926740

Last Updated: 2025-01-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 74 participants
• Primary outcome timeframe: One year
• Results posted on: 2025-01-13

Participant Flow

We approached 74 patients for consent during the study period at our site and 8 declined participation.

Participant milestones

Measure	Ringer's Lactate 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. Ringer's lactate: 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.	Normal Saline 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. Ringer's lactate: 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.
Overall Study STARTED	34	32
Overall Study COMPLETED	25	27
Overall Study NOT COMPLETED	9	5

Reasons for withdrawal

Measure	Ringer's Lactate 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. Ringer's lactate: 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.	Normal Saline 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. Ringer's lactate: 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.
Overall Study Ineligible: received >1L of pre-study fluid prior to enrolment	2	1
Overall Study Ineligible: subsequently found to not have true DKA	7	4

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Ringer's Lactate n=25 Participants 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. Ringer's lactate: 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.	Normal Saline n=27 Participants 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. Ringer's lactate: 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.	Total n=52 Participants Total of all reporting groups
Age, Continuous	47 years n=25 Participants	43 years n=27 Participants	46 years n=52 Participants
Sex: Female, Male Female	9 Participants n=25 Participants	12 Participants n=27 Participants	21 Participants n=52 Participants
Sex: Female, Male Male	16 Participants n=25 Participants	15 Participants n=27 Participants	31 Participants n=52 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Diabetes type Type 1	9 Participants n=25 Participants	17 Participants n=27 Participants	26 Participants n=52 Participants
Diabetes type Type 2	14 Participants n=25 Participants	8 Participants n=27 Participants	22 Participants n=52 Participants
Diabetes type New diagnosis	2 Participants n=25 Participants	2 Participants n=27 Participants	4 Participants n=52 Participants
Comorbidities Psychiatric illness	10 participants n=25 Participants	11 participants n=27 Participants	21 participants n=52 Participants
Comorbidities Hypertension	9 participants n=25 Participants	12 participants n=27 Participants	21 participants n=52 Participants
Comorbidities Dyslipidemia	6 participants n=25 Participants	6 participants n=27 Participants	12 participants n=52 Participants

PRIMARY outcome

Timeframe: One year

Population: We approached 74 patients for consent and 8 declined participation. Ultimately, we randomized 66 patients to receive RL (34 patients) or NS (32 patients); thus, our recruitment rate was 66/74 (89.2%).

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.

Outcome measures

Measure	Patient Recruitment Rate n=74 Participants Feasibility outcome	Ringer's Lactate 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. Ringer's lactate: 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.
Patient Recruitment Rate (Feasibility Outcome)	66 Participants	—

PRIMARY outcome

Timeframe: Up to 48 hours

Population: Of 66 overall patients consented, 14 were subsequently excluded upon further review as they did not meet criteria for DKA or received greater than 1 litre of fluid before randomization, leaving 52 included patients in our study. Due to a pharmacy error with respect to the allocation list for one patient, there were 25 patients in the RL group and 27 in the NS group.

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).

Outcome measures

Measure	Patient Recruitment Rate n=27 Participants Feasibility outcome	Ringer's Lactate n=25 Participants 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. Ringer's lactate: 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.
Time to DKA Resolution (Efficacy Outcome)	12.7 hours Interval 7.9 to 19.2	15.7 hours Interval 10.4 to 18.8

SECONDARY outcome

Timeframe: Up to 48 hours

Time to insulin infusion discontinuation

Outcome measures

Measure	Patient Recruitment Rate n=25 Participants Feasibility outcome	Ringer's Lactate n=27 Participants 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. Ringer's lactate: 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.
Time to Insulin Infusion Discontinuation	15.9 hours Interval 5.7 to 39.2	15.5 hours Interval 6.7 to 36.4

SECONDARY outcome

Timeframe: 30 days

Intensive care unit admission

Outcome measures

Measure	Patient Recruitment Rate n=25 Participants Feasibility outcome	Ringer's Lactate n=27 Participants 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. Ringer's lactate: 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.
Intensive Care Unit Admission	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 30 days

In-hospital death

Outcome measures

Measure	Patient Recruitment Rate n=25 Participants Feasibility outcome	Ringer's Lactate n=27 Participants 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. Ringer's lactate: 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.
In-hospital Death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 30 days

Hospital length of stay

Outcome measures

Measure	Patient Recruitment Rate n=25 Participants Feasibility outcome	Ringer's Lactate n=27 Participants 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. Ringer's lactate: 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.
Hospital Length of Stay	3.3 hours Interval 2.0 to 6.1	1.4 hours Interval 0.3 to 5.8

SECONDARY outcome

Timeframe: 30 days

>6.0 or <3.0 mmol/L

Outcome measures

Measure	Patient Recruitment Rate n=25 Participants Feasibility outcome	Ringer's Lactate n=27 Participants 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. Ringer's lactate: 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.
Hyper- or Hypo-kalemia Post-emergency Department	24 Participants	12 Participants

SECONDARY outcome

Timeframe: 30 days

Serum creatinine increase >200% from baseline or <0.5mL/kg/hr urine output for <12 hours

Outcome measures

Measure	Patient Recruitment Rate n=25 Participants Feasibility outcome	Ringer's Lactate n=27 Participants 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. Ringer's lactate: 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.
In-hospital Acute Kidney Injury (Stage 2 or Greater) Post-emergency Department	4 Participants	3 Participants

SECONDARY outcome

Timeframe: 30 days

Composite of i) death, ii) new renal replacement therapy, iii) final serum creatinine >/= 200% baseline at the earliest of hospital discharge or 30 days after ED presentation

Outcome measures

Measure	Patient Recruitment Rate n=25 Participants Feasibility outcome	Ringer's Lactate n=27 Participants 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. Ringer's lactate: 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.
Major Adverse Kidney Events	4 events	2 events

Adverse Events

Ringer's Lactate

Serious events: 7 serious events

Other events: 0 other events

Deaths: 0 deaths

Normal Saline

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ringer's Lactate n=25 participants at risk 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. Ringer's lactate: 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.	Normal Saline n=27 participants at risk 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. Ringer's lactate: 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.
Renal and urinary disorders Major adverse kidney event within 30 days of ED presentation	16.0% 4/25 • Number of events 4 • 30 days Adverse event = death, intensive care unit admission, intubation, in-hospital acute kidney injury, and major adverse kidney events at 30 days	7.4% 2/27 • Number of events 2 • 30 days Adverse event = death, intensive care unit admission, intubation, in-hospital acute kidney injury, and major adverse kidney events at 30 days
General disorders Intensive Care Unit Admission	4.0% 1/25 • Number of events 1 • 30 days Adverse event = death, intensive care unit admission, intubation, in-hospital acute kidney injury, and major adverse kidney events at 30 days	3.7% 1/27 • Number of events 1 • 30 days Adverse event = death, intensive care unit admission, intubation, in-hospital acute kidney injury, and major adverse kidney events at 30 days
Surgical and medical procedures Intubation	8.0% 2/25 • Number of events 2 • 30 days Adverse event = death, intensive care unit admission, intubation, in-hospital acute kidney injury, and major adverse kidney events at 30 days	0.00% 0/27 • 30 days Adverse event = death, intensive care unit admission, intubation, in-hospital acute kidney injury, and major adverse kidney events at 30 days
Renal and urinary disorders Acute kidney injury (in-hospital)	0.00% 0/25 • 30 days Adverse event = death, intensive care unit admission, intubation, in-hospital acute kidney injury, and major adverse kidney events at 30 days	3.7% 1/27 • Number of events 1 • 30 days Adverse event = death, intensive care unit admission, intubation, in-hospital acute kidney injury, and major adverse kidney events at 30 days

Other adverse events

Adverse event data not reported

Additional Information

Kristine Van Aarsen (Research Associate)

Lawson Health Research Institute

Phone: 5196858500

Email: kristine.vanaarsen@lhsc.on.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place