Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03066440 |
| Other study ID # |
00001394 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2018 |
| Est. completion date |
March 18, 2024 |
Study information
| Verified date |
March 2024 |
| Source |
State University of New York at Buffalo |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Objectives: Intravenous (IV) fluid administration is a fundamental component of diabetic
ketoacidosis (DKA) treatment. Normal saline (NS), the most common IV fluid used in DKA
management, contains more chloride than human blood. Excessive amounts of chloride have been
shown to cause a detrimental metabolic acidosis. Other IV fluids have more physiologic
chloride levels, such as lactated ringers (LR). This study will compare the rates of
hyperchloremic metabolic acidosis in children treated with NS to those treated with LR to
determine the effect on overall length of acidosis and length of stay in the hospital or
intensive care unit.
Design: Single-center, double blinded, randomized controlled trial.
Subjects: Children aged 0 to 18 years who present with diabetic ketoacidosis and require
pediatric intensive care unit admission. Patients with evidence of shock, multi-organ failure
or clinically significant cerebral edema will be excluded. The projected study population
will be 104 patients, 52 in each arm.
Interventions: Patients will be enrolled within 1 hour of presentation to the emergency room
or pediatric intensive care unit if transferred directly from another facility. They will be
randomized to receive intravenous fluids containing 0.9% saline or lactated ringers. All
patients will be treated using the institutional DKA protocol with the content of the
intravenous fluids being the only difference in treatment between arms. Study intervention
lasts until the end of the acute management of DKA.
Planned measurements and study outcomes: The primary study outcome will be duration of
metabolic acidosis. Resolution of metabolic acidosis will be defined in three ways: 1.
Normalization of the ketosis; 2. Normalization of the serum pH; 3. Normalization of the serum
bicarbonate level. Secondary outcomes will include length of stay in the pediatric intensive
care unit and length of stay in the hospital. All outcomes will be correlated with the
overall chloride load given via intravenous fluids during DKA management. Regression
modelling will control for any baseline differences between the groups in regards to severity
of DKA, and if newly diagnosed or poorly controlled diabetes mellitus.
Description:
There have been limited prospective clinical studies in pediatrics patients examining the
association of the chloride content of intravenous fluids and outcome in DKA. This
prospective randomized controlled trial is being performed to compare the duration of
acidosis and hospital length of stay in children with DKA who are admitted to a pediatric
intensive care unit and are treated with intravenous fluids containing NS or LR. The primary
study hypothesis is that use of LR will be associated with decreased duration of
hyperchloremic metabolic acidosis and, therefore, shorter hospitalization than use of NS in
the treatment of pediatric DKA.
Primary hypothesis: Children with diabetic ketoacidosis (DKA) who are treated with
intravenous fluids containing lactated ringers (LR) will have a shorter duration of
hyperchloremic metabolic acidosis after hospital admission than those treated with
intravenous fluids containing normal saline (NS).
Secondary hypothesis: The duration of acidosis after hospital admission in children with DKA
will be associated with length of stay in the intensive care unit and hospital.
Outcomes
Primary outcome
The primary study outcome will be duration of metabolic acidosis. Resolution of metabolic
acidosis will be defined in three ways:
1. Serum ketone level <1mmol/L;
2. Venous pH > 7.3;
3. Serum bicarbonate level > 18mmol/L.
Secondary outcomes Secondary outcomes will include length of stay in the pediatric intensive
care unit (PICU) and length of stay in the hospital.
Study design This is a single center, double blinded, randomized controlled trial with two
treatment arms performed at a tertiary care children's hospital. Patients will be randomized
within an hour of presentation to the hospital to receive DKA management using intravenous
fluids containing primarily normal saline or lactated ringers. All other aspects of DKA
management will be the same in each arm, per the institution protocol. Since both treatment
arms involve using intravenous fluids which are considered standard of care in treating
dehydration, a waiver of consent will be requested.
Recruitment methods Patients will be eligible for enrollment and randomization if they are
admitted to the pediatric emergency room or pediatric intensive care unit from an outside
hospital or facility with DKA and they meet inclusion criteria. Patients will be screened by
emergency room personnel for eligibility and if PICU admission is determined, patients will
be enrolled. If transferred directly to the pediatric intensive care unit, pediatric critical
care fellow and attending physicians will be responsible for screening and enrollment 24
hours a day. Enrollment and randomization will occur within 1 hour of hospital presentation.
Enrollment will consist of assigning a randomization number at point of entry to the hospital
(Emergency Room or Pediatric Intensive Care Unit) and placing the study DKA order set.
Randomization methods Upon enrollment, patients will be assigned a randomization number in
sequential order from a previously generated randomization table provided by a statistician
and available in the ER and PICU to study personnel. Each number will correlate with a
treatment arm visible on a randomization table with coordinated treatment arm assignment
available only to pharmacy personnel. Pharmacy personnel will then provide the appropriate
content to the intravenous fluids with a generic label "DKA study fluids with dextrose" and
"DKA study fluids without dextrose." As the fluids look identical, they would only differ
visually in labelling, so standardized labelling as described here will allow all treating
physicians to be blinded to treatment arm assignment.
Study Intervention All enrolled patients will be treated using the institutional DKA
management protocol which is in place in the emergency room and the pediatric intensive care
unit and was developed in collaboration with the endocrinology division. The only difference
in the study protocol from the institutional DKA protocol is the intravenous fluid content.
Please refer to study protocol schematic shown in supplement 1.
Upon admission to the ER or PICU, all eligible patients will be placed on cardiac monitors,
admission DKA laboratory tests will be ordered and an initial intravenous fluid bolus of 10
ml/kg normal saline will be administered as is standard of care. These aspects of DKA
management will likely be performed before study enrollment, but if not, will be identical
for both arms so treatment arm assignment will not be affected. Subjects will be started on a
continuous insulin infusion drip at 0.1 U/kg/hr and study intravenous fluids without dextrose
at 1.5 times maintenance. Per standard of care, point of care whole blood glucose levels will
be followed hourly, serum blood gases and electrolytes every 2 hours, beta-hydroxybutyrate
levels every 6 hours and urine ketones every void. ER subjects will be transferred to the
PICU to continue exactly the same management and laboratory schedule.
The study protocol will be used until acute management for DKA using the continuous insulin
infusion is stopped. Our current practice is to convert from continuous insulin to
intermittent subcutaneous insulin administration when the venous pH is equal to or greater
than 7.30 and the serum bicarbonate level is equal to or greater than 15 mmol/L.
Fluid Management DKA fluid management is based on a two-bag system to maintain glucose levels
between 100 and 300 mg/dL as the ketosis is corrected. The first type of intravenous fluid
used has no dextrose in it to avoid worsening the initial hyperglycemia. Once the serum
glucose falls below 300 mg/dL, 10% dextrose-containing fluids will be started. All
intravenous fluids will contain 20millieqilivants per liter (mEq/L) of potassium acetate and
20mEq/L potassium phosphate.
Study fluid management will follow the same guidelines for rate of fluid delivery and amount
of dextrose used in the standard management of patients in DKA. Bedside healthcare personnel
will treat all study subjects identically regardless of treatment arm. To provide blinding to
all bedside staff, intravenous fluid bags will be labelled as "DKA study fluid with dextrose"
or "DKA study fluid without dextrose." All intravenous fluids used will have an electrolyte
composition of 20mEq/L of potassium acetate and 20mEq/L of potassium phosphate.
