Clinical trial NCT01365793: Randomized Control Trial of Fluid Therapy for Pediatric Diabetic Ketoacidosis
Official title: Fluid Therapy and Cerebral Injury in Pediatric Diabetic Ketoacidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cerebral Edema
Diabetic Ketoacidosis
Keywords: cerebral edema
diabetic ketoacidosis
pediatric diabetes
fluid therapy
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2011-06-03
Enrollment: 1389
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The investigators will conduct a randomized controlled trial comparing four different intravenous (IV) fluid treatment protocols for pediatric diabetic ketoacidosis (DKA). Two rates of rehydration will be compared; a more rapid rate and a slower rate. Within each of these two basic rehydration protocols, the investigators will vary the type of rehydration fluid used (0.9% saline or 0.45% saline). The investigators will compare the different treatments by conducting assessments of neurological injury, by measuring the frequency of significant cerebral edema, and by measuring long-term neurocognitive function.

These studies will allow us to determine whether variations in IV fluid treatment protocols affect acute neurological outcomes of DKA. Additionally, they will provide important data regarding the impact of DKA and DKA treatment on long-term neurocognitive function in children. In this way, the investigators hope to identify a more ideal fluid management strategy for children with DKA.

Previous studies have suggested that DKA may cause blood flow to the brain to be reduced and that brain injury might result from this reduction in blood flow and/or the effects of re-establishment of normal blood flow during DKA treatment with insulin and iv fluids. The investigators hypothesize that more rapidly re-establishing normal blood flow to the brain during DKA, by giving fluids more rapidly and using fluids with a higher sodium (salt) content, will help to minimize brain injury caused by DKA.

Detailed description: These data will be compared to observational data from children with type 1 diabetes without DKA.

Eligibility criteria: Inclusion Criteria:

* must present or be transferred to a participating emergency department
* age less than 18 years
* diagnosis of DKA

  * serum glucose or fingerstick glucose concentration \>300 mg/dL
  * venous pH \< 7.25 OR serum bicarbonate concentration \< 15 mmol/L.

Exclusion Criteria:

* patients with underlying neurological disorders or neurocognitive deficits which would affect either mental status testing during treatment or subsequent neurocognitive testing after recovery
* patients who present with concomitant alcohol or drug use, head trauma, meningitis or other conditions which might affect neurological function
* patients transferred to one of the participating emergency departments after initiation of DKA treatment other than one 10cc/kg intravenous bolus of 0.9% saline
* patients who are known to be pregnant at time of ED evaluation
* patients who have been enrolled in this study twice previously
* patients for whom the treating physician believed a specific fluid and electrolyte regimen was warranted
* patients for whom informed consent could not be obtained within 1 hour after completion of the initial fluid bolus, or within 2 hours from initiation of fluids, whichever is longer
* Patients who have been receiving IV fluids at a maintenance rate or greater (defined by the 4-2-1 rule) for more than two hours; OR
* Patients for whom it has been more than four hours since DKA therapy (IV fluids, IV bolus, or IV insulin) began; OR
* Patients who have been given hyperosmolar therapy (i.e. mannitol or 3% normal saline) prior to or since arriving at one of the participating PECARN emergency departments; OR
* Patients for whom the treating physician intends to immediately administer hyperosmolar therapy (i.e. mannitol or 3% normal saline); OR
* Patients whose baseline GCS is 11 or less.

Primary outcomes:
measure: the Number of Participants With Glasgow Coma Score (GCS) < 14 Within the First 24 Hours of Treatment for Diabetic Ketoacidosis (DKA)
timeFrame: 24 hours
Secondary outcomes:
measure: Frequency of Clinically Apparent Brain Injury
timeFrame: 24 hours
measure: Hourly Improvement in Forward and Backward Digit Span Scores During DKA Treatment (Mean Difference Per Hour)
timeFrame: 24 hours
measure: Mean Scores on Tests of Memory Capacity 3 Months After Recovery From DKA.
timeFrame: 3 months
measure: Intelligence Quotient (IQ) Testing
timeFrame: 3 months
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Alfred I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Ann & Robert Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University & St. Louis Children's Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Providence
country: United States
facility: Hasbro Children's Hospital/Rhode Island Hospital
state: Rhode Island
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of California, Davis
name: Nathan Kuppermann, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: Nicole S Glaser, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Glaser NS, Ghetti S, Casper TC, Dean JM, Kuppermann N; Pediatric Emergency Care Applied Research Network (PECARN) DKA FLUID Study Group. Pediatric diabetic ketoacidosis, fluid therapy, and cerebral injury: the design of a factorial randomized controlled trial. Pediatr Diabetes. 2013 Sep;14(6):435-46. doi: 10.1111/pedi.12027. Epub 2013 Mar 13.