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Randomized Control Trial of Fluid Therapy for Pediatric Diabetic Ketoacidosis

This study has been completed.
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT01365793
First received: June 1, 2011
Last updated: May 12, 2017
Last verified: May 2017
  Purpose

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.


Condition Intervention Phase
Cerebral Edema
Diabetic Ketoacidosis
Drug: 0.45% saline replacement fluid
Drug: 0.9% saline replacement fluid
Drug: 0.45% saline intravenous fluid
Drug: 0.9% saline Intravenous fluid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Fluid Therapy and Cerebral Injury in Pediatric Diabetic Ketoacidosis

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Glasgow Coma Score < 14 within the first 24 hours of treatment for DKA. [ Time Frame: 24 hours ]
    The primary outcome is the binary indicator that a patient's GCS score drops below 14 (i.e. abnormal score) within the first 24 hours of treatment of DKA. There will be two treatment factors: sodium concentration of re-hydration fluids and rate of rehydration. These effects will be tested separately, using the Mantel-Haenszel chi-square test, stratified by hospital, and by the other main factor.


Secondary Outcome Measures:
  • Frequency of clinically apparent cerebral edema during DKA treatment [ Time Frame: 24 hours ]
    GCS scores between the 4 groups will be compared using a Wilcoxon rank- sum test or a Van Elteren test, stratified by hospital. Patients presenting with GCS scores < 14 will be included in this analysis. The outcome will be difference between GCS score at presentation and lowest recorded GCS score, with death as the worst possible ranking.

  • Median scores on digit span testing during DKA treatment [ Time Frame: 24 hours ]
    Digit span scores are measured as the longest span correctly recited in each of the assessment sessions. Separate analyses will be conducted for the forward and backward spans. Digit span scores can be analyzed using para- metric methods. The trajectory of digit span scores during the course of the hospitalization can be used to assess patients rates of recovery and whether this rate varies systematically as a function of treatment protocol.

  • Mean scores on tests of memory capacity 3 months after recovery from DKA. [ Time Frame: 3 months ]
    The effects of treatment conditions on memory function will be examined in separate analyses of variance (ANOVA) in which each of the indices of the memory performance will be considered as outcomes. The proposed memory tasks yield two indices of performance, recollection of item-context associations and item recognition. Memory function after recovery from DKA will also be compared with memory function of children with type 1 diabetes without DKA.

  • Mean scores on IQ tests 3 months after recovery from DKA [ Time Frame: 3 months ]
    The same analytical approach proposed for memory will be used for the analyses of IQ measures. Each test will provide three scores: a verbal IQ, and performance IQ, and a total IQ score. Each of these three IQ measures will be analyzed using ANOVA. Mean IQ scores will also be compared with IQ scores of children with type 1 diabetes without DKA.


Enrollment: 1405
Study Start Date: November 2010
Study Completion Date: January 2017
Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rapid rehydration using 0.45% saline replacement fluid
This arm will involve more rapid intravenous fluid treatment which will include a second 10cc/Kg bolus of 0.9% saline and assume a 10% fluid deficit. 0.45% saline will be used as the replacement fluid for this arm.
Drug: 0.45% saline replacement fluid
10cc/Kg bolus of 0.9% saline followed by 0.45% saline used as the replacement fluid
Experimental: Rapid rehydration using 0.9% saline replacement fluid
This arm will involve more rapid intravenous fluid treatment which will include a second 10cc/Kg bolus of 0.9% saline and assume a 10% fluid deficit. 0.9% saline will be used as the replacement fluid.
Drug: 0.9% saline replacement fluid
10cc/Kg bolus of 0.9% saline followed by 0.9% saline used as the replacement fluid.
Experimental: Slower rehydration using 0.45% saline intravenous fluid
This arm will involve slower rehydration (assumed 5% fluid deficit and no additional fluid bolus) with 0.45% saline used as the replacement fluid.
Drug: 0.45% saline intravenous fluid
0.45% saline fluid
Experimental: Slower rehydration using 0.9% saline intravenous fluid
This arm will involve slower rehydration (assumed 5% fluid deficit and no additional fuid bolus) with 0.9% saline used as the replacement fluid.
Drug: 0.9% saline Intravenous fluid
0.9% saline fluid

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

Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01365793

Locations
United States, California
University of California, Davis
Sacramento, California, United States, 95817
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, D.C., District of Columbia, United States, 20010
United States, Illinois
Ann & Robert Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60614
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University & St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Hasbro Children's Hospital/Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84158
Sponsors and Collaborators
University of California, Davis
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Nathan Kuppermann, MD, MPH University of California, Davis
Principal Investigator: Nicole S Glaser, MD University of California, Davis
  More Information

Additional Information:
Publications:
Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT01365793     History of Changes
Other Study ID Numbers: 200917444
U01HD062417 ( US NIH Grant/Contract Award Number )
Study First Received: June 1, 2011
Last Updated: May 12, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by University of California, Davis:
cerebral edema
diabetic ketoacidosis
pediatric diabetes
fluid therapy

Additional relevant MeSH terms:
Ketosis
Acidosis
Diabetic Ketoacidosis
Brain Edema
Acid-Base Imbalance
Metabolic Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Diabetes Complications
Endocrine System Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on May 22, 2017