Randomized Control Trial of Fluid Therapy for Pediatric Diabetic Ketoacidosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of California, Davis
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT01365793
First received: June 1, 2011
Last updated: August 6, 2014
Last verified: August 2014
  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
Other: Intravenous fluid
Other: intravenous fluid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 1510
Study Start Date: November 2010
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rapid rehydration using 0.45% saline
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.
Other: Intravenous 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
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.
Other: intravenous 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
This arm will involve slower rehydration (assumed 5% fluid deficit and no additional fluid bolus) with 0.45% saline used as the replacement fluid.
Other: intravenous fluid
0.45% saline fluid
Experimental: Slower rehydration using 0.9% saline
This arm will involve slower rehydration (assumed 5% fluid deficit and no additional fuid bolus) with 0.9% saline used as the replacement fluid.
Other: 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
Genders Eligible for Study:   Both
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

Contacts
Contact: Nathan Kuppermann, MD, MPH 916-734-1535 nkuppermann@ucdavis.edu
Contact: Nicole S Glaser, MD 916-734-0406 nsglaser@ucdavis.edu

Locations
United States, California
University of California, Davis Recruiting
Sacramento, California, United States, 95817
Contact: Nathan Kuppermann, MD, MPH    916-734-1535    nkuppermann@ucdavis.edu   
Contact: Nicole S Glaser, MD    916-734-0406    nsglaser@ucdavis.edu   
Principal Investigator: Nathan Kuppermann, MD, MPH         
Principal Investigator: Nicole S Glaser, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Arleta Rewers, MD    303-724-2576    arleta.rewers@childrenscolorado.org   
Contact: Lalit Bajaj, MD       lalit.bajaj@childrenscolorado.org   
Principal Investigator: Arleta Rewers, MD         
United States, Delaware
Alfred I. duPont Hospital for Children Recruiting
Wilmington, Delaware, United States, 19803
Contact: Andrew DePiero, MD    302-651-5889    adepiero@NEMOURS.ORG   
Principal Investigator: Andrew DePiero, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, D.C., District of Columbia, United States, 20010
Contact: Kathleen Brown, MD    202-476-4177    kbrown@childrensnational.org   
Contact: James Chamberlain, MD       jchamber@childrensnational.org   
Principal Investigator: Kathleen Brown, MD         
United States, Illinois
Ann & Robert Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60614
Contact: Jennifer Trainor, MD    773-880-8245    jtrainor@luriechildrens.org   
Contact: Elizabeth Powell, MD    773-880-4000    epowell@luriechildrens.org   
Principal Investigator: Jennifer Trainor, MD         
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lise E Nigrovic, MD, MPH    617-355-6000    lise.nigrovic@childrens.harvard.edu   
Principal Investigator: Lise E Nigrovic, MD, MPH         
United States, Missouri
Washington University & St. Louis Children's Hospital Recruiting
St. Louis, Missouri, United States, 63110
Contact: Kimberly Quayle, MD    314-454-2341    quayle@kids.wustl.edu   
Contact: David Jaffe, MD    314-454-2341    jaffe@kids.wustl.edu   
Principal Investigator: Kimberly Quayle, MD         
United States, New York
Columbia University Recruiting
New York City, New York, United States, 10032
Contact: Maria Kwok, MD    212-305-8319    myk2102@columbia.edu   
Contact: Peter S Dayan, MD    212-342-4176    psd9@columbia.edu   
Principal Investigator: Maria Kwok, MD         
Sub-Investigator: John S Baird, MD         
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Michael J Stoner, MD    614-722-4385    michael.stoner@nationwidechildrens.org   
Principal Investigator: Michael J Stoner, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Sage Myers, MD    215-590-1944    myerss@email.chop.edu   
Contact: Joseph Zorc, MD    215-590-1944    zorc@email.chop.edu   
Principal Investigator: Sage Myers, MD         
United States, Rhode Island
Hasbro Children's Hospital/Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Aris Garro, MD, MPH    401-444-4900    arisgarro1@gmail.com   
Principal Investigator: Aris Garro, MD         
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Julie McManemy, MD    832-824-5497    cgmacias@texaschildrens.org   
Contact: Charles G Macias, MD, MPH    832.824.5416    cgmacias@texaschildrens.org   
Principal Investigator: Julie McManemy, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84158
Contact: Jeff Schunk, MD    801-587-7427    jeff.schunk@hsc.utah.edu   
Contact: Douglas Nelson, MD    801-587-7450    doug.nelson@hsc.utah.edu   
Principal Investigator: Jeff Schunk, MD         
Sponsors and Collaborators
University of California, Davis
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: 200917444-1, U01HD062417
Study First Received: June 1, 2011
Last Updated: August 6, 2014
Health Authority: United States: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on October 29, 2014