Randomized Control Trial of Fluid Therapy for Pediatric Diabetic Ketoacidosis
|ClinicalTrials.gov Identifier: NCT01365793|
Recruitment Status : Completed
First Posted : June 3, 2011
Last Update Posted : October 31, 2017
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 or disease||Intervention/treatment||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 (Clinical Trial)|
|Actual Enrollment :||1405 participants|
|Intervention Model:||Factorial Assignment|
|Masking:||None (Open Label)|
|Official Title:||Fluid Therapy and Cerebral Injury in Pediatric Diabetic Ketoacidosis|
|Study Start Date :||November 2010|
|Actual Primary Completion Date :||September 2016|
|Actual Study Completion Date :||January 2017|
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
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01365793
|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|
|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|
|Principal Investigator:||Nathan Kuppermann, MD, MPH||University of California, Davis|
|Principal Investigator:||Nicole S Glaser, MD||University of California, Davis|