Randomized Control Trial of Fluid Therapy for Pediatric Diabetic Ketoacidosis

NCT ID: NCT01365793

Last Updated: 2018-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1389 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2017-01-31

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.

Conditions

Cerebral Edema; Diabetic Ketoacidosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

0.45% saline replacement fluid

Intervention Type: DRUG

10cc/Kg bolus of 0.9% saline followed by 0.45% saline used as the replacement fluid

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.

Group Type: EXPERIMENTAL

0.9% saline replacement fluid

Intervention Type: DRUG

10cc/Kg bolus of 0.9% saline followed by 0.9% saline used as the replacement fluid.

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.

Group Type: EXPERIMENTAL

0.45% saline intravenous fluid

Intervention Type: DRUG

0.45% saline fluid

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.

Group Type: EXPERIMENTAL

0.9% saline Intravenous fluid

Intervention Type: DRUG

0.9% saline fluid

Interventions

0.45% saline replacement fluid

10cc/Kg bolus of 0.9% saline followed by 0.45% saline used as the replacement fluid

Intervention Type: DRUG

0.9% saline replacement fluid

10cc/Kg bolus of 0.9% saline followed by 0.9% saline used as the replacement fluid.

Intervention Type: DRUG

0.45% saline intravenous fluid

0.45% saline fluid

Intervention Type: DRUG

0.9% saline Intravenous fluid

0.9% saline fluid

Intervention Type: DRUG

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.

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nathan Kuppermann, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Nicole S Glaser, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

University of California, Davis

Sacramento, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Children's Hospital Boston

Boston, Massachusetts, United States

Washington University & St. Louis Children's Hospital

St Louis, Missouri, United States

Columbia University

New York, New York, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Hasbro Children's Hospital/Rhode Island Hospital

Providence, Rhode Island, United States

Texas Children's Hospital

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23490311 (View on PubMed)

Related Links

http://www.pecarn.org

Official website of the Pediatric Emergency Care Applied Research Network (PECARN), funded by HRSA/MCHB

Other Identifiers

U01HD062417

Identifier Type: NIH

Identifier Source: secondary_id

View Link

230233

Identifier Type: -

Identifier Source: org_study_id