Cerebral EdemaPhase 3NCT01365793
Randomized Control Trial of Fluid Therapy for Pediatric Diabetic Ketoacidosis
A Phase 3 study testing 0.45% saline replacement fluid, 0.9% saline replacement fluid and 0.45% saline intravenous fluid in people with Cerebral Edema and Diabetic Ketoacidosis, run by University of California, Davis at 13 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Cerebral Edema, Diabetic Ketoacidosis
- What is being tested?
- 0.45% saline replacement fluid, 0.9% saline replacement fluid and 0.45% saline intravenous fluid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,389 participants
- Where
- 13 sitesUnited States
- Study dates
- Nov 2010to Jan 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Children's Hospital Boston
Boston, Massachusetts, 02115
Ann & Robert Lurie Children's Hospital of Chicago
Chicago, Illinois, 60614
Nationwide Children's Hospital
Columbus, Ohio, 43205
Texas Children's Hospital
Houston, Texas, 77030
Columbia University
New York, New York, 10032
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Hasbro Children's Hospital/Rhode Island Hospital
Providence, Rhode Island, 02903
University of California, Davis
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84158
Washington University & St. Louis Children's Hospital
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803
About this study
Official title: Fluid Therapy and Cerebral Injury in Pediatric Diabetic Ketoacidosis
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.
Read the detailed description
These data will be compared to observational data from children with type 1 diabetes without DKA.
- Conditions
- Cerebral Edema, Diabetic Ketoacidosis
- Being tested
- 0.45% saline replacement fluid, 0.9% saline replacement fluid, 0.45% saline intravenous fluid, 0.9% saline Intravenous fluid
- Keywords
- cerebral edema, diabetic ketoacidosis, pediatric diabetes, fluid therapy
- Medical subject headings
- Brain Edema, Diabetic Ketoacidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
0.45% saline replacement fluidDrug
10cc/Kg bolus of 0.9% saline followed by 0.45% saline used as the replacement fluid
0.9% saline replacement fluidDrug
10cc/Kg bolus of 0.9% saline followed by 0.9% saline used as the replacement fluid.
0.45% saline intravenous fluidDrug
0.45% saline fluid
0.9% saline Intravenous fluidDrug
0.9% saline fluid
| Study group | Role | What they receive |
|---|---|---|
| Rapid rehydration using 0.45% saline replacement fluid | Experimental | 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. Receives: Drug: 0.45% saline replacement fluid |
| Rapid rehydration using 0.9% saline replacement fluid | Experimental | 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. Receives: Drug: 0.9% saline replacement fluid |
| Slower rehydration using 0.45% saline intravenous fluid | Experimental | This arm will involve slower rehydration (assumed 5% fluid deficit and no additional fluid bolus) with 0.45% saline used as the replacement fluid. Receives: Drug: 0.45% saline intravenous fluid |
| Slower rehydration using 0.9% saline intravenous fluid | Experimental | This arm will involve slower rehydration (assumed 5% fluid deficit and no additional fuid bolus) with 0.9% saline used as the replacement fluid. Receives: Drug: 0.9% saline Intravenous fluid |
What is being measured
The primary outcome is the main question the study is designed to answer.
the Number of Participants With Glasgow Coma Score (GCS) < 14 Within the First 24 Hours of Treatment for Diabetic Ketoacidosis (DKA)
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.
Measured: 24 hours
Secondary outcomes (4)
Frequency of Clinically Apparent Brain Injury
Deterioration in neurological status requiring interventions such as hyperosmolar therapy or endotracheal intubation, or resulting in death. This outcome was determined by an adjudication committee.
Measured: 24 hours
Hourly Improvement in Forward and Backward Digit Span Scores During DKA Treatment (Mean Difference Per Hour)
The Digit Span subtest is adapted from the Wechsler Intelligence Scale for Children, 4th version (WISC-IV) and it assesses working memory. It consists of a Digit Span Forward task in which individuals are asked to repeat numbers in the same sequence as they were presented verbally and a Digit Span Backward task in which participants repeat the numbers in the reversed order to which they were heard. Each task yields a score ranging from 0 to 16. Higher scores represent better outcomes for this test. The trajectory of digit span scores during the course of the hospitalization was used to assess improvements in mental status and whether these varied systematically as a function of treatment protocol. Digit span measurements were collected every four hours during waking hours (7AM to 10PM). The measure analyzed is the average linear change in scores between enrollment and either 24-hours or DKA resolution, whichever occurred first.
Measured: 24 hours
Mean Scores on Tests of Memory Capacity 3 Months After Recovery From DKA.
Contextual memory was assessed via color and spatial-position tasks. Color-Task: black-ink items on a white square background were shown on a computer screen with a colored border. Subjects were asked to remember the item and the item's border color. Items were shown for 1 second, followed by a 1-second interval in which a fixation point was shown. Then, subjects were given a self-paced recognition test including studied drawings and new drawings shown in random order with no color border. Subjects determined if they had seen the drawing before. For recognized drawings, subjects reported the previously shown border color. Spatial-Position task: identical to the color task except that the items instead varied in their spatial position on the computer screen. The item-context association rate is the rate of correct item-color and item-spatial position recalled over the total of previously viewed items correctly recognized. Score range: 0-1 with higher scores indicating a better outcome.
Measured: 3 months
Intelligence Quotient (IQ) Testing
IQ was assessed with the WASI (6-18 year olds) or WPPSI-III (3-5 year olds) at the 3 month follow-up visit. The Wechsler Abbreviated Scale of Intelligence (WASI) is a measure of IQ designed for individuals aged 6 to 89. The WASI includes four subtests; the Block Design and Matrix Reasoning tests measure Performance IQ, and the Vocabulary and Similarities tests measure Verbal IQ. Full scale IQ was computed from these scores and used for analyses. Scores typically vary from 75 to 135 with higher scores representing a better outcome.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2011 (estimated)
- Study startNov 2010
- Primary completionSep 2016
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cerebral EdemaStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 1,389 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Nathan Kuppermann, MD, MPH, Principal investigator, University of California, DavisNicole S Glaser, MD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01365793
- Sponsor's protocol ID
- 230233
- Other IDs
- U01HD062417
- Status last verified
- Jun 2018
- First submitted
- 1 Jun 2011
- Last updated
- 25 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23490311
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluid Therapy and Cerebral Injury in Pediatric Diabetic Ketoacidosis
- ClinicalTrials.gov ID
- NCT01365793
- Acronym / sponsor ID
- 230233
- Conditions
- Cerebral Edema, Diabetic Ketoacidosis
- Keywords
- cerebral edema, diabetic ketoacidosis, pediatric diabetes, fluid therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,389 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Nov 2010
- Primary completion
- Sep 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 3 Jun 2011 (estimated)
- Results
- Posted 25 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Rapid rehydration using 0.45% saline replacement fluid | Experimental | Drug: 0.45% saline replacement fluidThis 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. |
| Rapid rehydration using 0.9% saline replacement fluid | Experimental | Drug: 0.9% saline replacement fluidThis 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. |
| Slower rehydration using 0.45% saline intravenous fluid | Experimental | Drug: 0.45% saline intravenous fluidThis arm will involve slower rehydration (assumed 5% fluid deficit and no additional fluid bolus) with 0.45% saline used as the replacement fluid. |
| Slower rehydration using 0.9% saline intravenous fluid | Experimental | Drug: 0.9% saline Intravenous fluidThis arm will involve slower rehydration (assumed 5% fluid deficit and no additional fuid bolus) with 0.9% saline used as the replacement fluid. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- must present or be transferred to a participating emergency department
- age less than 18 years
- diagnosis of DKA
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 0.45% saline replacement fluid10cc/Kg bolus of 0.9% saline followed by 0.45% saline used as the replacement fluid | Drug | Rapid rehydration using 0.45% saline replacement fluid |
| 0.9% saline replacement fluid10cc/Kg bolus of 0.9% saline followed by 0.9% saline used as the replacement fluid. | Drug | Rapid rehydration using 0.9% saline replacement fluid |
| 0.45% saline intravenous fluid0.45% saline fluid | Drug | Slower rehydration using 0.45% saline intravenous fluid |
| 0.9% saline Intravenous fluid0.9% saline fluid | Drug | Slower rehydration using 0.9% saline intravenous fluid |
Primary outcome
the Number of Participants With Glasgow Coma Score (GCS) < 14 Within the First 24 Hours of Treatment for Diabetic Ketoacidosis (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.
4 secondary outcomes
Frequency of Clinically Apparent Brain Injury
Time frame: 24 hours
Hourly Improvement in Forward and Backward Digit Span Scores During DKA Treatment (Mean Difference Per Hour)
Time frame: 24 hours
Mean Scores on Tests of Memory Capacity 3 Months After Recovery From DKA.
Time frame: 3 months
Intelligence Quotient (IQ) Testing
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23490311Glaser 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.
- Official website of the Pediatric Emergency Care Applied Research Network (PECARN), funded by HRSA/MCHBLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nathan Kuppermann, MD, MPH principal investigator
University of California, Davis
Nicole S Glaser, MD principal investigator
University of California, Davis
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 0.45% saline replacement fluid, 0.9% saline replacement fluid and 0.45% saline intravenous fluid in people with Cerebral Edema and Diabetic Ketoacidosis, run by University of California, Davis at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the Number of Participants With Glasgow Coma Score (GCS) < 14 Within the First 24 Hours of Treatment for Diabetic Ketoacidosis (DKA) (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01365793, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2018.