Diabetic KetoacidosisPhase 4NCT04567225
Early Basal Insulin Administration in Adult Diabetic Ketoacidosis Management
A Phase 4 study testing Early Glargine, Late Glargine and IV insulin infusion in people with Diabetic Ketoacidosis and Type 1 Diabetes, run by The Cleveland Clinic at 1 site in United States.
Trial summary
Early Basal Insulin Administration in Adult Diabetic Ketoacidosis Management Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Ketoacidosis, Type 1 Diabetes, Type 2 Diabetes
- What is being tested?
- Early Glargine, Late Glargine and IV insulin infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2020to 27 Aug 2021
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years old
- Meet DKA definition (BG ≥ 250 mg/dl, Anion Gap > 12 mEq/L, and positive Ketones in serum or urine)
- Having the capacity to sign Informed consent
Who cannot join
- IV insulin infusion was initiated for more than 4 hours.
- Persistent hypotension (SBP<80 mmHg despite receiving 1000cc normal saline).
- Require Vasopressor
- Acute Coronary Syndrome
- Pregnant
- End-stage renal disease
Show all 10Show fewer
- Unwilling to consent to participate in the trial
- Currently under police custody
- Transferred from another hospital
- Require emergent surgery
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Fairview Hospital
Cleveland, Ohio, 44111
About this study
Early Basal Insulin Administration in Adult Diabetic Ketoacidosis Management
Read the detailed description
The transition from IV Insulin Infusion (IVII) to Subcutaneous Long-acting insulin injections in Diabetic Ketoacidosis (DKA) management frequently results in rebound hyperglycemia, particularly if there are high insulin requirements that can adversely affect the DKA recovery, increase Length Of Stay (LOS), morbidity, and mortality. Investigators propose a prospective, open-label, intervention, non-randomized, controlled study to test the hypothesis that an insulin glargine dose of 0.4 Units/kg early administered (within four hours) of IVII initiation in DKA management in adult would be effective and safe in shortening the time to anion gap closure comparing to the standard practice.
- Conditions
- Diabetic Ketoacidosis, Type 1 Diabetes, Type 2 Diabetes
- Being tested
- Early Glargine, Late Glargine, IV insulin infusion, IV fluid and electrolytes replacement
- Medical subject headings
- Diabetic Ketoacidosis, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early GlargineDrug
Also called lantus
A dose of insulin glargine, 0.4 unit/kg, will be given within 4 hours from initiating the IV Insulin Infusion
Late GlargineDrug
Also called lantus
A historical retrospective control group for the adult patients admitted to the same ICU with a diagnosis of DKA and received insulin glargine after anion gap closure.
IV insulin infusionOther
Continuous weight based IV insulin infusion as per Cleveland Clinic DKA Protocol
IV fluid and electrolytes replacementOther
The IV fluid and electrolytes replacement will be left to the treating physician's discretion. IV fluid to contain dextrose to keep Target Blood Glucose 150 - 200 mg/dl during the DKA management and 140 - 180 mg/dl after DKA resolution.
| Study group | Role | What they receive |
|---|---|---|
| Early Glargine | Experimental | All consecutive adult patients getting admitted to Medical ICU and meet the inclusion criteria and accepted to receive insulin glargine early as per the protocol. They will receive insulin glargine 0.4 unit/kg within 4 hours from initiating the IV Insulin Infusion, as per the Cleveland Clinic DKA protocol. Receives: Drug: Early Glargine; Other: IV insulin infusion; Other: IV fluid and electrolytes replacement |
| Standard practice (Late Glargine) | Active comparator | Retrospective, prespecified and matched sample of consecutive adults who admitted to the same Medical ICU with a diagnosis of DKA in the period between January 1st 2019 till the Institutional Review Board (IRB) approval date and didn't receive basal insulin before Anion Gap closure. Receives: Drug: Late Glargine; Other: IV insulin infusion; Other: IV fluid and electrolytes replacement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Anion Gap Closure
Measured in hours from starting insulin infusion till anion gap ≤ 12 milliequivalent/Liter (mEq/L)
Measured: Participants monitored from hospital admission to discharge, an average of 5 days
Secondary outcomes (6)
Hospital Length of Stay
The time, in days, from the patient admission to the hospital till discharge
Measured: Participants monitored from hospital admission to discharge, an average of 5 days
ICU Length of Stay
The time, in hours, from the patient admission to the ICU till transfer to regular nursing floor
Measured: Participants monitored from hospital admission to discharge, an average of 5 days
Total IV Insulin Infusion Dose
the total amount of insulin infusion, by International Unit, has been received by the patient during the DKA treatment
Measured: Participants monitored from hospital admission to discharge, an average of 5 days
Incidence of Transitional Failure
Defined as the recurrence of DKA (BG ≥ 250 mg/dl, Anion Gap > 12 milliequivalent/Liter (mEq/L), and positive Ketones in serum or urine) after initial IV insulin infusion (IVII) discontinuation within 24 hours and requiring re-initiating the IVII
Measured: up to 24 hours after IVII discontinuation
Incidence of Hyperglycemia
Incidence of hyperglycemia (> 180 mg/dL) after IVII discontinuation
Measured: up to 24 hours after initial Insulin Glargine dose
Incidence of Hypoglycemia
Incidence of hypoglycemia (defined as ≤ 70 mg/dL, <54 mg/dL, <40 mg/dl) after IVII discontinuation
Measured: up to 24 hours after initial Insulin Glargine dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2020
- Study start1 Oct 2020
- Primary completion27 Aug 2021
- Study completion27 Aug 2021
Why it stopped: Stopped after internal review
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 (8)Papers the sponsor has linked to this study.
- Other trials for Diabetic KetoacidosisStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohammed Al-Jaghbeer, The Cleveland Clinic
- Investigators
- Mohammed Al jaghbeer, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04567225
- Sponsor's protocol ID
- 20-903
- Status last verified
- Aug 2022
- First submitted
- 23 Sep 2020
- Last updated
- 21 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual subject results will not be shared with those involved in the prospective arm
Publications
Realsen J, Goettle H, Chase HP. Morbidity and mortality of diabetic ketoacidosis with and without insulin pump care. Diabetes Technol Ther. 2012 Dec;14(12):1149-54. doi: 10.1089/dia.2012.0161. Epub 2012 Sep 25.
PubMed 23009106Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43. doi: 10.2337/dc09-9032. No abstract available.
PubMed 19564476Bunn S, Halm M. Long-Acting Insulin on the Road to Recovery With Diabetic Ketoacidosis. Am J Crit Care. 2016 May;25(3):277-80. doi: 10.4037/ajcc2016681. No abstract available.
PubMed 27134235Hsia E, Seggelke S, Gibbs J, Hawkins RM, Cohlmia E, Rasouli N, Wang C, Kam I, Draznin B. Subcutaneous administration of glargine to diabetic patients receiving insulin infusion prevents rebound hyperglycemia. J Clin Endocrinol Metab. 2012 Sep;97(9):3132-7. doi: 10.1210/jc.2012-1244. Epub 2012 Jun 8.
PubMed 22685233Savage MW, Dhatariya KK, Kilvert A, Rayman G, Rees JA, Courtney CH, Hilton L, Dyer PH, Hamersley MS; Joint British Diabetes Societies. Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabet Med. 2011 May;28(5):508-15. doi: 10.1111/j.1464-5491.2011.03246.x.
PubMed 21255074Doshi P, Potter AJ, De Los Santos D, Banuelos R, Darger BF, Chathampally Y. Prospective randomized trial of insulin glargine in acute management of diabetic ketoacidosis in the emergency department: a pilot study. Acad Emerg Med. 2015 Jun;22(6):657-62. doi: 10.1111/acem.12673. Epub 2015 May 25.
PubMed 26013711Houshyar J, Bahrami A, Aliasgarzadeh A. Effectiveness of Insulin Glargine on Recovery of Patients with Diabetic Ketoacidosis: A Randomized Controlled Trial. J Clin Diagn Res. 2015 May;9(5):OC01-5. doi: 10.7860/JCDR/2015/12005.5883. Epub 2015 May 1.
PubMed 26155506Shankar V, Haque A, Churchwell KB, Russell W. Insulin glargine supplementation during early management phase of diabetic ketoacidosis in children. Intensive Care Med. 2007 Jul;33(7):1173-1178. doi: 10.1007/s00134-007-0674-3. Epub 2007 May 17.
PubMed 17508198
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Basal Insulin Administration in Adult Diabetic Ketoacidosis Management
- ClinicalTrials.gov ID
- NCT04567225
- Acronym / sponsor ID
- 20-903
- Conditions
- Diabetic Ketoacidosis, Type 1 Diabetes, Type 2 Diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Stopped after internal review
- Enrolment
- 39 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 27 Aug 2021 (actual)
- Study completion
- 27 Aug 2021 (actual)
- First posted
- 28 Sep 2020 (actual)
- Results
- Posted 25 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Early Basal Insulin Administration in Adult Diabetic Ketoacidosis Management
Detailed description
The transition from IV Insulin Infusion (IVII) to Subcutaneous Long-acting insulin injections in Diabetic Ketoacidosis (DKA) management frequently results in rebound hyperglycemia, particularly if there are high insulin requirements that can adversely affect the DKA recovery, increase Length Of Stay (LOS), morbidity, and mortality. Investigators propose a prospective, open-label, intervention, non-randomized, controlled study to test the hypothesis that an insulin glargine dose of 0.4 Units/kg early administered (within four hours) of IVII initiation in DKA management in adult would be effective and safe in shortening the time to anion gap closure comparing to the standard practice.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early Glargine | Experimental | Drug: Early Glargine, Other: IV insulin infusion, Other: IV fluid and electrolytes replacementAll consecutive adult patients getting admitted to Medical ICU and meet the inclusion criteria and accepted to receive insulin glargine early as per the protocol. They will receive insulin glargine 0.4 unit/kg within 4 hours from initiating the IV Insulin Infusion, as per the Cleveland Clinic DKA protocol. |
| Standard practice (Late Glargine) | Active comparator | Drug: Late Glargine, Other: IV insulin infusion, Other: IV fluid and electrolytes replacementRetrospective, prespecified and matched sample of consecutive adults who admitted to the same Medical ICU with a diagnosis of DKA in the period between January 1st 2019 till the Institutional Review Board (IRB) approval date and didn't receive basal insulin before Anion Gap closure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥ 18 years old
- Meet DKA definition (BG ≥ 250 mg/dl, Anion Gap > 12 mEq/L, and positive Ketones in serum or urine)
- Having the capacity to sign Informed consent
Key exclusion criteria (10 listed)
- IV insulin infusion was initiated for more than 4 hours.
- Persistent hypotension (SBP<80 mmHg despite receiving 1000cc normal saline).
- Require Vasopressor
- Acute Coronary Syndrome
- Pregnant
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 |
|---|---|---|
| Early GlargineAlso: lantusA dose of insulin glargine, 0.4 unit/kg, will be given within 4 hours from initiating the IV Insulin Infusion | Drug | Early Glargine |
| Late GlargineAlso: lantusA historical retrospective control group for the adult patients admitted to the same ICU with a diagnosis of DKA and received insulin glargine after anion gap closure. | Drug | Standard practice (Late Glargine) |
| IV insulin infusionContinuous weight based IV insulin infusion as per Cleveland Clinic DKA Protocol | Other | Early Glargine, Standard practice (Late Glargine) |
| IV fluid and electrolytes replacementThe IV fluid and electrolytes replacement will be left to the treating physician's discretion. IV fluid to contain dextrose to keep Target Blood Glucose 150 - 200 mg/dl during the DKA management and 140 - 180 mg/dl after DKA resolution. | Other | Early Glargine, Standard practice (Late Glargine) |
Primary outcome
Time to Anion Gap Closure
Time frame: Participants monitored from hospital admission to discharge, an average of 5 days
Measured in hours from starting insulin infusion till anion gap ≤ 12 milliequivalent/Liter (mEq/L)
6 secondary outcomes
Hospital Length of Stay
Time frame: Participants monitored from hospital admission to discharge, an average of 5 days
ICU Length of Stay
Time frame: Participants monitored from hospital admission to discharge, an average of 5 days
Total IV Insulin Infusion Dose
Time frame: Participants monitored from hospital admission to discharge, an average of 5 days
Incidence of Transitional Failure
Time frame: up to 24 hours after IVII discontinuation
Incidence of Hyperglycemia
Time frame: up to 24 hours after initial Insulin Glargine dose
Incidence of Hypoglycemia
Time frame: up to 24 hours after initial Insulin Glargine dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23009106Realsen J, Goettle H, Chase HP. Morbidity and mortality of diabetic ketoacidosis with and without insulin pump care. Diabetes Technol Ther. 2012 Dec;14(12):1149-54. doi: 10.1089/dia.2012.0161. Epub 2012 Sep 25.
- Background: PubMed 19564476Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43. doi: 10.2337/dc09-9032. No abstract available.
- Background: PubMed 27134235Bunn S, Halm M. Long-Acting Insulin on the Road to Recovery With Diabetic Ketoacidosis. Am J Crit Care. 2016 May;25(3):277-80. doi: 10.4037/ajcc2016681. No abstract available.
- Background: PubMed 22685233Hsia E, Seggelke S, Gibbs J, Hawkins RM, Cohlmia E, Rasouli N, Wang C, Kam I, Draznin B. Subcutaneous administration of glargine to diabetic patients receiving insulin infusion prevents rebound hyperglycemia. J Clin Endocrinol Metab. 2012 Sep;97(9):3132-7. doi: 10.1210/jc.2012-1244. Epub 2012 Jun 8.
- Background: PubMed 21255074Savage MW, Dhatariya KK, Kilvert A, Rayman G, Rees JA, Courtney CH, Hilton L, Dyer PH, Hamersley MS; Joint British Diabetes Societies. Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabet Med. 2011 May;28(5):508-15. doi: 10.1111/j.1464-5491.2011.03246.x.
- Background: PubMed 26013711Doshi P, Potter AJ, De Los Santos D, Banuelos R, Darger BF, Chathampally Y. Prospective randomized trial of insulin glargine in acute management of diabetic ketoacidosis in the emergency department: a pilot study. Acad Emerg Med. 2015 Jun;22(6):657-62. doi: 10.1111/acem.12673. Epub 2015 May 25.
- Background: PubMed 26155506Houshyar J, Bahrami A, Aliasgarzadeh A. Effectiveness of Insulin Glargine on Recovery of Patients with Diabetic Ketoacidosis: A Randomized Controlled Trial. J Clin Diagn Res. 2015 May;9(5):OC01-5. doi: 10.7860/JCDR/2015/12005.5883. Epub 2015 May 1.
- Background: PubMed 17508198Shankar V, Haque A, Churchwell KB, Russell W. Insulin glargine supplementation during early management phase of diabetic ketoacidosis in children. Intensive Care Med. 2007 Jul;33(7):1173-1178. doi: 10.1007/s00134-007-0674-3. Epub 2007 May 17.
- Individual participant dataSharing planned: No. Individual subject results will not be shared with those involved in the prospective arm
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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.
Mohammed Al jaghbeer, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Early Glargine, Late Glargine and IV insulin infusion in people with Diabetic Ketoacidosis and Type 1 Diabetes, run by The Cleveland Clinic at 1 site 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 3 inclusion and 10 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: stopped early, as of the sponsor's last update on 21 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Aug 2022). 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?
Time to Anion Gap Closure (time frame: Participants monitored from hospital admission to discharge, an average of 5 days). 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 NCT04567225, which also lists 8 linked publications.
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 21 Sep 2022.