Early Administration of Insulin Glargine in Patients With Diabetic Ketoacidosis

NCT06007508 | Terminated Phase 2 FDA Drug

• 1 other identifier: X1935200
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetic ketoacidosis (DKA) is a medical emergency that is associated with significant morbidity and mortality for both patients with type I and type II diabetes. By correcting hyperglycemia and inhibiting the release of free fatty acids, insulin administration leads to decreased ketone formation and resolution of acidosis. Short-acting intravenous insulin is often preferred to subcutaneous administration for initial management due to its short half-life and ease of titration, but patients will eventually need to transition to subcutaneous insulin prior to discharge. The timing of initiation or resumption of home long-acting subcutaneous insulin is controversial in the treatment of DKA. It is currently unknown if resuming a portion or all of the patient's home basal regimen during the initial treatment phase of DKA will provide an impact on patient care. The purpose of this study is to evaluate the impact of early glargine administration if the patient was not previously on basal insulin or resuming the patient's home basal insulin regimen within two hours after the start of the intravenous insulin infusion in addition to usual care will improve patient outcomes.

Conditions

DKA

Keywords

DKA; Hypoglycemia; Rebound Hyperglycemia; Type 1 Diabetes; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Does early administration of insulin glargine result in a change in ICU length of stay when compared to usual care for the treatment of diabetic ketoacidosis?

  Hypothesis: Early administration of insulin glargine will result in shorter ICU length of stay when compared to usual care in patients with DKA.

  Assessed from time of intervention until discharge from ICU to general medical unit or from hospital, up to 12 weeks

Secondary Outcomes (7)

• Does early administration of insulin glargine result in a change in hospital length of stay (defined as time between start of insulin infusion and discharge from hospital) when compared to usual care for the treatment of diabetic ketoacidosis?

  Until discharge from ICU to general medical unit or from hospital, up to 12 weeks

• Does early administration of insulin glargine result in a change in recovery from DKA when compared to usual care for the treatment of diabetic ketoacidosis?

  Until discharge from ICU to general medical unit or from hospital, up to 12 weeks

• Does early administration of insulin glargine result in a change in duration of time on IV insulin infusion when compared to usual care for the treatment of diabetic ketoacidosis?

  Until discharge from ICU to general medical unit or from hospital, up to 12 weeks

• Does early administration of insulin glargine result in a change in prevalence of rebound hyperglycemia when compared to usual care for the treatment of diabetic ketoacidosis?

  Through 24 hour mark after IV insulin discontinuation

• The number of hypoglycemic (defined as blood glucose < 70mg/dL) events occurring while on IV insulin therapy or in the 24h hours after IV insulin infusion discontinuation with early insulin glargine administration compared to usual care

  Assessed from time of hospitalization until 24 hour mark after IV insulin discontinuation

Study Arms (2)

Standard of Care

NO INTERVENTION

Subjects presenting to ED with diagnosis of DKA and receiving intravenous short acting insulin will not have orders for subcutaneous insulin glargine placed for research purposes.

Intervention

ACTIVE COMPARATOR

Subjects presenting to ED with diagnosis of DKA will receive study medication set to begin within 2 hours after initiation of the IV insulin infusion. The dose will come from IV pharmacy and dispensed in a 1 mL insulin syringe. If the patient was not taking basal insulin prior to admission, the patient will receive 0.2 units/kg insulin glargine. If the patient was taking basal insulin prior to admission, the patient will receive their home insulin glargine dose.

Drug: Insulin Glargine

Interventions

Insulin Glargine DRUG

Long-acting insulin

Also known as: Lantus, Basaglar, Semglee

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presented to Regions Hospital ED for chief complaint of DKA, nausea, vomiting, abdominal pain, hyperglycemia, or similar
• Meets all below diagnostic criteria for DKA per the American Diabetes Association:
• Arterial or venous pH \</= 7.3
• Serum Bicarbonate \</= 18 mEq/L
• Ketonuria or ketonemia
• Anion Gap \> 10
• Blood sugar \> 250 mg/dL
• Receiving IV insulin infusion
• It is feasible to provide insulin glargine within 2 hours (+/- 30 minutes) of IV infusion start
• Will be admitted to the ICU for DKA, or already admitted to the ICU for DKA
• Ability to provide informed consent

You may not qualify if:

• Age \< 18
• End stage renal disease or hepatic disease
• Hypotension requiring IV vasopressors or inotropes at any point during admission (i.e. norepinephrine, dobutamine, vasopressin, etc.)
• Need for emergent surgery
• Pregnant patients
• Prisoners
• Indication for insulin therapy other than DKA (hypertriglyceridemia, beta-blocker overdose, hyperglycemia without DKA)
• Patients receiving prior to admission insulin pump therapy
• Patients receiving prior to admission combination insulin products (i.e. Novolin® 70/30, Novolog® 70/30, Humalog® 75/25, etc.)
• Did not consent to study

Sponsors & Collaborators

• HealthPartners Institute: lead

Study Sites (1)

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Related Publications (8)

• Kitabchi 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.

  PMID: 19564476 BACKGROUND

• Hirsch IB. Insulin analogues. N Engl J Med. 2005 Jan 13;352(2):174-83. doi: 10.1056/NEJMra040832. No abstract available.

  PMID: 15647580 BACKGROUND

• American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019 Jan;42(Suppl 1):S90-S102. doi: 10.2337/dc19-S009.

  PMID: 30559235 BACKGROUND

• Hsia 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.

  PMID: 22685233 BACKGROUND

• Doshi 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.

  PMID: 26013711 BACKGROUND

• Houshyar 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.

  PMID: 26155506 BACKGROUND

• Rappaport SH, Endicott JA, Gilbert MP, Farkas JD, Clouser RD, McMillian WD. A Retrospective Study of Early vs Delayed Home Dose Basal Insulin in the Acute Management of Diabetic Ketoacidosis. J Endocr Soc. 2019 Apr 11;3(5):1079-1086. doi: 10.1210/js.2018-00400. eCollection 2019 May 1.

  PMID: 31069278 BACKGROUND

• Gosmanov AR, Gosmanova EO, Dillard-Cannon E. Management of adult diabetic ketoacidosis. Diabetes Metab Syndr Obes. 2014 Jun 30;7:255-64. doi: 10.2147/DMSO.S50516. eCollection 2014.

  PMID: 25061324 BACKGROUND

MeSH Terms

Conditions

Hypoglycemia; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Interventions

Insulin Glargine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Adis Keric, PharmD

  Regions Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a two arm, prospective, randomized, open label trial in patients presenting with DKA. Block randomization will be used to ensure equal group sizes.

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: August 23, 2023
• Study Start: May 31, 2022
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: June 18, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)